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Michael AB Naafs*	
Dutch Internist Endocrinologist, Netherlands
*Corresponding author: Michael AB Naafs, Dutch Internist Endocrinologist, Netherlands
Submission: January 23, 2019; Published: January 28, 2019
Copper Nanoparticles and Antioxidant
Stress: Problem Makers or Solvers?
Introduction
The increased use of metal nanoparticles in the food chain is an
increasing concern. Nanoparticles (NPs) are used in various areas,
including medicine, electronics, cosmetics, oil lubricants and also
in the food chain. The extensive use of these NPs allows them to
be released into the environment either during production use or
disposal. Phytotoxicity of copper NPs has already been reported
[1]. Copper NPs are believed to cause oxidative stress by increasing
the activity of oxidative stress enzymes as catalase, superoxide
dismutase and glutathion-S-transferase [1,2]. Copper NPs cause
in this way a dose dependent toxicity via inducing reactive oxygen
species (ROS) and nitrous oxide (NO) [3]. Toxicity of copper NPs
has been studied mainly in animals and is manifested as hepato-
and renal toxicity, splenic toxicity, neurotoxicity ,gene toxicity
and carcinogenicity at LD 50 values of nano- copper (23.5nm) of
413mg/kg/body/weight [4]. Copper (Cu) is a redox active metal
and an essential nutrient in all species. Deficits and excessive
amounts can result in human disease and oxidative stress plays a
major role in both circumstances. Copper deficiency can contribute
to the development and progression of cardiovascular disease and
diabetes [5]. Copper NPs showed antidiabetic and antioxidant
properties [6]. In addition, copper NPs are used as antibacterial
and antifungal agents [7]. So, are copper NPs problem makers or
problem solvers? In this mini-review the various aspects of copper
NPs will be discussed.
Synthesis
Copper NPs are very attractive due to their high thermal
conductivity and relatively low costs compared to e.g. gold and
silver nanoparticles. They can be synthesized by physical, chemical
and green techniques. Vacuum vapor deposition, pulsed laser
ablation, pulsed wire discharge and mechanical wiring are physical
techniques Chemical reduction ,microemulsion techniques,
sonochemical reduction, electrochemical, microwave assisted and
hydrothermal are chemical approaches for the synthesis of copper
nanoparticles [4,5,8]. Green synthesis of copper NPs is using
different plants, bacteria and fungi [9,10].
Characteristics
The properties of copper NPs depend largely on size, structure,
shape ,surface properties, particle aggregation, agglomeration and
optical characteristics. Their catalytic activity increases with the
decrease in size of copper NPs [11].
Catalytic activity
Catalysts are substances that promote and accelerate chemical
reactions without being consumed. Catalysis based on copper
NPs may benefit for example the synthesis of methanol or the
production of hydrogen on an industrial scale [11-13].
Antibacterial/Antifungal action
It has been known for a long time that copper and copper
alloys have antimicrobial properties [14]. Copper has two key
properties that are exploited in consumer products and medical
devices. Copper has potent biocidal properties and is critical for
most tissues including the skin. In the skin, copper is involved in the
synthesis and stabilization of extracellular matrix skin proteins and
angiogenesis [14]. It is therefore not surprising these properties
are leveraged of copper-oxide NPs impregnated wound dressings
[14-17].
Copper has antimicrobial activities against Gram-positive
and Gram-negative bacteria, including methicillin-resistant
Staphylococcus aureus (MRSA), Clostridium difficile, vancomycin-
Mini Review
Novel Techniques in
Nutrition and Food Science
C CRIMSON PUBLISHERS
Wings to the Research
243
Copyright © All rights are reserved by Michael AB Naafs.
Volume - 3 Issue - 2
Abstract
In this mini-review various aspects of copper nanoparticles are considered with a special emphasis on antioxidant stress. Copper nanoparticles
may become a problem maker for the environment but seems a problem solver in wound dressings and potentially in diabetes and cancer. Long-
term toxicity of copper nanoparticles is not known. An international registry agency should control the use of copper nanoparticles, especially in food
nanotechnology.
ISSN: 2640-9208
Nov Tech Nutri Food Sci Copyright © Michael AB Naafs
244
How to cite this article: Michael AB N.Copper Nanoparticles and Antioxidant Stress: Problem Makers or Solvers?. Nov Tech Nutri Food Sci. 3(2).
NTNF.000557. 2019. DOI: 10.31031/NTNF.2019.03.000557
Volume - 3 Issue - 2
resistant enterococci (VRE) and ESBL-producing species as well as
adenoviruses, Influenza A and fungi [14,18].
Cytotoxicity
Elevated copper levels result in the loss of membrane integrity,
which causes essential nutrients, including potassium and
glutamate to leak from cells and cause apoptosis [14]. Shafagh et
al. [19] studied cytotoxicity and apoptosis of copper oxide NPs on
a chronic myeloid leukemia (CML) K562 cell line. CuO NPs showed
selectivity towards the K562 cell line and are potentially a good
anti-cancer drug since it does not kill healthy cells. Apoptosis is
mediated through reactive oxygen species (ROS) production in
cancer cells, starting with P53 up-regulation [19]. Copper NPs also
induced apoptosis in a human skin melanoma cell line [20]. Similar
findings have been reported in a glial cancer cell line by Kukia et
al. [21].
Antioxidant activity
Copper oxide (CuO) NPs have higher toxic effects than Cu NPs
due to its oxidative property. CuO NPs stimulate photosynthesis at
low concentrations (<0.25mg/L) but suppression of photosynthesis
was observed at 1mg/L concentration. CuO NPs have been shown
to enhance the production of reactive oxygen species (ROS). At
low copper concentrations these ROS’ are protective in plants,
but at high Cu concentrations they may be cytotoxic and lead to
apoptosis, as mentioned before [4,22]. In addition, phytohormones
were also observed to be altered as a response to CuO NPs [23].
Most studies of the antioxidant effects of Cu NPs have been done
in animals [4]. The effect of antioxidant stress on cytochrome P450
and liver disease has been studied in rats and in cancer cell lines
[24,25]. In humans, curcumin Cu NPs have been studied mostly for
their potential anti-cancer activity [26,27]. Although curcumin has
been strongly advocated as a natural antioxidant in vitro, in vivo
and clinical studies are not able to provide evidence for a significant
role in the prevention of cancer. Even with modern curcumin nano-
formulations poor curcumin bioavailability could not be overcome
[28].
Metabolic disease
Nanotechnology has been used in diagnosing and monitoring
of diabetes by sensor technology [29,30]. Ghosh et al. [6] suggested
an antidiabetic effect of copper NPs by inhibiting the enzyme
alpha-glucosidase. Javed et al. [31] believe that copper NPs can
have hypoglycemic properties. Recently, it has been reported that
patients with metabolic syndrome need more vitamin C to break the
cycle of antioxidant depletion [32]. It is very well possible that the
antidiabetic effects of copper NPs are achieved by restoring vitamin
C mediated antioxidant depletion in the metabolic syndrome.
Therefore, it is interesting to know that CU NPs can be prepared
with ascorbic acid (vitamin C) by an aquous solution reduction
method [33]. It has also been known that vitamin C depletion
lowers the uptake of copper [34].
Conclusion
It is obvious that the widespread use of copper NPs in all
kind of sectors can lead to large environmental problems. The
use of these NPs has not been regulated and toxicity is not known
for the long term. Accumulation in the environment has clear
toxic effects on plants when these NPs are used in pesticides and
fertilizers. Detection of Cu NPs in the environment is extremely
difficult [35] and therefore copper NPs could be problem makers
in the long term. Long-term toxicity in humans is not known and an
international registry agency covering the use of NPs and Cu NPs
should be instituted therefore, especially for food nanotechnology
[28]. On the other hand, the use of Cu NPs in wound dressing and
diabetes sensor technology ,as well as their antimicrobial spectrum
are of proven benefit [14-18,30]. So, they are problem solvers, too.
The anti-cancer activity still has a potential future in nanomedicine
and has been explored not enough, yet. So, there has to be done
still much more research in the ecological effects of NPs, in
nanomedicine and especially in food nanotechnology..
References
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How to cite this article: Michael AB N.Copper Nanoparticles and Antioxidant Stress: Problem Makers or Solvers?. Nov Tech Nutri Food Sci. 3(2).
NTNF.000557. 2019. DOI: 10.31031/NTNF.2019.03.000557
Nov Tech Nutri Food Sci Copyright © Michael AB Naafs
Volume - 3 Issue - 2
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Copper Nanoparticles and Antioxidant Stress: Problem Makers or Solvers?_ Crimson Publishers

  • 1. Michael AB Naafs* Dutch Internist Endocrinologist, Netherlands *Corresponding author: Michael AB Naafs, Dutch Internist Endocrinologist, Netherlands Submission: January 23, 2019; Published: January 28, 2019 Copper Nanoparticles and Antioxidant Stress: Problem Makers or Solvers? Introduction The increased use of metal nanoparticles in the food chain is an increasing concern. Nanoparticles (NPs) are used in various areas, including medicine, electronics, cosmetics, oil lubricants and also in the food chain. The extensive use of these NPs allows them to be released into the environment either during production use or disposal. Phytotoxicity of copper NPs has already been reported [1]. Copper NPs are believed to cause oxidative stress by increasing the activity of oxidative stress enzymes as catalase, superoxide dismutase and glutathion-S-transferase [1,2]. Copper NPs cause in this way a dose dependent toxicity via inducing reactive oxygen species (ROS) and nitrous oxide (NO) [3]. Toxicity of copper NPs has been studied mainly in animals and is manifested as hepato- and renal toxicity, splenic toxicity, neurotoxicity ,gene toxicity and carcinogenicity at LD 50 values of nano- copper (23.5nm) of 413mg/kg/body/weight [4]. Copper (Cu) is a redox active metal and an essential nutrient in all species. Deficits and excessive amounts can result in human disease and oxidative stress plays a major role in both circumstances. Copper deficiency can contribute to the development and progression of cardiovascular disease and diabetes [5]. Copper NPs showed antidiabetic and antioxidant properties [6]. In addition, copper NPs are used as antibacterial and antifungal agents [7]. So, are copper NPs problem makers or problem solvers? In this mini-review the various aspects of copper NPs will be discussed. Synthesis Copper NPs are very attractive due to their high thermal conductivity and relatively low costs compared to e.g. gold and silver nanoparticles. They can be synthesized by physical, chemical and green techniques. Vacuum vapor deposition, pulsed laser ablation, pulsed wire discharge and mechanical wiring are physical techniques Chemical reduction ,microemulsion techniques, sonochemical reduction, electrochemical, microwave assisted and hydrothermal are chemical approaches for the synthesis of copper nanoparticles [4,5,8]. Green synthesis of copper NPs is using different plants, bacteria and fungi [9,10]. Characteristics The properties of copper NPs depend largely on size, structure, shape ,surface properties, particle aggregation, agglomeration and optical characteristics. Their catalytic activity increases with the decrease in size of copper NPs [11]. Catalytic activity Catalysts are substances that promote and accelerate chemical reactions without being consumed. Catalysis based on copper NPs may benefit for example the synthesis of methanol or the production of hydrogen on an industrial scale [11-13]. Antibacterial/Antifungal action It has been known for a long time that copper and copper alloys have antimicrobial properties [14]. Copper has two key properties that are exploited in consumer products and medical devices. Copper has potent biocidal properties and is critical for most tissues including the skin. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis [14]. It is therefore not surprising these properties are leveraged of copper-oxide NPs impregnated wound dressings [14-17]. Copper has antimicrobial activities against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, vancomycin- Mini Review Novel Techniques in Nutrition and Food Science C CRIMSON PUBLISHERS Wings to the Research 243 Copyright © All rights are reserved by Michael AB Naafs. Volume - 3 Issue - 2 Abstract In this mini-review various aspects of copper nanoparticles are considered with a special emphasis on antioxidant stress. Copper nanoparticles may become a problem maker for the environment but seems a problem solver in wound dressings and potentially in diabetes and cancer. Long- term toxicity of copper nanoparticles is not known. An international registry agency should control the use of copper nanoparticles, especially in food nanotechnology. ISSN: 2640-9208
  • 2. Nov Tech Nutri Food Sci Copyright © Michael AB Naafs 244 How to cite this article: Michael AB N.Copper Nanoparticles and Antioxidant Stress: Problem Makers or Solvers?. Nov Tech Nutri Food Sci. 3(2). NTNF.000557. 2019. DOI: 10.31031/NTNF.2019.03.000557 Volume - 3 Issue - 2 resistant enterococci (VRE) and ESBL-producing species as well as adenoviruses, Influenza A and fungi [14,18]. Cytotoxicity Elevated copper levels result in the loss of membrane integrity, which causes essential nutrients, including potassium and glutamate to leak from cells and cause apoptosis [14]. Shafagh et al. [19] studied cytotoxicity and apoptosis of copper oxide NPs on a chronic myeloid leukemia (CML) K562 cell line. CuO NPs showed selectivity towards the K562 cell line and are potentially a good anti-cancer drug since it does not kill healthy cells. Apoptosis is mediated through reactive oxygen species (ROS) production in cancer cells, starting with P53 up-regulation [19]. Copper NPs also induced apoptosis in a human skin melanoma cell line [20]. Similar findings have been reported in a glial cancer cell line by Kukia et al. [21]. Antioxidant activity Copper oxide (CuO) NPs have higher toxic effects than Cu NPs due to its oxidative property. CuO NPs stimulate photosynthesis at low concentrations (<0.25mg/L) but suppression of photosynthesis was observed at 1mg/L concentration. CuO NPs have been shown to enhance the production of reactive oxygen species (ROS). At low copper concentrations these ROS’ are protective in plants, but at high Cu concentrations they may be cytotoxic and lead to apoptosis, as mentioned before [4,22]. In addition, phytohormones were also observed to be altered as a response to CuO NPs [23]. Most studies of the antioxidant effects of Cu NPs have been done in animals [4]. The effect of antioxidant stress on cytochrome P450 and liver disease has been studied in rats and in cancer cell lines [24,25]. In humans, curcumin Cu NPs have been studied mostly for their potential anti-cancer activity [26,27]. Although curcumin has been strongly advocated as a natural antioxidant in vitro, in vivo and clinical studies are not able to provide evidence for a significant role in the prevention of cancer. Even with modern curcumin nano- formulations poor curcumin bioavailability could not be overcome [28]. Metabolic disease Nanotechnology has been used in diagnosing and monitoring of diabetes by sensor technology [29,30]. Ghosh et al. [6] suggested an antidiabetic effect of copper NPs by inhibiting the enzyme alpha-glucosidase. Javed et al. [31] believe that copper NPs can have hypoglycemic properties. Recently, it has been reported that patients with metabolic syndrome need more vitamin C to break the cycle of antioxidant depletion [32]. It is very well possible that the antidiabetic effects of copper NPs are achieved by restoring vitamin C mediated antioxidant depletion in the metabolic syndrome. Therefore, it is interesting to know that CU NPs can be prepared with ascorbic acid (vitamin C) by an aquous solution reduction method [33]. It has also been known that vitamin C depletion lowers the uptake of copper [34]. Conclusion It is obvious that the widespread use of copper NPs in all kind of sectors can lead to large environmental problems. The use of these NPs has not been regulated and toxicity is not known for the long term. Accumulation in the environment has clear toxic effects on plants when these NPs are used in pesticides and fertilizers. Detection of Cu NPs in the environment is extremely difficult [35] and therefore copper NPs could be problem makers in the long term. Long-term toxicity in humans is not known and an international registry agency covering the use of NPs and Cu NPs should be instituted therefore, especially for food nanotechnology [28]. On the other hand, the use of Cu NPs in wound dressing and diabetes sensor technology ,as well as their antimicrobial spectrum are of proven benefit [14-18,30]. So, they are problem solvers, too. The anti-cancer activity still has a potential future in nanomedicine and has been explored not enough, yet. So, there has to be done still much more research in the ecological effects of NPs, in nanomedicine and especially in food nanotechnology.. References 1. Mosa KA, El-Naggar M, Ramamoorthy K, Alawadhi H, Elnaggar A, et al. (2018) Copper nanoparticles induced genotoxicity, oxidative stress, and changes in superoxide dismutase (SOD) gene expression in cucumber (Cucumis sativus) plants. Front Plant Sci 9: 872. 2. Gupta YR, Sellegoander D, Kannan M, Deepa S, Senthilkumaran B, et al. 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