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.
1. A SEMINAR ON
OXIDATIVE STRESS MECHANISM IN HYPERTENTION
BY
MLS. ODUMOSON NEWTON CLESTON(Intern)
TO
THE DEPARTMENT OF CHEMICAL PATHOLOGY, MEDICAL
LABORATORY SERVICES,
FEDERAL MEDICAL CENTRE, YENAGOA
IN PARTIAL FULFILLMENT FOR THE REQUIREMENTS FOR THE
ADMISSION AS AN ASSOCIATE MEMBER OF MEDICAL
LABORATORY SCIENCE COUNCIL OF NIGERIA (AMLSCN)
SUPERVISOR: MLS. OFOR IGRI
JULY, 2016
2. OUTLINE
INTRODUCTION
HYPERTENTION
SOME CAUSES OF HYPERTENSION
OXIDATIVE STRESS
PATHOPHYSIOLOGY OF OXIDATIVE STRESS
(MECHANISM OF OXIDATIVE STRESS)
EFFEECTS OF OXIDATIVE STRESS
BIOMARKERS OF OXIDATIVE STRESS
CONCLUSION
RECOMMENDATION
3. INTRODUCTION
In recent times, there has been an increase need in
finding out some possible causes of hypertension.
Hence the growing interest of oxidative stress
mechanism in hypertension.
5. Some Causes of Hypertension (redox imbalance)
Damage
(Pro-oxidants)
Defense
(Antioxidants)
Oxidant-Antioxidant Balance
Decrease of antioxidant defense system
Oxidative damage
(Roberts et al., 2002)
6. OXIDATIVE STRESS
Imbalance between reactive oxygen species (ROS)
and antioxidants.
Under normal conditions, cells are able to balance
the production of oxidants and antioxidants.
Oxidative stress occurs when cells are subjected to
excess levels of ROS or as a result of antioxidant
depletion.
(Koo et al., 2004)
8. PATHOPHYSIOLOGY OF OXIDATIVE STRESS
(MECHANISM OF OXIDATIVE STRESS)
Mechanism of oxidative stress is a complex
pathway and their effects depends on the target
sites. Either cells, tissues, lipids, nucleic acids,
proteins and enzymes.
All pathways leading to oxidative stress are cause
by a family of highly reactive molecules called
Reactive Oxygen Species(ROS). These reactive
oxygen species includes Hydroxyl radical,
superoxide anion radical, hydrogen peroxide,
singlet oxygen, nitric oxide radical and various
lipid peroxides.
(Vaziri et al., 2006)
9. The mechanism of oxidative stress starts by
formation of free radicals that initiate
chemical chain reactions to occur.
It involves three step-wise process
Initiation: free radicals abstracts electrons
and/or hydrogen atoms from healthy target
cells.
Propagation: Abstracted electron is been
oxidized in the target site to form ROS and
these chain of reactions continues on and on.
Termination: Finally terminated by the
addition of an antioxidant.
(Vaziri, 2002)
10. EFFECT OF OXIDATIVE STRESS MECHANISM
Cellular damage (cell death).
Tissue injury (necrosis).
DNA damage (mutation).
Lipid peroxidation in unsaturated fatty acids,
membranes and foods.
Protein denaturation and
Enzyme inhibition
(Nava et al., 2003)
11. EFFECTS OF OXIDATIVE STRESS
MECHANISM IN HYPERTENSION
Endothelial dysfunction
Arthrosclerosis plaque formation
Reduce bioavailability of NO
Production of toxic oxidants (pero-oxynitrite)
(Norsratola, 2008)
12. BIOMARKERS OF OXIDATIVE STRESS
I. BIOMARKERS OF LIPID PEROXIDATION:
MDA level modified proteins in atherosclerosis
HNE level permanently formed at physiological conditions but in larger quantities in
neurodegenerative, atherosclerotic and inflammatory lesions
Acrolein present in various environmental sources (cigarette smoke) but is increased in
cardiovascular diseases
Isoprostanes family of prostaglandins generated by free radicals catalyzed peroxidation of esterified
arachidonic acid
II. BIOMARKERS OF PROTEIN OXIDATION (major targets for reactive oxygen species):
Carbonylated proteins level Lys, Arg, Pro and Hys are the principle aminoacid residues to form
carbonyl derivates
3-nitrotyrosine (NO2-Tyr)
Biomarkers derived from Tyr 3-chlorotyrosine (Cl-Tyr)
3-bromotyrosine(Br-Tyr)
III. BIOMARKERS OF OXIDATIVE DAMAGE TO DNA 8-hydroxyl-2`-deoxyguanosine
8-oxo-7,8-dihydro-2`-deoxyguanosine
8-hydroxyguanine
IV. OTHER BIOMARKERS
Glutathion level
(Ding et al., 2008)
13. CONCLUSION
A paradox in metabolism is that while the vast majority
of complex life on earth requires oxygen for its existence,
oxygen is a highly reactive molecules that damages living
organism by producing reactive oxygen species (ROS)
leading to oxidative stress which is implicated in
hypertension.
However the body's protection system i.e. the general
antioxidants system prevents these reactive species from
being formed or remove them before they can damage
vital components of cells and tissues.
Thus oxidative stress mechanism is implicated in
hypertension.
14. RECOMMENDATIONS
It is therefore imperative to recommend the daily
intake of antioxidants either from diet, fruits,
vegetables to supplement the endogenous
antioxidants.
similarly, the risk factors of oxidative stress
generation either from endogenous or exogenous
sources should be avoided, these could help reduce
prevalence's of hypertension as a result of oxidative
stress mechanisms.