Changes in antioxidant enzymes in humans with long-term exposure to pesticides

Different pesticides, including organophosphates (OPs), have been reported to induce oxidative stress due to generation of free radicals and alteration in antioxidant defence mechanisms. In this study, a cohort of 81 intensive agriculture workers (pesticide sprayers) was assessed twice during the course of a spraying season for changes in erythrocyte antioxidant enzymes. Acetylcholinesterase (AChE) was used as a reference biomarker. Sprayers presented lower levels of superoxide dismutase (SOD) and glutathione reductase (GR) as compared to controls independently of age, BMI, smoking habit or alcohol consumption. A positive correlation between SOD and AChE was observed at the high exposure period. Those individuals with a decrease in AChE greater than 15% exhibited lower SOD and catalase (CAT) activities at the same period. Glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) remained unaffected in the exposed population. Paraoxonase (PON1) polymorphism influenced erythrocyte CAT and GR, as subjects with the R allele presented lower CAT and higher GR levels. Whether or not the decreased enzyme activities found in this study are linked to the adverse health effects related to chronic pesticide toxicity (in which oxidative damage plays a pathophysiological role, such as cancer or neurodegenerative disorders) is an attractive hypothesis that warrants further investigation.     

Environmental tobacco smoke induces oxidative stress in distinct brain regions of infant mice

Environmental tobacco smoke (ETS) leads to the death of 600,000 nonsmokers annually and is associated with disturbances in antioxidant enzyme capacity in the adult rodent brain. However, little is known regarding the influence of ETS on brain development. The aim of this study was to determine levels of malonaldehyde (MDA) and 3-nitrotyrosine (3-NT), as well as enzymatic antioxidant activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD), in distinct brain structures. BALB/c mice were exposed to ETS twice daily for 1 h from postnatal day 5 through postnatal day 18. Acute exposure was performed for 1 h on postnatal day 18. Mice were euthanized either immediately (0) or 3 h after the last exposure. Immediately after an acute exposure there were higher GR and GST activities and MDA levels in the hippocampus, higher GPx and SOD activities in the prefrontal cortex, and higher GST activity and MDA levels in the striatum and cerebellum. Three hours later there was an increase in SOD activity and MDA levels in the hippocampus and a decrease in the activity of all enzymes in the prefrontal cortex. Immediately after final repeated exposure there were elevated levels of GST and GR activity and decreased GPx activity in the hippocampus. Moreover, a rise was found in GPx and GST activities in the prefrontal cortex and increased GST and GPx activity in the striatum and cerebellum, respectively. After 3 h the prefrontal cortex showed elevated GR and GST activities, and the striatum displayed enhanced GST activity. Data showed that enzymatic antioxidant system in the central nervous system responds to ETS differently in different regions of the brain and that a form of adaptation occurs after several days of exposure.     

Zinc supplementation ameliorates static magnetic field-induced oxidative stress in rat tissues

The present study was undertaken to find out the effect of zinc supplementation on the antioxidant enzymatic system, lipid peroxidation and DNA oxidation in liver and kidney of static magnetic field (SMF) exposed rats. The exposure of rats to SMF (128mT, 1h/day during 30 consecutive days) decreased the activities of glutathione peroxidase (GPx), catalase (CAT) and the superoxide dismutase (SOD) in liver and kidney. By contrast, sub-chronic exposure to SMF increased the malondialdehyde (MDA) concentration in liver and kidney. Our results revealed an increase of the 8-oxo-7,8-dihydro-2'-desoxyguanosine (8-oxodGuo) in kidney of SMF-exposed rats. However, this biomarker of DNA oxidation remained unchanged in liver. Zinc supplementation (ZnCl(2), 40mg/l, per os) in SMF-exposed rats restored the activities of GPx, CAT and SOD in liver to those of control group. However, only CAT activity was restored in kidney. Moreover, zinc administration was able to bring down the elevated levels of MDA in the liver but not in the kidney. Interestingly, zinc supplementation attenuated DNA oxidation induced by SMF in kidney to the control level. Our investigations suggested that zinc supplementation minimizes oxidative damage induced by SMF in rat tissues.     

Repeated acetaminophen dosing in rats: adaptation of hepatic antioxidant system

Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease their sensitivity to its hepatotoxic effects, which are associated with oxidative stress and glutathione depletion. We determined if repeated acetaminophen dosing produced adaptive response of key antioxidant system enzymes. Male rats (Sprague-Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral gavage for 4 days. Liver was assayed for oxidative stress and antioxidant markers: malondialdehyde (MDA), thiobarbituric acid reactive substance (TBARS), total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker of hepatocellular injury. Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%, GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91; SOD, r=0.66; GPx, r=0.45). Despite antioxidant deficiencies, and no TBARS change, MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased GR (61%/62%/76%, r=0.77) and G6PD (130%/110%/190%, r=0.78). Both MDA (r=0.68) and G6PD (r=0.71) correlated with hepatic ALT, which decreased 27%/43%/48%, respectively. Resistance to acetaminophen hepatotoxicity produced by repeated exposure is partially attributable to upregulation of hepatic G6PD and GR activity as an adaptive and protective response to oxidative stress and glutathione depletion.     

Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects

Cyanide-induced chemical hypoxia is responsible for pronounced oxidative damage in the central nervous system. The disruption of mitochondrial oxidative metabolism has been associated with upregulation of uncoupling proteins (UCPs). The present study addresses the dose- and time-dependent effect of sub-acute cyanide exposure on various non-enzymatic and enzymatic oxidative stress markers and their correlation with inducible-nitric oxide synthase (iNOS) and uncoupling protein-2 (UCP-2) expression. Animals received (oral) triple distilled water (vehicle control), 0.25 LD50 potassium cyanide (KCN) or 0.50 LD50 KCN daily for 21 d. Animals were sacrificed on 7, 14 and 21 d post-exposure to measure serum cyanide and nitrite, and brain malondialdehyde (MDA), reduced glutathione (GSH), glutathione disulfide (GSSG), cytochrome c oxidase (CCO), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CA) levels, together with iNOS and UCP-2 expression, and DNA damage. The study revealed that a dose- and time-dependent increase in cyanide concentration was accompanied by corresponding CCO inhibition and elevated MDA levels. Decrease in GSH levels was not followed by reciprocal change in GSSG levels. Diminution of SOD, GPx, GR and CA activity was congruent with elevated nitrite levels and upregulation of iNOS and UCP-2 expression, without any DNA damage. It was concluded that long-term cyanide exposure caused oxidative stress, accompanied by upregulation of iNOS. The upregulation of UCP-2 further sensitized the cells to cyanide and accentuated the oxidative stress, which was independent of DNA damage.     

Effect of wastewater intake on antioxidant and marker enzymes of tissue damage in rat tissues: Implications for the use of biochemical markers

In the present study, alteration in antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) and marker enzymes of tissue damage alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) with laboratory exposure to wastewaters from Aligarh (AWW) and Saharanpur (SWW) were investigated in rat liver and kidney. Levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydrogen peroxide (H₂O₂) were also determined.A profound enhancement of 5 and 2.5-folds in MDA level was recorded in the liver and kidney respectively as a result of oral administration of SWW to the rats. Exposure to both AWW and SWW resulted in 3–4-fold increase in GR activity and 3-fold increase in SOD and ALT activity in the hepatic tissue compared to control values. Ingestion of AWW and SWW resulted in 3.5-fold rise in renal AST levels whereas AWW caused 75% decline in GST activity in kidney of treated rats.Results indicate that wastewater (AWW/SWW) caused severe damage to renal and hepatic tissues and the effect seems in part to be mediated by suppression of antioxidant system with GR and SOD as potential candidates for hepatic toxicity biomarkers of wastewaters.     

Effects of verbascoside and luteolin on oxidative damage in brain of heroin treated mice

Extensive but fragmentary studies have shown: (i) heroin, morphine and opiates are able to induce reactive oxygen species (ROS) formation in several cells, (ii) they decrease the antioxidant defense system including enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and antioxidants, glutathione (GSH), Se, and vitamins. This study is to investigate the oxidative damage to DNA, proteins, and lipids in brain of mice administered heroin via intraperitoneal injection, and the effects of verbascoside and luteolin on this damage. All the indices of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl group and malondialdehyde (MDA) contents increased significantly compared to those of controls in the brains of heroin-administered mice, while the indices related to the in vivo antioxidative capacity, such as the ratio of GSH and oxidized glutathione (GSSG), and activities of SOD, CAT and GPx in the brain, and total antioxidant capacity (TAC) in serum significantly decreased. When heroin-dependent mice were treated with verbascoside or luteolin, oxidative stress status was limited.     

Evidences for a role of glutathione peroxidase 4 (GPx4) in methylmercury induced neurotoxicity in vivo

We evaluated the activity and expression of antioxidant enzymes in the cerebellum and cortex of Swiss adult male mice exposed to methylmercury (MeHg) in drinking water (40mg/L) during 21 days. The activity of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and thioredoxin reductase (TrxR) were determined spectrophotometrically. The expression (protein levels) of GPx1 and GPx4 isoforms, TrxR1 as well as heat shock protein 70 (HSP70) were evaluated using specific antibodies and normalized by actin levels. The exposure of mice to MeHg caused a significant impairment in locomotors performance in the open field test (crossings and rearing). This result was followed by a significant reduction of GPx and TrxR activities in the cerebellum and cortex when compared to untreated animals. We also observed a substantial decrease in GPx1, GPx4 and TrxR1 protein levels in the cerebellum, while in the cerebral cortex, only GPx4 and TrxR1 were decreased after MeHg treatment. The activities of the antioxidant enzymes GR, GST, CAT and SOD were increased in the cerebellum after MeHg administration to mice. In contrast, only CAT was increased in the cerebral cortex of MeHg-treated animals. The expression of HSP70 was up-regulated only in the cerebellum where MeHg-exposed mice showed a significant increase in the immunocontent of HSP70 when compared to controls. This is the first report showing a role for GPx4 in the neurotoxicity induced by MeHg in vivo. In addition, our data indicates that the selenoproteins GPx and TrxR as main targets during MeHg exposure, which may be considered in biomarker studies.     

Protective effect of protexin concentrate in reducing the toxicity of chlorpyrifos in common carp (Cyprinus carpio)

The present study aimed to evaluate the protective effect of protexin supplementation against chlorpyrifos-induced oxidative stress and immunotoxicity in Cyprinus carpio. After 21 days, the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR), and total antioxidant levels significantly decreased in hepatocytes of fish exposed to chlorpyrifos, while malondialdehyde (MDA) increased. Treatment with protexin was able to reverse the decrease in SOD and GR and significantly reduce MDA levels. Exposure to chlorpyrifos also induced alterations in blood biochemical parameters and caused immunosuppression. Dietary protexin return some parameters (aspartate aminotransferase, lactate dehydrogenase, and γ-glutamyltransferase activities, and glucose, cholesterol, total protein, creatinine, and complement C4 levels) to values similar to those of the control group. Based on the results, it can be concluded that protexin exerted protective effects against chlorpyrifos exposure in C. carpio reducing oxidative damage, and ameriorating blood biochemical alterations and the immunosuppression.     

Antioxidant effects of fermented sea tangle (Laminaria japonica) by Lactobacillus brevis BJ20 in individuals with high level of γ-GT: A randomized, double-blind, and placebo-controlled clinical study

A randomized, double-blind, and placebo-controlled clinical study was performed to evaluate the antioxidant effects of fermented sea tangle (FST) on healthy volunteers with high levels of γ-glutamyltransferse (γ-GT). Forty-eight participants were divided into a placebo group and an FST group that received FST (1.5 g/day) for 4 weeks. Serum γ-GT, malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined before and after the trial. Administering FST significantly decreased serum levels of γ-GT and MDA. Additionally, SOD and CAT activities were significantly augmented compared to those in the placebo group after 4 weeks, but no significant alteration was observed in GPx activity compared to that in the placebo group. Our findings indicate that FST enhanced the antioxidant defense system in a healthy population and may be useful as a functional food ingredient.     

Malathion-induced oxidative stress in human erythrocytes and the protective effect of vitamins C and E in vitro

Malathion is an organophosphate (OP) pesticide that has been shown to induce oxidative stress in erythrocytes through the generation of free radicals and alteration of the cellular antioxidant defense system. We examined the effect of several different doses of malathion (25, 75, 200 microM), or malathion in combination with vitamin C (VC; 10 microM) or vitamin E (VE; 30 microM), on the levels of malondialdehyde (MDA), and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in human erythrocytes in vitro. Erythrocytes were incubated under various treatment conditions (malathion alone, vitamins alone, or malathion plus vitamin) at 37 degrees C for 60 min, and the levels of MDA, and SOD, CAT and GPx activities, were determined. Treatment with malathion alone increased the levels of MDA and decreased SOD, CAT, and GPx activities in erythrocytes (P < 0.05). There were no statistical differences among VC-treated, VE-treated, or VC + VE-treated erythrocyes, as compared with nontreated control cells. Treatment of cells with malathion + VC, malathion + VE, or a combination of all three agents prevented malathion-induced changes in antioxidant enzyme activity and lipid peroxidation. However, this effect was seen only at low concentrations of malathion (25 and 75 microM), and the combination of VC + VE had a more protective effect than VC or VE alone. These results indicated that the presence of vitamins at concentrations that are similar to the levels found in plasma have no effect on malathion-induced toxicity in erythrocytes at a concentration of malathion (200 microM) that is typically used in pesticides.     

Plasma phthalate and bisphenol a levels and oxidant-antioxidant status in autistic children

Phthalates and bisphenol A (BPA) are endocrine disruting chemicals (EDCs) that are suggested to exert neurotoxic effects. This study aimed to determine plasma phthalates and BPA levels along with oxidant/antioxidant status in autistic children [n = 51; including 12 children were diagnosed with “Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS)]. Plasma levels of BPA, di (2-ethylhexyl)-phthalate (DEHP) and its main metabolite mono (2-ethylhexyl)-phthalate (MEHP); thiobarbituric acid reactive substance (TBARS) and carbonyl groups; erythrocyte glutathione peroxidase (GPx1), thioredoxin reductase (TrxR), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) activities and glutathione (GSH) and selenium levels were measured. Plasma BPA levels of children with PDD-NOS were significantly higher than both classic autistic children and controls (n = 50). Carbonyl, selenium concentrations and GPx1, SOD and GR activities were higher (p < 0.05); CAT activity was markedly lower in study group. BPA exposure might be associated with PDD-NOS. Intracellular imbalance between oxidant and antioxidant status might facilitate its neurotoxicity.     

Protective effect of Zingiber officinale roscoe against anticancer drug doxorubicin-induced acute nephrotoxicity

Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by a commonly used anticancer antibiotic doxorubicin (DXN). The nephroprotective effect of aqueous ethanol extract of Zingiber officinale (200 and 400mg/kg, p.o) was evaluated against doxorubicin-induced (15mg/kg, i.p) acute renal damage in rat. Serum urea and creatinine levels were evaluated as the markers of renal failure. Renal antioxidant status such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were determined. Level of lipid peroxidation as equivalents of malondialdehyde (MDA), and glutathione-S-transferase (GST) activity were determined in the kidneys. Serum urea and creatinine levels were reduced in the Z. officinale (200 and 400mg/kg, p.o) plus DXN treated groups. The renal antioxidant enzymes activities such as SOD, CAT GPx, levels of GSH and GST activity were restored and that of MDA declined significantly (p<0.001) in the Z. officinale (400mg/kg) plus DXN treated group. The nephroprotection is mediated by preventing the DXN-induced decline of renal antioxidant status, and also by increasing the activity of GST.     

Antioxidant intervention compensates oxidative stress in blood of subjects exposed to emissions from a coal electric-power plant in South Brazil

In the process of energy generation, particulate matter (PM) emissions derived from coal combustion expose humans to serious occupational diseases, which are associated with overgeneration of reactive oxygen species (ROS). The purpose of the present study is to better understand the relations between PM exposure derived from a coal electric-power plant and the oxidative damage in subjects (n=20 each group) directly (working at the burning area) or indirectly (working at the office or living in the vicinity of the electric-power plant=group of residents) exposed to airborne contamination, before and after daily supplementation with vitamins C (500mg) and E (800mg) during six months, which were compared to non-exposed subjects (control group). Several biomarkers of oxidative stress were examined such as levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), protein thiols (PT) and vitamin E in plasma, levels of reduced glutathione (GSH) in whole blood, and of activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) in red cells. Before supplementation, TBARS and PC levels were significantly increased, levels of GSH and vitamin E were decreased, while the activities of SOD and CAT were increased in workers groups and GST were increased in all groups in compared to controls. After the antioxidant supplementation essentially all these biomarkers were normalized to control levels. The antioxidant intervention was able to confer a protective effect of vitamins C and E against the oxidative insult associated with airborne contamination derived from coal burning of an electric-power plant.     

The protective effect of flavonol quercetin against ultraviolet a induced oxidative stress in rats

Ultraviolet A (UVA) light exposed cells can induce the production of reactive oxygen species (ROS) which can damage the cellular elements. Antioxidants can interfere with the production of ROS. In this study, malondialdehyde (MDA), reduced glutathione (GSH), glutathione reductase (GSSGR), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels were measured in the liver of rats exposed to UVA light in various doses. The effects of quercetin were determined as antioxidant on those parameters. Rats were divided into three groups as control, ultraviolet (UV), and ultraviolet+quercetin (UV+Q). UV and UV+Q group rats were irradiated 4 h per day with UVA light (1.25 mW/cm(2)) during periods of 0,3,6,9 days. Thus, on days 0,3,6 and 9, the rats have received 0,54,108,162 W/cm(2) light, respectively. Quercetin (50 mg/kg body wt.) was administered intraperitoneally before each irradiation period in the UV+Q group rats. MDA level in the UV group increased significantly on day-9 when compared to the control group (P<0.05). The MDA levels in the UV+Q group decreased significantly on day-6 and 9 in comparison with the UV group (P<0.05, P<0.001, respectively). GSH levels in all groups were not significantly different. GSSGR and GPx activities in the UV group were significantly lower on day-6 and 9 than in the control group (P<0.001). On all days these enzyme activities in the UV+Q group were significantly higher than in the UV group and higher than in the control group (P<0.001). SOD and CAT activities in the UV group decreased significantly on day-3, 6, and 9 in comparison with the control group (P<0.001). These enzyme activities also increased significantly in the UV+Q group on all days when compared to the UV group (P<0.001). This study demonstrated that the exposure of rats to UVA led to oxidative stress as reflected by increased MDA levels and reduced enzymic antioxidant levels, quercetin may be useful by reducing or preventing photobiologic damage.     

Changes in antioxidant defense systems induced by thiram in V79 Chinese hamster fibroblasts.

The role of antioxidant defence systems in protection against oxidative damage of lipids and proteins induced by fungicide thiram during in vitro exposure was investigated in cultured Chinese hamster V79 cells with normal, depleted, and elevated glutathione (GSH) levels. We analyzed the catalytic activities of superoxide dismutases (SOD1 and SOD2), Se-dependent and Se-independent glutathione peroxidases (GSH-Px), glutathione reductase (GR), and catalase (CAT), as well as total glutathione/glutathione disulfide ratio (GSH(total)/GSSG). Thiram treatment resulted in an increase in activities of SOD1, Se-dependent GSH-Px, and GR at the highest tested dose (150 microM). On the contrary, inhibition of CAT and Se-independent GSH-Px activities, and no significant changes in the level of SOD2 activity was observed at any tested doses (100-150 microM). GSH(total)/GSSG ratio in the 100 microM thiram treated cells was not significantly changed comparing to the control, despite significant decrease of GSH total (50%). In 150 microM thiram treated cells the ratio falls to 43% of control value. Pretreatment with l-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, significantly enhanced decrease in CAT and Se-independent GSH-Px activities, as well as GSH(total)/GSSG ratio, and reduced Se-dependent GSH-Px activity, following exposure to thiram. Simultaneously, L-BSO pretreatment enhanced increase in SOD1 activity, and had no effect on SOD2, following thiram exposure. Pretreatment with N-acetyl cysteine (NAC), a GSH precursor, prevented enzymatic changes in CAT, Se-dependent GSH-Px, GR, SOD1 activities, and significantly decreased SOD2 activity following exposure to thiram. GSH(total)/GSSG ratio was restored to the control value. This study suggests that following the changes in antioxidant defense systems thiram can act through the production of free radicals.     

Effect of chronic exposure to simazine on oxidative stress and antioxidant response in common carp (Cyprinus carpio L.)

We investigated the chronic effect of simazine, an s-triazine herbicide commonly present in aquatic environments, on the antioxidant system and oxidative stress indices in common carp (Cyprinus carpio L.). Fish were exposed to sub-lethal concentrations of 0.06 μg l(-1) (environmental concentration in Czech rivers), 2 mg l(-1), and 4 mg l(-1) for 14, 28 and 60 days. Indices of oxidative stress [reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS)], and antioxidant parameters [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH)] in fish brain, gill, muscle, liver, and intestine were measured. Chronic exposure to simazine showed the impact of the increased production of ROS leading to oxidative damage to lipids, proteins, and inhibition of antioxidant capacity. Activity of the antioxidant enzymes SOD, CAT, GPx and GSH in groups with high concentrations (2 mg l(-1), 4 mg l(-1)) increased at 14 and 28 days, but decreased after 60 days exposure (p<0.01) as compared with the control group. Changes in enzyme activity were mainly in the liver, but also in gills and brain. Prolonged exposure to simazine resulted in excess ROS formation finally resulting in oxidative damage to cell lipids and proteins and also inhibited antioxidant capacities in common carp tissue.     

Brain and lungs of rats are differently affected by cigarette smoke exposure: Antioxidant effect of an organoselenium compound

Cigarette smoke exposure has been associated with oxidative stress in several organs. Antioxidant effect of diphenyl diselenide (PhSe)₂, an organoselenium compound, on oxidative damage induced by sub-chronic cigarette smoke exposure in brain and lungs of rats was investigated. Animals were exposed 5 times/week to one, two, three and four cigarettes for exposure periods of 15 min during the first, second, third and fourth weeks. Reactive species (RS) levels, enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol (NPSH) levels) were examined in brain and lungs of rats. An increase in RS levels induced by cigarette smoke in both tissues of rats was demonstrated. Cigarette smoke altered enzymatic antioxidant defenses (GST, CAT and SOD activities) in both tissues, and reduced the non-enzymatic antioxidant defenses in lungs. (PhSe)₂ (0.5 mg/kg/day, 5 times/week) restored RS levels and antioxidant defenses in brain of rats exposed to cigarette smoke. (PhSe)₂ treatment increased NPSH levels, GST and GR activities per se in lungs of rats. In conclusion, sub-chronic exposure to cigarette smoke caused alterations in antioxidant defense system and a tissue-specific oxidative stress in brain and lungs of rats. (PhSe)₂ restored antioxidant defenses in lungs and brain of rats.     

Evaluation of protective effect of rutin on lead acetate-induced testicular toxicity in Wistar rats

In this study, the effect of rutin (RT) was investigated on lead-induced testis tissue damage in rats. Oral administration of rutin (50?mg/kg) effectively inhibited the levels of marker enzymes and antioxidant enzymes as compared with lead acetate-treated group. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and histopathological changes of testes were investigated. Lead acetate decreased the levels of SOD, CAT, GPx, and GST compared with the control group. Light microscopic analyses revealed that lead acetate induced several histopathological changes in testis tissue. In the RT-treated group, there were statistically significantly decreases in antioxidant enzyme activities and pathological changes in the tissue. The results suggest that RT possesses significant potential in reduced lead acetate-induced testicular toxicity.     

Cytotoxic effects of zearalenone and its metabolites and antioxidant cell defense in CHO-K1 cells

Zearalenone (ZEA) and its metabolites (α-zearalenol; α-ZOL, β-zearalenol; β-ZOL) are secondary metabolites of Fusarium fungi that produce cell injury. The present study explores mycotoxin-induced cell damage and cellular protection mechanisms in CHO-K1 cells. Cytotoxicity has been determined by reactive oxygen species (ROS) production and DNA damage. ROS production was determined using the fluorescein assay and DNA strand breakage by comet assay. Intracellular protection systems were glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). The results demonstrated that all mycotoxins increased the ROS levels up to 5.3-fold the control levels in CHO-K1 cells. Zearalenone metabolites, but not ZEA, increased DNA damage 43% (α-ZOL) and 28% (β-ZOL) compared to control cells. The GSH levels decreased from 18% to 36%. The GPx and SOD activities respectively increased from 26% to 62% and from 23% to 69% in CHO-K1 cells, whereas CAT activity decreased from 14% to 52%. In addition, intracellular ROS production was induced by ZEA and its metabolites. The endogenous antioxidant system components GSH, GPx and SOD were activated against ZEA and its metabolites. These antioxidant system components thus could contribute to decrease cell injury by ZEA and its metabolites.