1. Inducible nitric oxide synthase (iNOS) is involved in inflammatory processes by synthesizing nitric oxide (NO) in response to stimuli like cytokines.
2. In periodontitis, proinflammatory cytokines stimulate iNOS production in immune and epithelial cells, leading to increased NO levels that can have both protective and pathological effects.
3. NO may function to control bacterial growth and bone resorption, but excessive NO production can cause tissue damage through oxidative and nitrosative reactions.
Says about most important free radicals and main physiologic roles of free radicals(on transduction and transcriptional gene factors), about stress oxidative , effects of stress oxidative on some common cochlear anthologies and its related processes
Researchers from Canada and Mexico studied the oxidation of o-isopropylphenol using lead tetraacetate, which produced a dienone acetate. This dienone acetate can dimerize and represents a core structure found in natural celastroidin terpenes from the plant Hippocratea Celastroides. Using various analytical techniques, the researchers identified six oxidation products, including the dienolone acetate and two dimer structures. Comparing the synthetic and natural product dimers, they determined that the natural product dimer corresponded to the photochemical pathway product, while the synthetic dimer had the opposite geometry, as confirmed by molecular modeling. Oxidation of o-cresol produced similar products.
Response and tolerance strategies of microorganisms to oxidativeKumar Purushotam
Microorganisms have developed various response and tolerance strategies to deal with oxidative stress caused by reactive oxygen species (ROS). These strategies include antioxidant enzymes like superoxide dismutase, catalase, and peroxidase that break down ROS. Microbes also induce genes encoding these enzymes and other stress response proteins through regulatory systems like SoxRS and OxyR in E. coli. Different groups of microbes utilize strategies like glutathione, mycothiol, efflux pumps, DNA repair, and avoidance mechanisms to tolerate oxidative stress.
Nitric oxide synthases (NOS) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. There are three main types of NOS - neuronal NOS, inducible NOS, and endothelial NOS - located in different tissues and performing different functions. NOS is a heme-containing dimerized protein that uses NADPH, FAD, FMN, tetrahydrobiopterin, and heme as cofactors. It converts L-arginine to citrulline and NO in a two-domain reaction involving the transfer of electrons from the reductase domain to the oxygenase domain. NOS and NO play important roles in many physiological processes and human diseases
This document discusses reactive oxygen species (ROS) and antioxidants in biology and medicine. It defines key terms and explores the origins and effects of different ROS like superoxide, nitric oxide, and hydroxyl radicals. It also examines the mechanisms of tissue damage caused by ROS and the roles of antioxidant defense systems in preventing damage. Biomarkers of oxidative stress and lipid, DNA, and protein damage are reviewed. Evidence suggests ROS contribute to periodontal tissue destruction in periodontitis through lipid peroxidation and oxidative damage.
Reactive oxygen species (ROS) are produced during normal cellular processes and can act as signaling molecules by modifying receptors and proteins involved in cell signaling pathways. However, excessive ROS production causes oxidative stress and damage to lipids, proteins and DNA. ROS signaling is involved in processes like cell proliferation, apoptosis, and inflammatory responses through receptors like cytokine receptors, receptor tyrosine kinases, and G-protein coupled receptors. While low levels of ROS function in cell signaling, high levels contribute to disease states like cancer, neurodegeneration and cardiovascular diseases.
Oxidative stress occurs when there is an imbalance between reactive oxygen species and antioxidants in the body, leading to oxidative damage of DNA, proteins, and lipids. It has been implicated in aging and many diseases such as atherosclerosis, rheumatoid arthritis, and cancers. Antioxidants like vitamins A, C, E, and enzymes including superoxide dismutase, catalase, and the glutathione system help combat oxidative stress. The glutathione system consists of glutathione, NADPH, and related enzymes that are essential for its proper function. Glucose-6-phosphate dehydrogenase deficiency can impair the glutathione system.
Free radicals are unstable molecules that can damage cells. They are produced through normal cell processes and external factors like pollution and smoking. Reactive oxygen species (ROS) are a type of free radical involving oxygen. ROS can damage DNA and proteins, contributing to cancer development. ROS also cause oxidative stress, an imbalance that promotes carcinogenesis. Antioxidants may help prevent cancer by reducing oxidative stress, though some research indicates controlled oxidative stress through substances like vitamin C can also fight tumors. Curcumin in turmeric has shown anti-cancer effects by down-regulating inflammatory genes and enzymes linked to cancer.
Says about most important free radicals and main physiologic roles of free radicals(on transduction and transcriptional gene factors), about stress oxidative , effects of stress oxidative on some common cochlear anthologies and its related processes
Researchers from Canada and Mexico studied the oxidation of o-isopropylphenol using lead tetraacetate, which produced a dienone acetate. This dienone acetate can dimerize and represents a core structure found in natural celastroidin terpenes from the plant Hippocratea Celastroides. Using various analytical techniques, the researchers identified six oxidation products, including the dienolone acetate and two dimer structures. Comparing the synthetic and natural product dimers, they determined that the natural product dimer corresponded to the photochemical pathway product, while the synthetic dimer had the opposite geometry, as confirmed by molecular modeling. Oxidation of o-cresol produced similar products.
Response and tolerance strategies of microorganisms to oxidativeKumar Purushotam
Microorganisms have developed various response and tolerance strategies to deal with oxidative stress caused by reactive oxygen species (ROS). These strategies include antioxidant enzymes like superoxide dismutase, catalase, and peroxidase that break down ROS. Microbes also induce genes encoding these enzymes and other stress response proteins through regulatory systems like SoxRS and OxyR in E. coli. Different groups of microbes utilize strategies like glutathione, mycothiol, efflux pumps, DNA repair, and avoidance mechanisms to tolerate oxidative stress.
Nitric oxide synthases (NOS) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. There are three main types of NOS - neuronal NOS, inducible NOS, and endothelial NOS - located in different tissues and performing different functions. NOS is a heme-containing dimerized protein that uses NADPH, FAD, FMN, tetrahydrobiopterin, and heme as cofactors. It converts L-arginine to citrulline and NO in a two-domain reaction involving the transfer of electrons from the reductase domain to the oxygenase domain. NOS and NO play important roles in many physiological processes and human diseases
This document discusses reactive oxygen species (ROS) and antioxidants in biology and medicine. It defines key terms and explores the origins and effects of different ROS like superoxide, nitric oxide, and hydroxyl radicals. It also examines the mechanisms of tissue damage caused by ROS and the roles of antioxidant defense systems in preventing damage. Biomarkers of oxidative stress and lipid, DNA, and protein damage are reviewed. Evidence suggests ROS contribute to periodontal tissue destruction in periodontitis through lipid peroxidation and oxidative damage.
Reactive oxygen species (ROS) are produced during normal cellular processes and can act as signaling molecules by modifying receptors and proteins involved in cell signaling pathways. However, excessive ROS production causes oxidative stress and damage to lipids, proteins and DNA. ROS signaling is involved in processes like cell proliferation, apoptosis, and inflammatory responses through receptors like cytokine receptors, receptor tyrosine kinases, and G-protein coupled receptors. While low levels of ROS function in cell signaling, high levels contribute to disease states like cancer, neurodegeneration and cardiovascular diseases.
Oxidative stress occurs when there is an imbalance between reactive oxygen species and antioxidants in the body, leading to oxidative damage of DNA, proteins, and lipids. It has been implicated in aging and many diseases such as atherosclerosis, rheumatoid arthritis, and cancers. Antioxidants like vitamins A, C, E, and enzymes including superoxide dismutase, catalase, and the glutathione system help combat oxidative stress. The glutathione system consists of glutathione, NADPH, and related enzymes that are essential for its proper function. Glucose-6-phosphate dehydrogenase deficiency can impair the glutathione system.
Free radicals are unstable molecules that can damage cells. They are produced through normal cell processes and external factors like pollution and smoking. Reactive oxygen species (ROS) are a type of free radical involving oxygen. ROS can damage DNA and proteins, contributing to cancer development. ROS also cause oxidative stress, an imbalance that promotes carcinogenesis. Antioxidants may help prevent cancer by reducing oxidative stress, though some research indicates controlled oxidative stress through substances like vitamin C can also fight tumors. Curcumin in turmeric has shown anti-cancer effects by down-regulating inflammatory genes and enzymes linked to cancer.
Role of Oxidative stress in disease modificationSoobiya Majeed
This presentation discusses the role of oxidative stress in disease modification. It defines oxidative stress as an imbalance between reactive oxygen species and a biological system's ability to detoxify them or repair damage. It discusses how free radicals accumulate and damage cells, DNA, lipids, sugars, and proteins. This can lead to dysfunction, damage, enzyme reactivation, and protein re-modification, resulting in aging and diseases. It provides Parkinson's disease, cancer, and cardiac failure as examples of diseases related to oxidative stress and discusses antioxidants as a way to prevent, intercept, or repair damage from free radicals. The conclusion emphasizes that oxidative stress underlies many diseases by generating reactive metabolites that overwhelm antioxidant defenses.
Use RT2 Profiler PCR Arrays to profile gene expression of key
regulators and effectors of necrosis, apoptosis, and autophagy pathways in
cells treated with oxidative stress inducers vs untreated controls.
Compare expression profiles to identify differentially expressed genes that
may determine cell fate decision under oxidative stress.
The Role Of Transition Metals & Reactive Oxygen Species (ROS) In Alzheimer's ...Pırıl Erel
This powerpoint discusses the role of transition metals and amyloid plaque formation in Alzheimer’s disease (AD) and how metal ion chelators may be employed as therapeutic agents for AD. It describes the disorder, how it progresses and what happens to the brain tissue.
Furthermore, within the presentation I describe a drug which chelates metals including a description about the chemical formulation of these drugs and how the drug can be preventative of AD.
The document summarizes key steps in nitrate assimilation by plants. It discusses how plants reduce nitrate to nitrite and then to ammonium within cells. The ammonium is assimilated through the glutamine synthetase/glutamate synthase pathway to produce glutamine and other organic nitrogen compounds. Biological nitrogen fixation by symbiotic bacteria is also summarized, including the signaling and nodulation processes that allow nitrogen-fixing bacteria to interact with plant hosts.
Oxidative Stress in Aging and Human Diseases - Exploring the MechanismsQIAGEN
Many modern diseases, including cancer, cardiovascular disease, diabetes, liver disease, arthritis and neurodegenerative disease are related to aging, and aging is closely linked to oxidative stress. Intensive research is being conducted to understand the antioxidant defense mechanism, the mechanisms of aging itself, as well as their roles in human diseases. This slidedeck provides an update on how oxidative stress is linked to aging and how inflammation leads to aging through DNA damage, telomere dysfunction, cellular senescence and oxidative stress. Recent progress on the health benefits of antioxidants and examination of their potential mechanisms in the prevention and treatment of chronic diseases are also covered. Various assay technologies to tackle the complex signaling pathways in this process will be introduced. Learn how you can apply these advanced tools to your research!
This document provides an overview of gasotransmitters and their role in autoimmune and inflammatory rheumatic diseases (AIRD). It discusses the history and discovery of nitric oxide, carbon monoxide, and hydrogen sulfide as endogenous gas signaling molecules. Specifically regarding carbon monoxide, it describes its production via heme oxygenase enzymes, mechanisms of action through binding metalloproteins like soluble guanylate cyclase, and anti-inflammatory effects in macrophages, dendritic cells, and T-cells by inhibiting maturation and reducing proinflammatory cytokine production while increasing anti-inflammatory IL-10. The document suggests carbon monoxide may downregulate immune responses and thus play a role in preventing autoimmunity.
Free radicals are highly reactive molecules that are produced through normal cell metabolism and environmental exposures. They can damage cells by reacting with lipids, proteins, and DNA if produced in excess. The body has antioxidant defenses like enzymes and nutrients that neutralize free radicals. However, oxidative stress occurs when there is an imbalance between free radical production and antioxidant defenses, leading to chronic diseases. While free radicals play beneficial roles in small amounts for immune function, too many can contribute to conditions like cancer, cardiovascular disease, neurological disorders, and more.
This document defines oxidative stress as an imbalance between reactive oxygen species and antioxidants in cells. It describes how reactive oxygen species are naturally produced through processes like oxidative phosphorylation but can also come from external sources like pollution. The document lists some common reactive oxygen and nitrogen species and endogenous and exogenous antioxidants. It explains that damage from oxidative stress can lead to diseases like atherosclerosis, cancer, and cardiovascular diseases.
Hydrogen sulphide as a gasotransmitter loadingsoorajben10
1. Hydrogen sulfide (H2S) exists in an ionized form as HS- and as "bound sulfur" incorporated into proteins.
2. H2S signaling occurs through protein sulfhydration, the addition of sulfur to cysteine residues, altering protein function. This is more prevalent than nitric oxide protein nitrosylation.
3. H2S relaxes blood vessels by opening ATP-sensitive potassium channels on endothelial cells via channel sulfhydration, causing hyperpolarization.
Free radicals are molecules with unpaired electrons that are highly reactive. They are generated through oxidative metabolism and reactions involving oxygen. Common free radicals include superoxide, hydroxyl radicals, and lipid peroxyl radicals. While free radicals can cause damage to tissues, the body has antioxidant defenses like superoxide dismutase, catalase, glutathione peroxidase, and vitamins C and E that help neutralize free radicals. Antioxidants protect cells from the harmful effects of free radical formation and oxidative stress.
Peer Review of Synergistic Effects of Pesticides and Metals in Parkinson'sAfonte4
The document summarizes research into how certain pesticides and metals can accelerate the formation of fibrils made of the protein alpha-synuclein, which are implicated in Parkinson's disease. The researchers found that some common pesticides like rotenone and DDT, as well as metals like aluminum, iron, and manganese, can induce a conformational change in alpha-synuclein that makes it more prone to aggregate into fibrils. They also observed a synergistic effect between certain pesticides and metals, where together the agents had a much greater accelerating effect on fibril formation than individually. The findings suggest environmental toxins that cause alpha-synuclein misfolding and aggregation may contribute
Oxidative stress is described as the imbalance between pro-oxidants (Reactive oxygen species) and antioxidants levels commonly called redox imbalance. It occurs in a discrete step-wise process of initiation, propagation, and termination stages via the generation of free radicals. These steps bring about effects that have contributed to hypertension through endothelial dysfunction, reduced bioavailability of Nitric oxide, atherosclerotic plaque formation, and reduction of toxic oxidants. Hence, oxidative stress mechanism is implicated in hypertension and thus, the daily intake of antioxidants-containing foods and products to supplement depleted endogenous antioxidants is recommended.
The document discusses oxidative stress and reactive oxygen species (ROS). It defines ROS and lists some examples like superoxide anion radical, hydroxyl radical, and hydrogen peroxide. It describes how ROS are produced endogenously through processes like mitochondrial electron transport, and exogenously through factors like pollution, radiation, and xenobiotics. The effects of ROS include DNA damage and modulation of signal transduction pathways. It also discusses antioxidants, dividing them into antioxidant enzymes like superoxide dismutase and catalase, chain breaking antioxidants like vitamins C and E, and transition metal binding proteins.
Free radicals are unstable molecules that can damage cells. This document discusses free radicals, how they are produced in the body, and how they damage lipids, proteins, and DNA through oxidation. It also describes biomarkers that are used to measure free radical damage, such as markers of lipid peroxidation (MDA, HNE), protein oxidation (protein carbonyls), and DNA oxidation (8-OHdG). Antioxidants in the body help neutralize free radicals and prevent oxidative damage.
Nitric oxide (NO) is a gas that acts as a signaling molecule in various physiological processes. It is produced by nitric oxide synthase enzymes from arginine and oxygen. NO signals the dilation of blood vessels by diffusing into endothelial cells and increasing cGMP levels, which leads to smooth muscle relaxation. It also prevents platelet aggregation, acts as a neurotransmitter, and is involved in the immune response by assisting macrophages in killing bacteria. While NO is important for many functions, too much or too little production can be harmful and lead to conditions like hypertension or infection.
nitrogen is the most abundant atmospheric gas,yet is a limiting factor. this presentation is a bird's eye view, of nitrogen cycle, its fixation, uptake and assimilation in plants
Nitric oxide synthases (NOS) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. There are three main types of NOS - neuronal NOS, inducible NOS, and endothelial NOS - located in different tissues and performing different functions. NOS is a heme-containing dimerized protein that uses NADPH, FAD, FMN, tetrahydrobiopterin, and heme as cofactors. It converts L-arginine to citrulline and NO via a two-domain mechanism involving electron transfer from the reductase domain to the oxygenase domain. Due to its importance in various physiological processes, NOS and NO signaling have been
This document describes a study that compared the antioxidative and anti-inflammatory effects of Taraxacum officinale (common dandelion) methanol extract (TOME) and water extract (TOWE) in lipopolysaccharide-stimulated RAW 264.7 cells. The extracts reduced nitric oxide production and restored depleted glutathione levels and antioxidant enzyme activities. Both extracts also inhibited lipopolysaccharide-induced inducible nitric oxide synthase gene expression and nuclear factor-κB activation. TOME showed more potent effects than TOWE, which was attributed to its higher phenol, luteolin, and chicoric acid content. The results suggest the extracts inhibit oxidative stress and inflammation by elevating antioxidant enzymes and suppressing
This document summarizes reactive oxygen species (ROS) and their role in periodontal disease. It begins by defining antioxidants, free radicals, and oxidative stress. It describes the various ROS like superoxide, hydroxyl radical, nitric oxide, and peroxynitrite. It outlines the sources of free radicals including internal sources like mitochondria and external sources like smoking. It details the effects of ROS on lipids, proteins, DNA and tissues. This causes cellular injury and death. Evidence shows elevated ROS in periodontal disease tissues and its role in tissue damage by affecting gingival cells, bone, ground substance, and collagen. The document also discusses antioxidant defense systems in the body like vitamins C and E, carotenoids,
Nitric oxide (NO) is produced in the body by nitric oxide synthase (NOS) enzymes from the amino acid L-arginine. NO acts as both an intracellular and extracellular signaling molecule and is involved in many physiological processes like neurotransmission and smooth muscle relaxation. There are three isoforms of NOS - neuronal NOS, inducible NOS, and endothelial NOS. NO stimulates soluble guanylate cyclase which increases cyclic GMP levels and triggers smooth muscle relaxation. In addition to cGMP signaling, NO can also signal through S-nitrosylation of proteins or by forming nitrite and nitrate storage pools.
Role of Oxidative stress in disease modificationSoobiya Majeed
This presentation discusses the role of oxidative stress in disease modification. It defines oxidative stress as an imbalance between reactive oxygen species and a biological system's ability to detoxify them or repair damage. It discusses how free radicals accumulate and damage cells, DNA, lipids, sugars, and proteins. This can lead to dysfunction, damage, enzyme reactivation, and protein re-modification, resulting in aging and diseases. It provides Parkinson's disease, cancer, and cardiac failure as examples of diseases related to oxidative stress and discusses antioxidants as a way to prevent, intercept, or repair damage from free radicals. The conclusion emphasizes that oxidative stress underlies many diseases by generating reactive metabolites that overwhelm antioxidant defenses.
Use RT2 Profiler PCR Arrays to profile gene expression of key
regulators and effectors of necrosis, apoptosis, and autophagy pathways in
cells treated with oxidative stress inducers vs untreated controls.
Compare expression profiles to identify differentially expressed genes that
may determine cell fate decision under oxidative stress.
The Role Of Transition Metals & Reactive Oxygen Species (ROS) In Alzheimer's ...Pırıl Erel
This powerpoint discusses the role of transition metals and amyloid plaque formation in Alzheimer’s disease (AD) and how metal ion chelators may be employed as therapeutic agents for AD. It describes the disorder, how it progresses and what happens to the brain tissue.
Furthermore, within the presentation I describe a drug which chelates metals including a description about the chemical formulation of these drugs and how the drug can be preventative of AD.
The document summarizes key steps in nitrate assimilation by plants. It discusses how plants reduce nitrate to nitrite and then to ammonium within cells. The ammonium is assimilated through the glutamine synthetase/glutamate synthase pathway to produce glutamine and other organic nitrogen compounds. Biological nitrogen fixation by symbiotic bacteria is also summarized, including the signaling and nodulation processes that allow nitrogen-fixing bacteria to interact with plant hosts.
Oxidative Stress in Aging and Human Diseases - Exploring the MechanismsQIAGEN
Many modern diseases, including cancer, cardiovascular disease, diabetes, liver disease, arthritis and neurodegenerative disease are related to aging, and aging is closely linked to oxidative stress. Intensive research is being conducted to understand the antioxidant defense mechanism, the mechanisms of aging itself, as well as their roles in human diseases. This slidedeck provides an update on how oxidative stress is linked to aging and how inflammation leads to aging through DNA damage, telomere dysfunction, cellular senescence and oxidative stress. Recent progress on the health benefits of antioxidants and examination of their potential mechanisms in the prevention and treatment of chronic diseases are also covered. Various assay technologies to tackle the complex signaling pathways in this process will be introduced. Learn how you can apply these advanced tools to your research!
This document provides an overview of gasotransmitters and their role in autoimmune and inflammatory rheumatic diseases (AIRD). It discusses the history and discovery of nitric oxide, carbon monoxide, and hydrogen sulfide as endogenous gas signaling molecules. Specifically regarding carbon monoxide, it describes its production via heme oxygenase enzymes, mechanisms of action through binding metalloproteins like soluble guanylate cyclase, and anti-inflammatory effects in macrophages, dendritic cells, and T-cells by inhibiting maturation and reducing proinflammatory cytokine production while increasing anti-inflammatory IL-10. The document suggests carbon monoxide may downregulate immune responses and thus play a role in preventing autoimmunity.
Free radicals are highly reactive molecules that are produced through normal cell metabolism and environmental exposures. They can damage cells by reacting with lipids, proteins, and DNA if produced in excess. The body has antioxidant defenses like enzymes and nutrients that neutralize free radicals. However, oxidative stress occurs when there is an imbalance between free radical production and antioxidant defenses, leading to chronic diseases. While free radicals play beneficial roles in small amounts for immune function, too many can contribute to conditions like cancer, cardiovascular disease, neurological disorders, and more.
This document defines oxidative stress as an imbalance between reactive oxygen species and antioxidants in cells. It describes how reactive oxygen species are naturally produced through processes like oxidative phosphorylation but can also come from external sources like pollution. The document lists some common reactive oxygen and nitrogen species and endogenous and exogenous antioxidants. It explains that damage from oxidative stress can lead to diseases like atherosclerosis, cancer, and cardiovascular diseases.
Hydrogen sulphide as a gasotransmitter loadingsoorajben10
1. Hydrogen sulfide (H2S) exists in an ionized form as HS- and as "bound sulfur" incorporated into proteins.
2. H2S signaling occurs through protein sulfhydration, the addition of sulfur to cysteine residues, altering protein function. This is more prevalent than nitric oxide protein nitrosylation.
3. H2S relaxes blood vessels by opening ATP-sensitive potassium channels on endothelial cells via channel sulfhydration, causing hyperpolarization.
Free radicals are molecules with unpaired electrons that are highly reactive. They are generated through oxidative metabolism and reactions involving oxygen. Common free radicals include superoxide, hydroxyl radicals, and lipid peroxyl radicals. While free radicals can cause damage to tissues, the body has antioxidant defenses like superoxide dismutase, catalase, glutathione peroxidase, and vitamins C and E that help neutralize free radicals. Antioxidants protect cells from the harmful effects of free radical formation and oxidative stress.
Peer Review of Synergistic Effects of Pesticides and Metals in Parkinson'sAfonte4
The document summarizes research into how certain pesticides and metals can accelerate the formation of fibrils made of the protein alpha-synuclein, which are implicated in Parkinson's disease. The researchers found that some common pesticides like rotenone and DDT, as well as metals like aluminum, iron, and manganese, can induce a conformational change in alpha-synuclein that makes it more prone to aggregate into fibrils. They also observed a synergistic effect between certain pesticides and metals, where together the agents had a much greater accelerating effect on fibril formation than individually. The findings suggest environmental toxins that cause alpha-synuclein misfolding and aggregation may contribute
Oxidative stress is described as the imbalance between pro-oxidants (Reactive oxygen species) and antioxidants levels commonly called redox imbalance. It occurs in a discrete step-wise process of initiation, propagation, and termination stages via the generation of free radicals. These steps bring about effects that have contributed to hypertension through endothelial dysfunction, reduced bioavailability of Nitric oxide, atherosclerotic plaque formation, and reduction of toxic oxidants. Hence, oxidative stress mechanism is implicated in hypertension and thus, the daily intake of antioxidants-containing foods and products to supplement depleted endogenous antioxidants is recommended.
The document discusses oxidative stress and reactive oxygen species (ROS). It defines ROS and lists some examples like superoxide anion radical, hydroxyl radical, and hydrogen peroxide. It describes how ROS are produced endogenously through processes like mitochondrial electron transport, and exogenously through factors like pollution, radiation, and xenobiotics. The effects of ROS include DNA damage and modulation of signal transduction pathways. It also discusses antioxidants, dividing them into antioxidant enzymes like superoxide dismutase and catalase, chain breaking antioxidants like vitamins C and E, and transition metal binding proteins.
Free radicals are unstable molecules that can damage cells. This document discusses free radicals, how they are produced in the body, and how they damage lipids, proteins, and DNA through oxidation. It also describes biomarkers that are used to measure free radical damage, such as markers of lipid peroxidation (MDA, HNE), protein oxidation (protein carbonyls), and DNA oxidation (8-OHdG). Antioxidants in the body help neutralize free radicals and prevent oxidative damage.
Nitric oxide (NO) is a gas that acts as a signaling molecule in various physiological processes. It is produced by nitric oxide synthase enzymes from arginine and oxygen. NO signals the dilation of blood vessels by diffusing into endothelial cells and increasing cGMP levels, which leads to smooth muscle relaxation. It also prevents platelet aggregation, acts as a neurotransmitter, and is involved in the immune response by assisting macrophages in killing bacteria. While NO is important for many functions, too much or too little production can be harmful and lead to conditions like hypertension or infection.
nitrogen is the most abundant atmospheric gas,yet is a limiting factor. this presentation is a bird's eye view, of nitrogen cycle, its fixation, uptake and assimilation in plants
Nitric oxide synthases (NOS) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. There are three main types of NOS - neuronal NOS, inducible NOS, and endothelial NOS - located in different tissues and performing different functions. NOS is a heme-containing dimerized protein that uses NADPH, FAD, FMN, tetrahydrobiopterin, and heme as cofactors. It converts L-arginine to citrulline and NO via a two-domain mechanism involving electron transfer from the reductase domain to the oxygenase domain. Due to its importance in various physiological processes, NOS and NO signaling have been
This document describes a study that compared the antioxidative and anti-inflammatory effects of Taraxacum officinale (common dandelion) methanol extract (TOME) and water extract (TOWE) in lipopolysaccharide-stimulated RAW 264.7 cells. The extracts reduced nitric oxide production and restored depleted glutathione levels and antioxidant enzyme activities. Both extracts also inhibited lipopolysaccharide-induced inducible nitric oxide synthase gene expression and nuclear factor-κB activation. TOME showed more potent effects than TOWE, which was attributed to its higher phenol, luteolin, and chicoric acid content. The results suggest the extracts inhibit oxidative stress and inflammation by elevating antioxidant enzymes and suppressing
This document summarizes reactive oxygen species (ROS) and their role in periodontal disease. It begins by defining antioxidants, free radicals, and oxidative stress. It describes the various ROS like superoxide, hydroxyl radical, nitric oxide, and peroxynitrite. It outlines the sources of free radicals including internal sources like mitochondria and external sources like smoking. It details the effects of ROS on lipids, proteins, DNA and tissues. This causes cellular injury and death. Evidence shows elevated ROS in periodontal disease tissues and its role in tissue damage by affecting gingival cells, bone, ground substance, and collagen. The document also discusses antioxidant defense systems in the body like vitamins C and E, carotenoids,
Nitric oxide (NO) is produced in the body by nitric oxide synthase (NOS) enzymes from the amino acid L-arginine. NO acts as both an intracellular and extracellular signaling molecule and is involved in many physiological processes like neurotransmission and smooth muscle relaxation. There are three isoforms of NOS - neuronal NOS, inducible NOS, and endothelial NOS. NO stimulates soluble guanylate cyclase which increases cyclic GMP levels and triggers smooth muscle relaxation. In addition to cGMP signaling, NO can also signal through S-nitrosylation of proteins or by forming nitrite and nitrate storage pools.
Nitric oxide is formed in the body from L-arginine and can have both protective and tumor-promoting effects. It reacts with superoxide to form peroxynitrite, a reactive molecule that can damage biomolecules. Excess nitric oxide production can be inhibited by nitric oxide synthase inhibitors. Nitric oxide has direct effects through reactions with metals and inhibition of mitochondrial respiration, and indirect effects through peroxynitrite formation leading to oxidative stress.
Presentation on genetics of nitrogen fixation by Tahura MariyamTahura Mariyam Ansari
this presentation is about what is the genetics involvement in nitrogen fixation i.e which gene is responsible etc....
the contents include Genetics of N2 fixing microorganisms, Bacterial Nodulation Genes and Regulation of nod Gene Expression, Nif Genes and their Regulation in K. Pneumoniae & Cyanobacteria, Nitrogen fixation mechanism
Nitrogenase Types, Structure and Function, Alternative nitrogenase, Substrate for Nitrogenase, Electron proteins and Hydrogen evolution
The document discusses DNA damage induced by dipyrone (NaDip) in the presence of transition metal ions. It aims to demonstrate DNA damage caused by NaDip and metal ions in vitro. The methods used include recombinant DNA techniques using the pUC19 cloning vector, plasmid DNA extraction, and nucleic acid electrophoresis to measure DNA damage. The results show that NaDip combined with copper, iron, or nickel ions damaged plasmid DNA, forming smears on gels. The discussion notes that previous studies found these metal ions can interact with and damage DNA through free radicals. The conclusions state that more study of NaDip's effects is needed but it may damage DNA through free radicals generated with metals, and other drugs could act similarly.
This document discusses the endothelium and nitric oxide (NO). It begins by defining the endothelium as the thin layer of cells lining blood vessels. Endothelial cells release substances that modulate vessel tone by causing contraction or relaxation. Studies in the 1980s identified endothelium-derived relaxing factor (EDRF), which was later determined to be NO. NO is synthesized from L-arginine by nitric oxide synthase (NOS). There are three main types of NOS - neuronal (nNOS), inducible (iNOS), and endothelial (eNOS). NO signals smooth muscle relaxation through a cGMP pathway. NO has many roles in the nervous, circulatory, immune, and other body systems. The mechanisms and functions of NO are
Isoprostanes (IsoPs) are important molecules since they provide an accurate measure of oxidative stress.
It has been verified that the levels of IsoPs are increased in several human diseases. Therefore, they have been widely used in research to explore the role of oxidative stress in the pathogenesis of disease and their measurement can impact positively on clinical medicine.
INSTITUT KURZ is specialized in the measurement of isoprostanes.
Visit our website: https://www.institut-kurz.com/
The endothelium is the thin layer of cells that lines the interior surface of blood vessels. Endothelial cells release nitric oxide (NO), which acts as a vasodilator and modulates vessel tone. NO is synthesized from L-arginine by the enzyme nitric oxide synthase. It binds to guanylate cyclase, increasing cGMP levels and causing smooth muscle relaxation through various mechanisms. NO has many roles in the nervous, circulatory, immune and other body systems. It is involved in processes like vasodilation, neurotransmission, and host defense. NO synthesis can be inhibited by L-arginine analogs, while NO donors are used therapeutically to elicit smooth muscle relaxation.
Oxidative stress is the main metabolic process that causes mitochondrial dysfunction. In this presentation we show different oxidative stress pathways and the main solutions to prevent mitochondrial damage by using non enzymatic antioxidants and boosting antioxidant enzymatic systems.
This document summarizes a study that investigated the effects of melatonin on inflammatory responses induced by Prevotella intermedia lipopolysaccharide (LPS) in murine macrophages. The study found that melatonin suppressed the LPS-induced production of nitric oxide and interleukin-6 by inhibiting the NF-κB and STAT1 signaling pathways. Melatonin blocked NF-κB signaling by inhibiting the nuclear translocation and DNA-binding activity of the NF-κB p50 subunit. This suggests that melatonin may help reduce host inflammatory responses associated with periodontal disease by modulating these signaling pathways and inflammatory mediators.
A brief description of all topics to recent advances,SDD, host modulation and diabetes, host modulation in smokers, chemically modified tetracyclines, bisphosphonates
This document discusses nitric oxide homeostasis and its role in neurodegenerative diseases such as Alzheimer's and Parkinson's. It begins by introducing nitric oxide biosynthesis by nitric oxide synthases and how their expression is altered in Alzheimer's. It then discusses factors that control nitric oxide levels, including endogenous inhibitors, tetrahydrobiopterin levels, and nitric oxide reactivity with superoxide to form peroxynitrite. Overall, the document analyzes how imbalances in nitric oxide signaling can contribute to neurodegeneration through oxidative stress and damage.
Nitric oxide and its role in reproductiondavid sonwani
Nitirc oxide an noble gas signaling molecule present in all types of living organism as an excretory product. has multiple role in body including defense cure and mainly reproduction.
This document discusses reactive oxygen species, reactive nitrogen species, and redox signaling. It covers the following key points:
- Nitric oxide is an important signaling molecule produced through the oxidation of L-arginine by nitric oxide synthase. There are three NOS isoforms.
- Reactive oxygen species include superoxide and hydrogen peroxide. Superoxide is produced by NADPH oxidase and can be converted to hydrogen peroxide. These molecules are involved in cell signaling but can also cause damage.
- Hydrogen sulfide is another gasotransmitter that regulates various physiological processes through protein persulfidation.
- Reactive species can modify protein cysteine residues through oxidation
The document examines how long-term low-dose exposure of human urothelial cells to sodium arsenite activates the lipocalin-2 (LCN2) gene via promoter hypomethylation. It finds that the LCN2 promoter in arsenic-exposed cells is hypomethylated compared to unexposed cells, leading to increased LCN2 expression. This overexpression of LCN2 enhances cellular transformation, anti-apoptotic activity, and inflammatory responses in the arsenic-exposed cells through mechanisms involving NF-κB and increased iron and reactive oxygen species levels.
The imbalance between free radical production and endogenous antioxidant defence may result in cellular oxidative stress, causing oxidative damage to various cellular components, such as DNA, proteins and membrane lipids. The human system employs the use of endogenous enzymatic and non-enzymatic antioxidant defence systems against the onslaught of free radicals and oxidative stress.
Unsurprisingly, oxidative damage has been implicated in and is believed to be a key factor causing various pathological conditions, such as cardiovascular disease, neurodegenerative disease, diabetes and cancer. Free radicals can be quenched through a number of mechanisms. Antioxidants directly scavenge free radicals (e.g., via hydrogen atom transfer or electron transfer), prevent free radical formation by chelating metal ions and by interrupting the radical chain reactions of lipid peroxidation, thus retarding its progression. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Non-enzymatic antioxidants include vitamins A, C, and E, glutathione, alpha-lipoic acid, carotenoids, and coenzyme Q10. Other antioxidants include polyphenols, minerals (copper, zinc, manganese, and selenium), and cofactors (B-vitamins). Together, antioxidants work synergistically with each other using different mechanisms against different free radicals and stages of oxidative stress.
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1. PRESENTED BY:
SONAL GOYAL
2ND YR POSTGRADUATE
DEPARTMENT OF PERIODONTOLOGY
Inducible Nitric Oxide
Synthase (iNOS) In Chronic
Periodontitis
GUIDED BY:
DR. MANORANJAN
DR. RACHANA
3. Introduction
• The pathogenesis of periodontitis consists of a cascade of inflammatory
and immunological reactions, which have not yet been fully elucidated.
• Recently, NO has been shown to be a vital molecule in inflammatory
processes.
• Since its discovery as a biologically active molecule in the late 1980’s,
nitric oxide (NO) has been found to play an important role as signal
molecule in many parts of the organism as well as cytotoxic or
regulatory effector molecule of the innate immune response.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
4. Nitric oxide
• Nitric oxide, also known as nitrogen monoxide
• Highly reactive radical produced from the amino acid arginine by the
enzyme nitric oxide synthase (NOS).
• Implicated in a wide variety of regulatory mechanisms ranging from
vasodilatation and blood pressure control to neurotransmission.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
5. Synthesis of nitric oxide
• NO is formed by the :
Oxidative deamination of the amino acid l-arginine
Conversion of l-arginine to l-citrulline plus nitric oxide.
Catalysed by nitric oxide synthases.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
6. The second step is a three electron oxidation, again requiring
molecular oxygen and NADPH to perform an electron removal,
oxygen insertion, and carbon-nitrogen bond scission to form L-
citrulline and the free radical nitric oxide.
Two primary steps have been identified. The first step, a two
electron oxidation, is a hydroxylation of one of the guanidino
nitrogens of L-arginine requiring molecular oxygen and
nicotinamide adenine diphosphate (NADPH) to form NG-hydroxy-
Larginine.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
7. • Thus the five electron oxidation of the terminal guanido nitrogen
of the amino acid l -arginine to form NO plus l-citrulline, in a
complex reaction involving....
• Molecular oxygen
• NADPH
• Enzyme bound heme, FAD, FMN
• Reduced thiols, and tetrahydrobiopterin.
cosubstrates
Redox factors
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
8. • For all three NOS isoforms, NO synthesis depends upon the :
• [Ca2+ i = resting intracellular] are required for their binding
calmodulin and, consequently, for their becoming fully activated.
• For eNOS and bNOS, increase in resting intracellular [Ca2+ i]
concentrations required.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
9. • By contrast, iNOS appears able to bind calmodulin with extremely
high affinity even at the low [Ca2+ i] characteristic of resting cells.
• Hence, the activity of iNOS in immunoactivated cells is no longer
temporally regulated by intracellular calcium transients.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
10. Since NO may be either stabilized or degraded through its
interactions with diverse intracellular or extracellular chemical
moieties, the localization of NOS within the cell might be
expected to influence the biological role and chemical fate of the
NO produced by the enzyme.
Almost every conceivable intracellular organelle has been
postulated as a possible site for NO synthesis, from the plasma
membrane to the cell nucleus.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
11. NITRIC OXIDE SYNTHASES
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
Isoforms of
NOS
Constitutively
produced
(cnos)
Neuronal
Endothelial
Maintains
normal
physiology
Inducible (inos)
Involved
principally in
inflammatory
processes.
12.
13. Human genes for the NOS isoforms are officially categorized in the order of
their isolation and characterization; thus, the human genes encoding nNOS,
iNOS, and eNOS are termed NOS1, NOS2 , and NOS3 , respectively.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
15. • Absent in resting cells, but the gene is rapidly expressed in
response to stimuli such as proinflammatory cytokines.
• Once present, iNOS synthesize 100–1000 times more NO than the
constitutive enzymes and does so for prolonged periods.
•This high concentration of NO may inhibit a large variety of
microbes, but may also potentially damage the host, thereby
contributing to pathology.
Inducible nitric oxide synthases
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
16. • Induced in macrophages.
• Major cytotoxicity.
• Because of its affinity to protein-bound iron, NO can inhibit a
number of key enzymes that contain iron in their catalytic centres.
• Down-regulates Th1 cytokine responses.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
17. • It seems reasonable to assume that the increased levels of NO are
produced by iNOS expressing cells during inflammation of the
periodontal tissue.
• This is analogous to other phlogistic molecules produced during the
inflammatory process, such as prostaglandin E2, IL-1β and TNF-α.
• The presence of iNOS and conceivably NO release at the
inflammatory sites may have a role in selecting the type of T-cell
response.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
18. • Proinflammatory cytokines (e.g. IL-1β) and Th1 cytokines (e.g. IL-2
& IFN-γ) have been shown to have a stimulatory effect on iNOS
expression,
• Whereas Th2 cytokines (e.g. IL-4) have been shown to have an
inhibitory effect in vivo,
• Thus indicating an important reciprocal role of Th1 and Th2 T-cell
subsets in iNOS synthesis.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
19. • The presence of iNOS expressing macrophages in an environment
rich in Th2 cytokines is not altogether surprising because iNOS
expression by IFN-γ and/ or TNF-γ primed macrophages is
augmented by IL-10 stimulation.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
22. • Increased NO production is seen with macrophage stimulation by
Porphyromonas gingivalis LPS, Actinobacillus
actinomycetemcomitans, P. intermedia, P. nigrescens, and F.
nucleatum.
• Conflicting results regarding its role in periodontitis exists:
An increase in local production of nitric oxide via iNOS can be
seen in periodontal diseases, however,
Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and severity of human
periodontal disease. Oral diseases 2002;8:254-260.
23. The presence of NO is
increased in alveolar
bone resorption
This molecule may have
an effect on the growth
and survival of the
bacteria implicated in
periodontal disease
May function as a
mediator for the control
of clastic activity and
avoiding excessive bone
resorption
24. Inducible production of NO in periodontitis
Increased number of iNOS immunoreactive
inflammatory cells in tunica propria and in
immunoreactivity of basal layer and the uppermost
layer of epithelial lining of the gingiva.
Induce iNOS production
Gingivomucosal immune and epithelial cells
Toxins, enzymes, metabolites of gram negative
bacteria
Lohinai ZM, Szabo C. Role of nitric oxide in physiology and patophysiology of periodontal
tissues. Med sci monit 1998;4:1089-1095.
25. Pro-inflammatory cytokines produced by
inflammatory cells
Trigger resident and/or immigrant cell
population
iNOS
Non-specific immunity.
Acts as cytotoxic and cytostatic agents.
Lohinai ZM, Szabo C. Role of nitric oxide in physiology and patophysiology of periodontal
tissues. Med sci monit 1998;4:1089-1095.
26. Immunoregulation + low concentration of cellular l-arginine
iNOS (in macrophages)
NO Superoxide
Forms toxic oxidant peroxynitrite
Lohinai ZM, Szabo C. Role of nitric oxide in physiology and patophysiology of periodontal
tissues. Med sci monit 1998;4:1089-1095.
27. Killing or stasis of microorganism
Bacterial wall produce more NO
Positive feedback cycle
Wall component of gram negative bacteria killed by NO
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
28. DNA injury
Tissue breakdown via
Oxidation reaction Nitration reaction
Inhibition of
energy generating
enzyme
Activation of
proinflammatory
enzyme
Cytotoxicity towards the host tissue
Excessive NO production
Cyclooxygenase
+
MMP
Periodontal
tissue damage
29. • In periodontitis, stimulatory and inhibitory actions of nitric oxide
have been found, according to differences in concentration level.
• It is difficult to predict whether increased production of NO during
inflammation is likely to increase bone loss or prevent it.
Role Of iNOS In Bone Destruction
Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and severity of human
periodontal disease. Oral diseases 2002;8:254-260.
30. • Batista et al and Kroncke et al concluded that:
• Since, PMNs is the major source of NO and taking into account
that these cells do not present an innermost contact with bone, NO
originating from PMNs may be related to beneficial effects rather
than bone loss in periodontal disease.
31. The presence of constitutive and
inducible forms of NOS have been
demonstrated in both osteoblasts and
osteoclasts.
Osteoblasts have been shown to
produce a low basal level of NO
which is important for normal
function.
Significant increases or decreases in
NO production via inflammatory
stimuli or NOS inhibitors have been
found to inhibit osteoblast
proliferation and differentiation, and
in some cases, result in apoptosis.
32. • Low NO levels also appear to be important for the normal function
of osteoclasts.
• If NO production is abolished or significantly increased, then bone
resorption ceases under normal conditions.
• However, NO produced by iNOS also serves as an autocrine
negative feedback signal that regulates osteoclastogenesis.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
33. High NO levels appear to
antagonize the effects of PGE2 on
bone resorption, whereas low
levels appear to act in synergy in
enhancing bone resorption.
Therefore, in the presence of
inflammatory or pro-osteoclastic
mediators, the inhibition of iNOS may
result in significantly increased bone
resorption.
Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen and nitrogen species, gene
induction and mitochondrial function. Mol Aspects Med 2002;23:209-285.
34. Beneficial effects Detrimental effects
•Antimicrobial activity
•Immune modulation
•Inhibition of microvascular
thrombosis
•Increased tissue perfusion
•Cytotoxic action towards host tissue
including alveolar bone
•Gingival redness- due to vasodilatory
effect of NO
•Gingival swelling – vascular
permeability
•Increasing effect of NO
•BOP due to inhibitory effect of NO
on platelet aggregation and adhesion
• Increased alveolar resorption – due
to stimulatory effect of NO on the
activity of the osteoclasts.
35. • NO and other free radicals participate in the activation of
neutrophil pro-collagenase and they also suppress proteoglycan
and collagen synthesis.
• This may be one of the mechanisms by which NO contributes to
the profound early loss of collagen in gingival lesions.
• The induction of iNOS expression may also inhibit fibroblast
proliferation and induce apoptosis, contributing to the imbalance
of tissue destruction with tissue repair that is characteristic of
periodontitis.
Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and severity of human
periodontal disease. Oral diseases 2002;8:254-260.
36. Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and severity of human
periodontal disease. Oral diseases 2002;8:254-260.
NO may also activate the recruitment of
phagocytes and,
Conversely, modulate the degree of
inflammation,
Inducing a strong and specific inhibition
of T cell proliferation in both Th subsets.
37. • As B cells and plasma cells appear to play a more important role in
the progressive lesion of chronic inflammation in periodontal
disease than T cells,
• It is possible that NO plays a role in the progression of periodontal
disease through the suppression of the T- cell immune response.
Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and severity of human
periodontal disease. Oral diseases 2002;8:254-260.
38. The lack of significant differences in the number of iNOS+ cells
between gingivitis and periodontitis may suggest that it is a
normal part of the inflammatory process, and the larger number
of cells in gingivitis would indicate that it is not related to tissue
destruction or bone loss.
Nevertheless, taking into account that NO production is
kept remarkably elevated throughout the continuing
increase in disease severity, the killer properties of NO may
not be related to the concentration of NO generated per
enzyme, but rather to the duration of NO produced.
Number or duration??
Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and severity of human
periodontal disease. Oral diseases 2002;8:254-260.
39.
40.
41.
42. • Akopov and Kankanian
Activated PMN
Inhibits NO- induced
stimulation of cGMP
accumulation in cultured
fibroblasts
More in periodontitis
patients than in healthy
Deactivation of NO by
activated PMNs maybe one
of the pathophysiological
mechanism of periodontitis.
Release superoxide
NO
peroxynitrite
Prevents activation
of guanylate cyclase
43. Relationship between ROS and RNS
During acute
inflammation, the NO
generated by NOS is a
mediator of the non
specific defense, the NO,
together with ROS,
having a cytotoxic and
cytostatic effect on the
bacterial agents.
In the inflammatory cells
it is stimulated the
generation of NO and of
superoxide anion (O2•–).
NO reacts with O2•– and
other ROS, leading to
the generation of RNS.
Camelia A, Alb S, Suciu S, et al. Oxygen and nitrogen reactive species implications in the
etiopathogenesis of the periodontal disease. Bulletin USAMV-CN 2007;64:1-5.
44.
45. Paradoxically, ROS and
RNS take part in the
regulation of some
physiological processes,
but, on the same time,
they destroy non-self and
self cells.
The impact of their
chronic synthesis on the
periodontium has
consequences unrelated
with their synthesis rate
and with the composition
of the environment in
which this process takes
place
Camelia A, Alb S, Suciu S, et al. Oxygen and nitrogen reactive species implications in the
etiopathogenesis of the periodontal disease. Bulletin USAMV-CN 2007;64:1-5.
46. Healthy periodontium
Superoxide dismutase
Decreased catalyzes dismutation of superoxide
Prevents the formation of peroxynitrite
Anti-oxidant ascorbic acid
Scavenger of reactive nitrogen species.
Lohinai ZM, Szabo C. Role of nitric oxide in physiology and patophysiology of periodontal
tissues. Med sci monit 1998;4:1089-1095.
47. Clinical implications
• Selective iNOS inhibition-
1. Mercaptoethylguanidine (MEG):
Selective inhibitor
Scavenger of peroxynitrite
Significantly reduces the plasma extravasation in gingivomucosal
tissue
Decreased degree of alveolar bone destruction.
Lohinai ZM, Szabo C. Role of nitric oxide in physiology and patophysiology of periodontal
tissues. Med sci monit 1998;4:1089-1095.
48. 2. Glucocorticoids:
iNOS inhibiting ability.
3. Tetracyclines
Used in treatment of juvenile periodontitis
Eliminates bacteria
Prevent bone loss
Inhibits peroxynitrite- dependent oxidative process.
Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide synthase expression in
periodontitis. J Periodont Res 2000; 35: 369-373.
50. Studies
Author Study Conclusion
Lappin et al,
2000
Examined the localisation of
iNOS in biopsies from
patients with periodontitis.
The periodontitis diseased tissue
demonstrated a greater level of iNOS
expression than the healthy tissue.
The source of iNOS in the periodontal
tissues was determined to be the
macrophage, with the endothelial cells
also contributing.
A role for NO in the inflammatory
response of periodontal tissues is
suggested, but the precise role was not
elucidated.
51. Authors Study Conclusion
Kendall et al,
2001
Described the role of nitric
oxide in periodontal tissue
destruction.
iNOS, identified in several cell
types such as macrophages and
polymorphonuclear cells, is
expressed in response to
inflammatory stimuli, such as IL-1,
TNF-a, IFN-c and LPS, preferably
in a synergic manner, yielding high
amounts of NO for a long time
period.
Michiko et al,
2001
Expression of cytokine and
inducible nitric oxide
synthase in inflamed
gingival tissue.
iNOS expression in gingiva with
periodontitis was significantly
higher than that in the healthy
gingiva. NO production by
macrophages and PMNL via iNOS
was enhanced in periodontal
lesions and resulted in the
progression of periodontitis.
52. Authors Study Conclusion
Camelia et al,
2007
Oxygen and nitrogen
reactive species
implications in the
etiopathogenesis of the
periodontal disease
Found a statistic significant
increase of the nitric oxide in
mixed saliva of patients with
periodontal disease, which is the
expression of the involvement of
the nitro-oxidative stress.
Batista et al,
2002
To identify and quantify the
expression of iNOS in
samples of plaque induced
gingivitis and localized
chronic periodontitis, to
suggest the possible
relationship between this
molecule and bone
resorption activation and
tissue destruction during the
progression of periodontal
disease.
iNOS increases in the presence of
periodontal disease. Also,
polymorphonuclear cells present
an additional activation pathway
in periodontal disease, expressing
significant iNOS and probably
representing an important source
of NO in human periodontal
disease.
53. Conclusion
Low concentrations of basally produced NO maintain normal
homeostasis, and are protective under physiological conditions
in circumdental tissues.
However, NO may be detrimental when produced in excess
in inflammation, may destroy the host tissues as well not
only the invading microorganisms.
Hence, selective inhibition of the inducible isoform of
nitric oxide synthase and maintenance of constitutive NO
production may be of therapeutic utility in periodontitis.
54. Reference
1. Lappin DF, Kjeldsen M, Sander L, Kinane DF: Inducible nitric oxide
synthase expression in periodontitis. J Periodont Res 2000; 35: 369-
373.
2. Lohinai ZM, Szabo C. Role of nitric oxide in physiology and
patophysiology of periodontal tissues. Med Sci Monit 1998;4:1089-
1095.
3. Batista AC, Silva TA, Chun JH, Lara VS. Nitric oxide synthesis and
severity of human periodontal disease. Oral diseases 2002;8:254-
260.
55. 4. Camelia A, Alb S, Suciu S, et al. Oxygen and nitrogen reactive species
implications in the etiopathogenesis of the periodontal disease. Bulletin
USAMV-CN 2007;64:1-5.
5. Jackson MJ, Papa S, Bolanos J, et al. Antioxidants, reactive oxygen
and nitrogen species, gene induction and mitochondrial function. Mol
Aspects Med 2002;23:209-285.
6. Hirose M, Ishihara K, Saito A, et al. expression of cytokines and
inducible nitric oxide synthase in inflamed gingival tissue. J
Periodontol 2001;72:590-597.
Editor's Notes
NO synthesis depends upon the enzyme’s binding to the ubiquitous calcium regulatory protein calmodulin.
Proposed scheme of cytotoxic pathways involving nitric oxide (NO¥) and peroxynitrite (ONOOÐ) in periodontitis. Proinflammatory mediators induce the expression of the inducible NO synthase (iNOS). NO, in turn, combines with superoxide to yield peroxynitrite. Under conditions of low cellular L-arginine NOS may produce both superoxide (*) and NO, which then can combine to form peroxynitrite. NO and peroxynitrite (alone or in combination or synergy) triggers a variety of cytotoxic processes, such as inhibition of mitochondrial respiration, tyrosine nitration, anti-oxidant depletion, etc. Activation of the inducible cyclooxygenase (COX-2) by NO or peroxynitrite may also amplify the inflammatory response. A distinct pathway of inflammation involves the development of DNA single strand breakage, with consequent activation of the nuclear enzyme poly ADP-ribose synthetase (PARS). Depletion of the cellular NAD+ leads to inhibition of cellular ATP-generating pathways leading to cellular dysfunction.
Although the production of NO or peroxynitrtie via inos serves to induce killing or stasis of the invading mcroorg, the excessive production of these species may lead to
Sparse inos cells in clinically healthy gingiva tissues
Inos within the blood vessel lumen
a. Inos Pmn with intense staining in the plaque induced gingivitis both inside lumen of bv and outsid
b. Close up