Alterations In Antioxidant Defense System Research Articles

Mitotherapy with Fresh Isolated Cardiac Mitochondria Via Injection Into Blood Reduces Aluminum Phosphide-Induced Mortality and Protects Cardiac Tissue Against Oxidative Stress and Mitochondrial Damages.

The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning.

Chitosan-enhanced heat tolerance associated with alterations in antioxidant defense system and gene expression in creeping bentgrass

Chitosan-enhanced heat tolerance associated with alterations in antioxidant defense system and gene expression in creeping bentgrass

Inhibition of mitochondrial permeability transition pore and antioxidant effect of Delta-9-tetrahydrocannabinol reduces aluminium phosphide-induced cytotoxicity and dysfunction of cardiac mitochondria

Previous studies have demonstrated that phosphine gas (PH3) released from aluminium phosphide (AlP) can inhibit cytochrome oxidase in cardiac mitochondria and induce generation of free radicals, oxidative stress, alteration in antioxidant defense system and cardiotoxicity. Available evidence suggests that cannabinoids have protective effects in the reduction of oxidative stress, mitochondrial and cardiovascular damages. The objective of this study was to evaluate the effect of trans-Δ-9-tetrahydrocannabinol (THC) on AlP-induced toxicity in isolated cardiomyocytes and cardiac mitochondria. Rat heart isolated cardiomyocytes and mitochondria were cotreated with different concentrations of THC (10, 50 and 100 μM) and IC50 of AlP, then cellular and mitochondrial toxicity parameters were assayed. Treatment with AlP alone increased the cytotoxicity, depletion of cellular glutathione (GSH), mitochondrial reactive oxygen species (ROS) generation, lipid oxidation, mitochondria membrane potential (ΔΨm) collapse and mitochondrial swelling, when compared to control group. However, incubation with THC (10, 50 and 100 μM) attenuated the AlP-induced changes in all these parameters in a THC concentration-dependent manner. Interestingly, the obtained results showed remarkably significant protective effects of THC by attenuation the different parameters of cytotoxicity, mitochondrial toxicity and oxidative stress induced by ALP in isolated cardiomyocytes and cardiac mitochondria. It is the first report showing the protective effects of THC against AlP-induced toxicity, and these effects are related to antioxidant potential and inhibition of mitochondria permeability transition (MPT) pore. Based on these results, it was hypothesized that THC may be used as a potential therapeutic agent for the treatment of AlP-induced mitochondrial dysfunction and cardiotoxicity.

Protective Effect of Melatonin Against Malathion Induced Alterations in Antioxidant Defense System and Morphology of Erythrocytes in Wistar Rats

Malathion intoxication has been shown to produce oxidative stress due to the generation of free radicals and alter the antioxidant defense system in erythrocytes. Previous studies have shown the ameliorative role melatonin against oxidative stress induced by generation of free radicals. Present study was designed to investigate the protective effect of melatonin against malathion induced oxidative stress. For this purpose, male Wistar rats were randomly divided into four groups: Control; Melatonin (10mg/Kg body weight) group; Malathion (250mg/Kg body weight) treated group; Malathion + Melatonin treated group. Animals were administered an acute dose of malathion orally. The result of this study shows that in vivo administration of malathion caused inhibition in AChE activity in erythrocytes. Malathion intoxication also significantly increased the oxidative damage as evidenced by increased level of LPO and GSH content. The Inhibition of GSH level and increased lipid peroxidation in erythrocytes was relieved in malathion + melatonin group. Enhanced activities of SOD, CAT, GR and GPx were observed in erythrocytes of malathion treated rats as compared to control group. Moreover, melatonin supplementation in malathion treated rats maintain normal level of antioxidant enzymes as compared to malathion treated rats which indicates that melatonin provide protection against malathion-induced oxidative stress in erythrocytes. No significant change in the membrane bound enzymes such as Na+/K+-ATPase, Mg2+-ATPase and Ca2+-ATPase was observed in malathion intoxicated rats. Findings of scanning electron micrographs of erythrocytes revealed that both the malathion treated and malathion+melatonin treated groups exhibited morphological changes in erythrocytes. However, concomitant melatonin supplementation normalized the morphological alterations in erythrocytes induced by malathion toxicity. In conclusion, melatonin supplementation may ameliorate malathion-induced oxidative imbalance by enhancing the glutathione level, reducing lipid peroxidation and normalizing antioxidant enzyme activities in erythrocytes.

Alteration in Antioxidant Defense System and Oxidative Stress in blood for Non Alcoholic Fatty Liver Disease

Alteration in Antioxidant Defense System and Oxidative Stress in blood for Non Alcoholic Fatty Liver Disease

Microcystin-LR leads to oxidative damage and alterations in antioxidant defense system in liver and gills of Brycon amazonicus (SPIX & AGASSIZ, 1829)

Microcystin's (MCs) are toxins produced by several groups of cyanobacteria, in water bodies throughout the world, in a process which is being intensified by human action. Among the variants of MCs, MC-LR stands out for its distribution and toxicity. MCs are potent inhibitors of protein phosphatases 1 and 2 A, which causes disruption of the cytoskeleton and consequent cell death. They can also alter the antioxidant system and induce oxidative stress in various organs of many species. There is, however, a lack of information about the effects of MCs on the antioxidant system and oxidative damage in Brazilian fishes. This study evaluated the effect of microcystin-LR on the antioxidant system in liver and gills of the Brazilian fish Brycon amazonicus, after 48 h of i.p injection of 100 μg MC-LR.kg−1 body mass. The liver exhibited increases in the activity of GST (74%) and GPx (217%), and a 47% decrease in SOD activity, with no changes in CAT values. In the gills of fish exposed to MC-LR, CAT and GPx activities did not show significant changes, while SOD and GST activity decreased by 66% and 37%, respectively. The GSH content did not change significantly in the liver, however, a decrease of 43% was observed in the gills. Oxidative damage measured by protein oxidation (PC) and lipoperoxidation (LPO) showed significant effects in both tissues. In hepatic tissue, there was no change in PC levels but LPO increased by 116%. Conversely, in the gills LPO levels did not change but PC increased by 317%. In conclusion, these data show that MC-LR induces oxidative damage in both tissues but in different ways, with being liver most sensitive to LPO and gills to PC. This also suggests that the gills are most sensitive to oxidative stress than liver, due to the inhibition of its antioxidant responses following MC-LR exposure.

Changes of Antioxidant Defense System and Fatty Acid Composition in Bermudagrass under Chilling Stress

Bermudagrass (Cynodon dactylon) is a typical and widely used warm-season turfgrass. Low temperature is one of the key environmental stress limiting its utility. However, little information is available about the differences of cold response between bermudagrass genotypes. Here, we analyzed antioxidant defense system and fatty acid composition in cold-resistant genotype WBD128 and cold-sensitive genotype WBDg17 exposed to chilling stress. Low temperature (4 °C) significantly decreased the relative water content, whereas increased the H2O2 and O2− contents, more profoundly for WBDg17. Under chilling condition, WBD128 had higher anti O2− activity than WBDg17. Besides, the contents of total glutathione, reduced glutathione (GSH) and its oxidized form (GSSG) were markedly increased by low temperature in both genotypes, whereas WBD128 had significantly higher values of GSH, total glutathione, and GSH/GSSG ratio than WBDg17. Moreover, chilling stress increased saturated fatty acids (SFAs) percentage (palmitic acid and stearic acid) in WBDg17. After chilling treatment, the proportion of linoleic acid decreased in both genotypes, particularly in WBDg17. As for unsaturated fatty acids (UFAs), the percentage of linolenic acid was increased in WBD128. In addition, chilling treatment decreased the values of double bond index (DBI), UFA/SFA ratio as well as degree of unsaturation in WBDg17. Finally, chilling stress altered the expression patterns of the genes, which encode one kind of late embryogenesis abundant proteins (LEA), superoxide dismutase (Cu/Zn SOD) C-repeat-binding factor/DRE-binding factor (CBF1), and peroxidase (POD-2). Collectively, our results revealed that natural variation of chilling tolerance in bermudagrass genotypes may be largely associated with the alterations of antioxidant defense system and fatty acid composition.

Ameliorative effects of curcumin against lead induced toxicity in human peripheral blood lymphocytes culture

Lead, a heavy metal and multifaceted toxicant, is well studied for its distribution and toxicity in ecosystem, yet there is no consensus on its amelioration by any synthetic or phytochemical compounds. Curcumin, a known antioxidant and dietary element, is a well-known herb, for its therapeutic uses and having a wide spectrum of its beneficial properties against several adverse effects. Hence, the current study was taken into consideration to evaluate the ameliorative effects of curcumin (3.87 μM, i.e. 1.43 μg/ml) against lead acetate (doses: 10−6 M, i.e. 0.379 μg/ml and 10−4 M, i.e. 37.9 μg/ml, durations: 24 h and 69 h) induced genotoxicity and oxidative stress in human peripheral blood lymphocyte cultures (PBLC). On one hand, antigenotoxic and antioxidative potentials of curcumin against lead were simultaneously evaluated by the array of genotoxicity and oxidative stress indices. The result postulated that lead acetate showed dose- and duration-dependent increase in both genotoxicity and oxidative stress whereas curcumin, when added along with lead acetate, showed the significant amelioration in all genotoxic and oxidative stress-related indices. The study indicated that, due to alteration in antioxidant defense system, there is an adverse genotoxic effect of lead. On the other hand, curcumin, a potent antidote, can protect chromatin material against lead -mediated genotoxicity by balancing the activity of antioxidant defense system.

In Vitro Amelioration by Curcumin on Genotoxicity in Workers with Elevated Blood Cadmium Level

Curcumin is a dietary element, easily available and also well-known herb, for its therapeutic uses. On the other hand, cadmium is considered as an omnipresent, hazardous, heavy metal as well as known carcinogen, clastogen and mutagen. It is known to produce severe toxic effects during occupational exposure in industries related to nickel-cadmium batteries, pigments, chemical stabilizers, metal coatings and alloys in humans. So, the objective of this study was to evaluate the ameliorative effects of curcumin as an antioxidant agent against cadmium induced genotoxicity in Peripheral Blood Lymphocyte Cultures (PBLC) of occupationally cadmium exposed individuals. The blood cadmium level was determined and it was significantly higher in exposed individuals as compared to controls. Blood samples from 40 workers exposed to cadmium, and 40 unexposed controls were used to analyse biochemical parameters like Total protein, GSH, GPx, GR, GST, LPO, CAT and SOD along with genotoxic parameters like SCEs, CCPI, AGT and PDT. The study revealed cadmium induced the free radicals formation which caused alteration in antioxidant defense system and may lead to genotoxicity. While curcumin ameliorates this toxicity by balancing the antioxidant defense system, decrease the lipid peroxidation and ultimately protect cells against cadmium genotoxicity. Hence, it can be concluded that curcumin which is herbal antidote can be helpful to protect cadmium toxicity in occupationally exposed workers.

Alterations in antioxidant defense system in hepatic and renal tissues of rats following aspartame intake

Aspartame is one of the most common artificial sweeteners in use today worldwide. Aspartame has been implicated in many health problems. The study aimed to investigate whether aspartame consumption induces oxidative stress and whether it can threaten the antioxidant defense system in hepatic and renal tissues. The experiment was performed on adult male albino rats. They were distributed into 4 groups, group I represented the control animals and received orally water. The rest were given aspartame in a dose 50 mg/kg for 15, 30 and 60 days respectively. Blood was collected and centrifuged to obtain serum for the determination of serum enzymes. The tissue samples were homogenized, centrifuged and the clear supernatant was collected for further biochemical analysis. The results showed a significant increase in LPO level in liver and kidney. A remarkable reduction in GSH content was also observed in both hepatic and renal tissues. The activities of antioxidant enzymes SOD, CAT, GPx and GR were significantly reduced in both liver and kidney. In addition, the results also indicated a significant increase in activities of serum marker enzymes ALT, AST, ALP and GGT. The data provided in this study clearly point out that aspartame consumption at a dose of 50 mg/kg induces oxidative stress in hepatic and renal tissues by generation of free radicals.

Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline.

Doxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders. One of the factors influencing the photosensitivity reactions is the melanin content in melanocytes. In this study, the impact of doxycycline and UVA irradiation on cell viability, melanogenesis and antioxidant defense system in cultured normal human epidermal melanocytes (HEMn-DP) was examined. The exposure of cells to doxycycline and UVA radiation resulted in concentration-dependent loss in melanocytes viability and induced melanin biosynthesis. Significant changes were stated in cellular antioxidant enzymes activity: SOD, CAT and GPx, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation.

Developmental exposure to manganese induces lasting motor and cognitive impairment in rats

Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20mg/kg/day) from post-natal day (PND) 8–12. Behavioral tests were performed on PND 60–65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum.

Effect of tetracycline and UV radiation on melanization and antioxidant status of melanocytes

Tetracycline is a semisynthetic antibiotic and is used in several types of infections against both gram-positive and gram-negative bacteria. This therapy is often associated with phototoxic reactions that occur after exposure to UV radiation and lead to photo-onycholysis, pseudoporphyria, solar urticaria and the fixed drug eruption in the skin. The phototoxic reactions may be related to the melanin content which, on one side may bind drugs – leading to their accumulation, and on the other side, they have photoprotective and antioxidant properties.In this study the effect of tetracycline and UVA irradiation on cell viability, biosynthesis of melanin and antioxidant defense system in cultured normal human epidermal melanocytes (HEMn-DP) was analyzed. The viability of the cells treated with tetracycline and exposed to UVA radiation decreased in a drug concentration-dependent manner. At the same time, the induction of the melanization process was observed. The significant alterations in antioxidant defense system, on the basis of changes in SOD, CAT and GPx activities, were stated. The obtained results may give explanation for the phototoxic effects of tetracycline therapy observed in skin cells exposed to UVA radiation.

Age-dependent alteration of antioxidant defense system in hypertensive and type-2 diabetes patients.

BackgroundThe association between hypertension and diabetes has been linked to increased oxidative stress with age. This study was to examine the level of age-dependent alterations in antioxidant defense system between patients having hypertension and/or type-2 diabetes.MethodsThe study was conducted at the Ahmadu Bello University Teaching Hospital, Zaria-Nigeria, using 200 Subjects recruited from the cardiology, endocrinology and outpatient clinics. They were divided into four groups of 50 subjects each, namely: Diabetic group (DG), hypertensive (HG) and hypertensive-diabetic group (HDG) as cases. The control group (CG) was non-diabetic normotensive subjects. They were all stratified into six age-ranges namely 20–29, 30–39, 40–49, 50–59, 60–69, 70–79 years. Oxidative stress markers (lipid peroxidation, antioxidant vitamins and elements, enzymatic and non-enzymatic antioxidant) were measured in the blood sample collected from all subjects in each age group within the study groups.ResultsThe results in the DG, HG and HDG, showed that the percentage decrease in enzymatic antioxidants and antioxidant vitamins with age were significantly (P < 0.05) higher than 10.8% and 20.0% respectively when compared to the CG, whereas, the level of decrease in serum Selenium at same age range was significantly higher than 52.8%. The level of lipid peroxidation in the cases was observed to be significantly (P < 0.05) higher than 89.9% when compared to the mean reference values (2.94 ± 0.05 nmol/ml) of the CG at same age range. Also, the decrease levels of endogenous antioxidants were observed to be directly related to aging.ConclusionThe result obtained demonstrates the percentage age-dependent alteration in oxidative stress markers. The percentage decrease in the antioxidant levels during aging could be an explanation to the possible link, underlying the complication of type-2 diabetes and hypertension in this locale. Hence, antioxidants supplements may be useful in the management of the diseases during aging.

Alterations in antioxidant defense system of workers chronically exposed to arsenic, cadmium and mercury from coal flying ash.

Humans are exposed to different stress factors that are responsible for over-production of reactive oxygen species. Exposure to heavy metals is one of these factors. The aim of the study was to analyze the effect of chronic exposure to heavy metals through coal flying ash on the efficiency of antioxidative defensive mechanisms, represented by the activity of superoxide dismutase, glutathione peroxidase and ascorbic acid. Nonessential elements such as arsenic and mercury levels showed a significant increase (p>0.001) in the power plant workers rather than in the control subjects. There were no significant differences of blood cadmium between power plant workers and control subjects. We found a significant positive correlation (p<0.05) between BAs/SZn (r=0.211), BAs/BSe (r=0.287), BCd/SCu (r=0.32) and BHg/BSe (r=0.263) in the plant workers. Red blood cell antioxidant enzymes and plasma ascorbic acid were significantly lower in power plants workers than in the control group (p<0.002). We can conclude that levels of mercury, arsenic and cadmium in blood, despite their concentration within the reference values, significantly affect plasma ascorbic acid concentration, superoxide dismutase and glutathione peroxidase activity, which are able to increase the risk of oxidative stress.

Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus.

Objective:Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats.Materials and Methods:Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were administered with 25, 50 and 75 mg/kg body weight blend of sunset yellow, metanil yellow and tartrazine for 30 days. Hepatotoxicity in rats treated with a blend of these food colors was studied by assessing parameters such as serum total protein, serum albumin, serum alkaline phosphatase (ALP) as well as hepatic malondialdehyde (MDA). The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were assessed.Results:Significantly increased concentrations of serum total protein, serum albumin, serum ALP and hepatic MDA and significantly lowered levels of SOD, reduced GSH and CAT in the liver tissue of treated animals were observed when compared with control animals. The alteration in the liver includes necrosis of hepatocytes, infiltration and vacuolation.Conclusion:The result indicates that consumption of food color in diet induces liver tissue damage. The used doses of food color were mostly attributable to hepatocellular damage and drastic alteration in antioxidant defense system.

Alteration in anti-oxidant defense system and protein expression in response to varied concentrations of EMS in Psoralea corylifolia

Germplasm of Psoralea corylifolia L., one of the most important endangered medicinal plants of Chinese and Indian Pharmacopeia were treated with ethyl methane sulphonate (0, 0.1, 0.25, 0.50, 0.75 and 1 %) and sampled for observations in the form of growth, non enzymatic systems and stress proteins at pre-and post-flowering stages of development. Higher concentrations of EMS showed significant (P < 0.001) inhibition in the germination percentage from 3.88 to 35.46 % at pre-flowering stage and from 4.90 to 35.97 % at post-flowering stage when compared to control. Other growth related parameters viz shoot growth and root growth also declined within increase in the dose as compared to control plants. Root growth was severely affected as compared to shoot growth. Roots showed a significant correlation with tolerance index as increasing concentration of EMS progressively inhibited the root growth. Plants developed from treated germplasm at higher doses exhibit higher activity of ascorbate peroxidase (APX), up to flowering and after that declined. Contrast to that, total soluble protein (TSP) content decreased in age and dose wise manner. The EMS dose applied and oxidative stress was correlated and derived from the increased antioxidant activities and decrease in total glutathione content from 122.75 % (GSH) and 103.29 % (GSSG) in plants raised from treated germplasm towards the post-flowering stage. Pronounced accumulation of psoralen from 10.74 to 93.24 % was observed following higher doses of EMS at post-flowering stage, where EMS induced oxidative stress-enhanced proline accumulation and lipid peroxidation. In addition, the prevalence of maximum antioxidant activity, psoralen accumulation was an efficient process in acclimatizing P. corylifolia to stress. 2-Dimensional gel electrophoresis (2D-GE) of the protein expression profile and MALDI TOF–MS revealed an expression of 20 different proteins which are associated with such functions as cellular detoxification, stress defense, psoralen production, photosynthesis, signal transduction, and cell cycle. The increase in the psoralen pool after EMS treatment proved to be a best protective antioxidant to counterbalance EMS-induced ROS detoxification and can be used as a biomarker and a scavenger in stress physiology.

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be 7.43mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine.

Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines

It is well known the participation of oxidative stress in the induction and development of different pathologies including cancer, diabetes, neurodegeneration and respiratory disorders among others. It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. Large number of registered products containing chlorpyrifos (CPF) is used to control pest worldwide. We have previously reported that 50μM CPF induces ROS generation and produces cell cycle arrest followed by cell death. The present investigation was designed to identify the pathway involved in CPF-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, we determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. Finally we studied the molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide.In this study we demonstrate that CPF (50μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. Furthermore, we found that the main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. As PD98059 could not abolish the increment of ROS induced by CPF, we concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.

Nicotine impact on melanogenesis and antioxidant defense system in HEMn-DP melanocytes.

Nicotine is a compound of tobacco plants and is responsible for addictive properties of tobacco which is used by about one billion of smokers all over the world. Recently, nicotine has drawn even more attention due to its presumed neuroprotective and antioxidant features as far as common use in various forms of smoking cessation therapies. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn influence biochemical processes in human cells producing melanin. The aim of this study was to examine the impact of nicotine on melanogenesis and antioxidant defense system in cultured normal human melanocytes (HEMn-DP). Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be 2.52 mM. Nicotine modulated melanin biosynthesis in normal human melanocytes. Significant changes in hydrogen peroxide content and cellular antioxidant enzymes: SOD, CAT, and GPx activities were stated in melanocytes exposed to nicotine, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long-term exposition to nicotine.