Oxidative damage induced in hearts, kidneys and spleens of mice by landfill leachate

The effects of the Xingou landfill leachate on levels of thiobarbituric acid reactive substances (TBARS) and the activities of Cu, Zn-superoxide dismutase (Cu, Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx) and catalase (CAT) were investigated in hearts, kidneys and spleens of Kunming albino mice of both sexes. Exposure to leachate caused significant increases of TBARS levels in the organs tested from mice of both sexes. For hearts, Cu, Zn-SOD, Se-dependent GPx and CAT activities were significantly increased at high concentrations for male mice, but the activities of these antioxidant enzymes were significantly increased at low concentration and decreased at high concentrations for female mice. For kidneys, Cu, Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations for male mice, but the activities were significantly increased at low concentrations and the ratio of increase was reduced with the increasing of concentration for female mice; CAT activities remained unchanged for male mice and were significantly increased at all concentrations tested for female mice. For spleens, Cu, Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations for male mice, but the activities were significantly increased at low concentrations and decreased at high concentrations for female mice; CAT activities remained unchanged for male mice and were significantly increased at high concentrations for female mice. The results suggest that leachate exposure can cause oxidative damage on hearts, kidneys and spleens of mice, and there were sex difference and organ difference in the response of antioxidant status.     

Cypermethrin has the potential to induce hepatic oxidative stress, DNA damage and apoptosis in adult zebrafish (Danio rerio)

Cypermethrin (CYP), a widely used Type II pyrethroid pesticide, is one of the most common contaminants in the freshwater aquatic system. We studied the effects of CYP exposure on the induction of hepatic oxidative stress, DNA damage and the alteration of gene expression related to apoptosis in adult zebrafish. Hepatic mRNA levels for the genes encoding antioxidant proteins, such as Cu/Zn-Sod, Mn-Sod, Cat, and Gpx, were significantly upregulated when zebrafish were exposed to various concentrations of CYP for 4 or 8 days. In addition, the main genes related to fatty acid β-oxidation and the mitochondrial genes related to respiration and ATP synthesis were also significantly upregulated after exposure to high concentrations (1 and 3 μg L⁻¹) of CYP for 4 or 8 days. Moreover, in a comet assay of zebrafish hepatocytes, tail DNA, tail length, tail moment and Olive tail moment increased in a concentration-dependent manner. The significant induction (p < 0.01) of all four parameters observed with CYP concentrations of 0.3 μg L⁻¹ or higher suggests that heavy DNA damage was induced even at low levels. Furthermore, several apoptosis- related genes, such as p53, Apaf1 and Cas3, were significantly upregulated after CYP exposure, and Bcl2/Bax expression ratio decreased, especially in groups treated with 1 and 3 μg L⁻¹ CYP for 8 days. Taken together, our results suggested that CYP has the potential to induce hepatic oxidative stress, DNA damage and apoptosis in zebrafish. This information will be helpful in fully understanding the mechanism of aquatic toxicology induced by CYP in fish.     

Oxidative stress, endothelial dysfunction and inflammatory response in rat heart to NO₂ inhalation exposure

Epidemiological studies suggest that NO₂ inhalation is associated with adverse effects on heart-related health, however, existing experimental data lack relevant evidences. In this study, a role for oxidative stress, endothelial dysfunction and inflammatory responses in the heart of rats treated with different concentrations of NO₂ (0, 5, 10 and 20 mg m⁻³) was investigated. Mild heart pathology occurred after 7-d exposure (6 h d⁻¹). Marked oxidative stress were induced as evaluated by reduction/induction of antioxidants (Cu/Zn-SOD, Mn-SOD and GPx) activity and increasing formation of MDA and PCO. Also, mRNA and protein biomarkers of vasoconstriction (ET-1, eNOS) and inflammation (TNF-α, IL-1β and ICAM-1) were up-regulated, and p53 mRNA expression, bax/bcl-2 ratio and the mean number of TUNEL-positive myocytes were increased as well. All the results implicate that NO₂ exerted injuries to mammals’ heart, and the damage mechanisms were possibly associated with oxidative stress, endothelial dysfunction and inflammation.     

Heavy metal concentrations in molluscs from the Atlantic coast of southern Spain

Trace metals were determined in the two most abundant species of bivalve molluscs along the Atlantic coast of southern Spain (Donax trunculus and Chamelea gallina) and in the sediments where they live. The results show that the area near the mouth of the Huelva estuary is where the highest metal concentrations are found in sediments and in the two bivalve species. This is not surprising, considering that the Huelva estuary is the mouth of the Tinto and Odiel rivers, which have one of the highest levels of metal pollution of all the rivers of Europe. The two species of bivalves have different amounts of metals in their tissues. The concentrations of Cr, Cu, Pb, Zn, As and Hg in D. trunculus were significantly higher (p < 0.05) than in C. gallina; however, C. gallina contained more Ni and Cd. In both species the most abundant elements were Cu and Zn, while Hg showed the lowest values. There is a significant correlation (p < 0.05) for concentrations of Cu, Pb, Zn and Hg in D. trunculus and C. gallina relative to their concentrations in surface sediments.     

Effects of benzo[a]pyrene as an environmental pollutant and two natural antioxidants on biomarkers of reproductive dysfunction in male rats

Benzo[a]pyrene (B[a]P) is an environmental toxicant and endocrine disruptor. Therefore, the aim of the present study was to investigate the toxicity of B[a]P in testis of rats and also to study the role of silymarin and thymoquinone (TQ) as natural antioxidants in the alleviation of such toxicity. Data of the present study showed that levels of testosterone, estrogen and progesterone were significantly decreased after treatment of rats with B[a]P. In addition, B[a]P caused downregulation of the expressions of steroidogenic enzymes including CYP17A1 and CP19A1, and decreased the activity of 17-β hydroxysteroid dehydrogenase (17β-HSD). Moreover, B[a]P decreased the activities of antioxidant enzymes including catalase (CAT), glutathione peroxidase (GP_X) and superoxide dismutase (SOD), and significantly increased free radicals levels in testis of male rats. However, pretreatment of rats with silymarin prior to administration of B[a]P was found to restore the level of free radicals, antioxidant status, and activities of steroidogenic enzymes to their normal levels in testicular tissues. Moreover, histopathological finding showed that silymarin recovered the abnormalities occurred in tubules caused by B[a] P in testis of rats. On the other hand, TQ showed pro-oxidant effects and did not ameliorate the toxic effects of B[a] P on the testicular tissue since it decreased antioxidant enzymes activities and inhibited the protein expression of CYP11A1 and CYP21A2 compared to control rats. Moreover, TQ decreased the levels of testosterone, estrogen, and progesterone either in the presence or absence of B[a]P. It is concluded that B[a]P decreased testosterone levels, inhibited antioxidant enzymes activities, caused downregulation of CYP isozymes involved in steroidogenesis, and increased free radical levels in testis. Moreover, silymarin was more effective than TQ in restoring organism health and alleviating the deleterious effects caused by B[a]P in the testis of rats. Due to its negative impact, it is highly recommended to limit the use of TQ as a dietary supplement since millions of people in the Middle East are using it to improve their health.

     

柠檬酸对褐土中DTPA提取态铜、镉含量及对紫花苜蓿吸收铜、镉的影响

为了阐述有机酸对土壤中重金属生物有效性的影响,通过盆栽实验,研究了Cu、Cd复合污染下柠檬酸对褐土中二乙基三胺五乙酸(DTPA)提取态铜和镉含量的影响,并探讨了柠檬酸对植物吸收铜、镉的影响。结果表明,土壤中DT-PA-Cu含量随柠檬酸添加量的增加而减小,添加高浓度铜(Cu 1 000)处理中,DTPA-Cu含量减小更明显。在添加低铜浓度(Cu600)处理下,柠檬酸添加量为2和12 mmol/kg时,土壤DTPA-Cu含量随土壤镉含量的增加而增加,而柠檬酸含量为5mmol/kg时,DTPA-Cu含量在低镉处理(Cd 1)时含量最低。紫花苜蓿中铜含量随柠檬酸添加量的增加明显降低。土壤中DTPA-Cd含量随柠檬酸添加量的增加而减小,且随铜添加量的增加而降低。紫花苜蓿中的镉含量随柠檬酸添加量的增加先增加后减小;在相同柠檬酸添加量处理时,紫花苜蓿中镉的含量随镉含量的增加而增加;在低镉处理下,铜的加入对较低柠檬酸浓度时紫花苜蓿镉含量影响不明显,但柠檬酸浓度为12 mmol/kg时,紫花苜蓿中镉含量随铜添加量的增加而明显增加。     

Impacts of Antioxidants on Hydroxyl Radical Production from Individual and Mixed Transition Metals in a Surrogate Lung Fluid

Inhalation of ambient particulate matter causes morbidity and mortality in humans. One hypothesized mechanism of toxicity is the particle-induced formation of reactive oxygen species (ROS) - including the highly damaging hydroxyl radical ((·)OH) - followed by inflammation and a variety of diseases. While past studies have found correlations between ROS formation and a variety of metals, there are no quantitative measurements of (·)OH formation from transition metals at concentrations relevant to 24-hour ambient particulate exposure. This research reports specific and quantitative measurements of (·)OH formation from 10 individual transition metals (and several mixtures) in a cell-free surrogate lung fluid (SLF) with four antioxidants: ascorbate, citrate, glutathione, and uric acid. We find that Fe and Cu can produce (·)OH under all antioxidant conditions as long as ascorbate is present and that mixtures of the two metals synergistically increase (·)OH production. Manganese and vanadium can also produce (·)OH under some conditions, but given that their ambient levels are typically very low, these metals are not likely to chemically produce significant levels of (·)OH in the lung fluid. Cobalt, chromium, nickel, zinc, lead, and cadmium do not produce (·)OH under any of our experimental conditions. The antioxidant composition of our SLF significantly affects (·)OH production from Fe and Cu: ascorbate is required for (·)OH formation, citrate increases (·)OH production from Fe, and both citrate and glutathione suppress (·)OH production from Cu. MINTEQ ligand speciation modeling indicates that citrate and glutathione affect (·)OH production by changing metal speciation, altering the reactivity of the metals. In the most realistic SLF (i.e., with all four antioxidants), Fe generates approximately six times more (·)OH than does the equivalent amount of Cu. Since levels of soluble Fe in PM are typically higher than those of Cu, our results suggest that Fe dominates the chemical generation of (·)OH from deposited particles in the lungs.     

The copper tolerance strategies and the role of antioxidative enzymes in three plant species grown on copper mine

This study was undertaken to identify the strategies and the status of antioxidant enzyme activities involved in three plant species tolerance against Cu-toxicity in copper mine. The following methods were used for evaluations in three wild type species; Datura stramonium, Malva sylvestris and Chenopodium ambrosioides. The level of chlorophyll and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) by spectrometry, malondialdehyde (MDA) and dityrosine by HPLC and the levels of Cu in tissues and soils by atomic absorption spectrometry (AAS).

Analysis showed that total and available copper were at toxic levels for plants growing on contaminated soil (zone 1). However, there were not any visual and conspicuous symptoms of Cu toxicity in plant species. Among three species, excess copper was transferred only into the D. stramonium and C. ambrosioides tissues. The C. ambrosioides accumulated Cu in roots and then in leaves, in which the leaves chloroplasts stored Cu around two times of vacuoles. In D. stramonium most of Cu was accumulated in leaves in which the storage rate in vacuoles and chloroplasts were 42% and 8%, respectively. In zone 1, the chlorophyll levels increased significantly in leaves of C. ambrosioides with respect to the same plant growing on uncontaminated soil (zone 2). There was insignificant decrease in chlorophyll content of D. stramonium leaves, collected from zone 1 with respect to zone 2. The D. stramonium and C. ambrosioides in zone 1, both revealed significant increase in their tissues antioxidant enzyme activities in comparison with the same samples of zone 2. There was significant elevation in oxidative damage biomarkers; MDA and dityrosine, when the aerial parts of D. stramonium in zone 1 were compared with the same parts of zone 2.

We concluded that there were different tolerance strategies in studied plant species that protected them against copper toxicity. In M. sylvestris, exclusion of Cu from the roots or its stabilization in the soil restricted Cu toxicity effects. On the other hand D. stramonium and C. ambrosioides, elevated their antioxidative enzyme activities in response to cu-toxicity. In addition, the species D. stramonium accumulated excess of Cu in leaves vacuoles.     

Antioxidant and metabolism responses to polyphenol stress in cyanobacterium Microcystis aeruginosa

Three common polyphenol compounds Gallic Acid (GA), Pyrogallic Acid (PA) and Catechol (CA) are known to have allelochemical-exhibiting inhibitory effects on the growth of the cyanobacterium Microcystis aeruginosa (M. aeruginosa). Metabolism and antioxidant responses in M. aeruginosa were investigated to elucidate the mechanism by which the three polyphenols inhibit algal growth. The inhibition effects of polyphenols were in the order of CA > PA > GA. The GA and CA exposures increased protein contents, superoxide dismutase (SOD) activity, catalase (CAT) activity and soluble sugar, especially for exposure to GA of 25 mg L^?1. Soluble sugar content increased significantly especially when exposed to CA for 72 h. When exposed to PA, protein content, and SOD and CAT activities initially increased but over longer treatment time the activities decreased, in contrast to sugar content. Our results suggest that PA exposure for longer periods of time may inhibit catabolism action, while CA exposure could induce more oxide stress than GA or PA. The overall study showed that polyphenol-induced oxidative damage might be responsible for polyphenol inhibition on M. aeruginosa growth. The increases in cellular antioxidant enzymes and soluble sugar may have been to counteract the oxidative stress.     

Ecotoxicological effects on the earthworm Eisenia fetida following exposure to soil contaminated with imidacloprid

Imidacloprid, a neonicotinoid insecticide, has been used widely in agriculture worldwide. The adverse effects of imidacloprid on exposed biota have brought it increasing attention. However, knowledge about the effects of imidacloprid on antioxidant defense systems and digestive systems in the earthworm is vague and not comprehensive. In the present study, the changes in the activity of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), cellulase, reactive oxygen species (ROS), and malondialdehyde (MDA) in the earthworm Eisenia fetida exposed to artificial soil treated with imidacloprid were examined systematically. The results showed that the activity of these biomarkers was closely related to the dose and duration of the exposure to imidacloprid. The activity of SOD was stimulated significantly at doses of 0.66 and 2 mg kg^?1 imidacloprid but markedly inhibited at a dose of 4 mg kg^?1 imidacloprid with prolonged exposure. The activities of CAT and POD increased irregularly at 0.2–4 mg kg^?1 imidacloprid over different exposure times. The level of ROS at a dose of 2 or 4 mg kg^?1 imidacloprid was significantly increased over the entire exposure period. When the concentration of imidacloprid was above 0.66 mg kg^?1, the balance of the activity of the antioxidant enzymes and ROS level was interrupted. The activity of cellulase decreased significantly with prolonged exposure. At the stress of 4 mg kg^?1 imidacloprid, the content of MDA was significantly increased with increasing exposure time. The results of the present study suggest that imidacloprid has a potentially harmful effect on E. fetida and may be helpful for assessment of the risk of imidacloprid to the soil ecosystem environment. However, to obtain more comprehensive toxicity data, it is necessary to investigate the effects of imidacloprid on earthworm using native soils in the future work.     

Damage to DNA caused by UV-B radiation in the desert cyanobacterium Scytonema javanicum and the effects of exogenous chemicals on the process

Radiation with UV-B increased the damage to DNA in Scytonema javanicum, a desert-dwelling soil microorganism, and the level of damage varied with the intensity of UV-B radiation and duration of exposure. Production of reactive oxygen species (ROS) also increased because of the radiation. Different exogenous chemicals (ascorbate acid, ASC; N-acetylcysteine, NAC; glyphosate, GPS; and 2-methyl-4-chlorophenoxyacetic acid, MCPA-Na) differed in their effect on the extent of DNA damage and ROS production: whereas NAC and ASC protected the DNA from damage and resulted in reduced ROS production, the herbicides (GPS and MCPA-Na) increased the extent of damage, lowered the rate of photosynthesis, and differed in their effect on ROS production. The chemicals probably have different mechanisms to exercise their effects: NAC and ASC probably function as antioxidant agents or as precursors of other antioxidant molecules that protect the DNA and photosynthetic apparatus directly from the ROS produced as a result of UV-B radiation, and GPS and MCPA-Na probably disrupt the normal metabolism in S. javanicum to induce the leaking of ROS into the photosynthetic electron transfer pathway following UV-B radiation, and thereby damage the DNA. Such mechanisms have serious implications for the use of environment-friendly herbicides, which, because they can destroy DNA, may prove harmful to soil microorganisms.     

Inhibition of the antioxidant activity of catalase and superoxide dismutase from Fusarium verticillioides exposed to a Jacquinia macrocarpa antifungal fraction

The aim of this study was to investigate the in vitro effect of an antifungal fraction obtained from Jacquinia macrocarpa plant (JmAF) in the generation of reactive oxygen species (ROS) and the activity of the catalase (CAT) and superoxide dismutase (SOD) enzymes from Fusarium verticillioides, as well as their influence in the viability of the fungus spores. The compounds present in the JmAF were determined by gas chromatography/quadrupole time-of-flight mass spectrometry (GC/QTOF-MS). The effect of the exposition to JmAF on the generation of ROS, as well as in the CAT and SOD activities in F. verticillioides, was determined. The main compounds detected were γ-sitosterol, stephamiersine, betulinol and oleic acid. JmAF showed very high ability in inhibiting the spore viability of F. verticillioides, and their capacity to cause oxidative stress by induction of ROS production. JmAF induced the highest ROS concentration and also inhibited CAT and SOD activities. The results obtained in this study indicate that JmAF is worthy of being considered for the fight against phytopathogenic fungi.     

Atrazine promotes biochemical changes and DNA damage in a Neotropical fish species

The effects of Atrazine, an herbicide used worldwide and considered as a potential contaminant in aquatic environments, were assessed on the Neotropical fish Prochilodus lineatus acutely (24 and 48 h) exposed to 2 or 10 μg L⁻¹ of atrazine by using a set of biochemical and genetic biomarkers. The following parameters were measured in the liver: activity of the biotransformation enzymes ethoxyresorufin-O-deethylase (EROD) and glutathione S transferase (GST), antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), content of reduced glutathione (GSH), generation of reactive oxygen species (ROS) and occurrence of lipid peroxidation (LPO); in brain and muscle the activity of acetylcholinesterase (AChE) and DNA damage (comet assay) on erythrocytes, gills and liver cells. A general decreasing trend on the biotransformation and antioxidant enzymes was observed in the liver of P. lineatus exposed to atrazine; except for GR, all the other antioxidant enzymes (SOD, CAT and GPx) and biotransformation enzymes (EROD and GST) showed inhibited activity. Changes in muscle or brain AChE were not detected. DNA damage was observed in the different cell types of fish exposed to the herbicide, and it was probably not from oxidative origin, since no increase in ROS generation and LPO was detected in the liver. These results show that atrazine behaves as enzyme inhibitor, impairing hepatic metabolism, and produces genotoxic damage to different cell types of P. lineatus.     

Oxidative stress and lipid peroxidation in the earthworm Eisenia fetida induced by low doses of fomesafen

Formesafen is a diphenyl ether herbicide that has adverse effects on non-target animals. However, knowledge about the effect of fomesafen on the antioxidant defense system in earthworms is vague. Thus, it is essential to investigate the effects of fomesafen on the antioxidant defense system in earthworms as a precautionary method. In the present study, earthworms (Eisenia fetida) were exposed to artificial soil treated with a range of concentrations of fomesafen (0, 10, 100, and 500 μg kg^?1) and were collected on the 3rd, 7th, 14th, 21st, and 28th days of exposure. Subsequently, the antioxidant enzyme activities (superoxide dismutase (SOD); catalase (CAT); and guaiacol peroxidase (POD)), reactive oxygen species (ROS) level, and malondialdehyde (MDA) content due to fomesafen treatment were examined in earthworms. Compared with the control, the SOD activity increased on the third and seventh days but decreased on the 14th day due to treatment with 100 and 500 μg kg^?1 of fomesafen. The activities of CAT and POD increased significantly on the third, seventh, and 14th days of exposure. In addition, the ROS level was significantly enhanced throughout the entire experimental period and showed a statistically dose-dependent relationship on the seventh and 14th days. The MDA content markedly increased on the seventh day of exposure; however, obvious changes were not detected at other exposure period. Low doses of fomesafen (≤500 μg kg^?1) may result in oxidative damage and lipid peroxidation in E. fetida by inducing the generation of ROS at short exposure periods (14 days). However, the adverse effects of fomesafen gradually disappear as the cooperation of antioxidant enzymes and exposure time are prolonged. This result may be helpful for further studies on the toxicological mechanisms of fomesafen to earthworms.     

Protective effect of silymarin on erythrocyte haemolysate against benzo(a)pyrene and exogenous reactive oxygen species (H2O2) induced oxidative stress

The present study was carried out to evaluate the in vitro antioxidant properties and protective effects of silymarin (milk thistle) in human erythrocyte haemolysates against benzo(a)pyrene [B(a)P], a potent carcinogenic chemical. Protective effect of silymarin was assessed in vitro by monitoring the antioxidant enzymes and malondialdehyde in three groups of haemolysates-(I) vehicle control (II) B(a)P incubated group and (III) B(a)P co incubated with silymarin. The effects of silymarin on lipid peroxidation (LPO) and antioxidant enzymes [superoxide dismutase; SOD, catalase; CAT, glutathione peroxidase; GPx, glutathione reductase; GR and glutathione-S-transferases; GST] were assessed on haemolysates. It was observed that specific activity of antioxidant enzymes were significantly decreased and the malondialdehyde levels were elevated when haemolysates were incubated with B(a)P. The protective effect of silymarin is elucidated by the significant reversal of the antioxidant enzymes and reduction in the levels of malondialdehyde. In addition, haemolysates were incubated with B(a)P for 45 min and the B(a)P metabolite, 3-hydroxy benzo(a)pyrene (3-OH-B(a)P) was detected using HPLC. An increased level of the metabolite was detected in group II. Whereas, when haemolysates were co-incubated with silymarin, the reactive metabolite 3-OH-B(a)P was not detectable which further confirms the protective role of silymarin. Generation of 3-OH-B(a)P in group II implicates the possibility of reactive oxygen species (O2- and H2O2) production in haemolysates during cytochrome P4501A1 (CYP1A1) mediated Phase-I-metabolism. Hence, we incubated the haemolysates with exogenous reactive oxygen species H2O2 and assessed the protective role of silymarin against H2O2. From the results of our study, it was suggested that silymarin possess substantial protective effect and free radical scavenging mechanism against environmental contaminants induced oxidative stress damages.     

Expression alterations of cytochromes P4501A1, 2E1, and 3A,and their receptors AhR and PXR caused by 1-octyl-3-methylimidazolium chloride in mouse mammary carcinoma cells

Cytochrome P450s (CYPs) play a key role in the metabolism of a wide range of environmental xenobiotics and endogenous compounds. The expression and activity levels of CYPs can be elevated by a process of induction involving the activation of nuclear receptors. The effects of the ionic liquid 1-octyl-3-methylimidazolium chloride ([C₈mim][Cl]) on the expression of cytochrome P450 members, including CYP1A1, CYP2E1, and CYP3A, as well as on aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) in mouse mammary carcinoma cells (EMT6) were investigated by using quantitative real-time PCR in the present study. The results reveal that [C₈mim][Cl]-exposure up-regulates the expressions of CYP1A1, CYP2E1, and CYP3A at mRNA level, suggesting that imidazolium-based ionic liquids can activate CYPs. Our results also suggest that [C₈mim][Cl]-mediated CYP3A induction be PXR-dependent. This result may be beneficial to evaluating the environmental toxicity of imidazolium-based ionic liquids and investigating the metabolism of imidazolium-derivative drugs.     

Cytotoxic effect of fenitrothion and lambda-cyhalothrin mixture on lipid peroxidation and antioxidant defense system in rat kidney

A mixture of pyrethroids plus organophosphates was assessed for their potential effects on lipid peroxidation, the antioxidant defense system and lactate dehydrogenase (LDH) in rat kidney in vitro. Various insecticide concentrations were incubated with kidney homogenate at 37°C for different incubation times. Treatment with fenitothion (FNT) plus lambda-cyhalothrin (LC) caused a significant induction (P < 0.05) in thiobarbituric acid reactive substances (TBARS), which might be associated to decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) activities and protein content in rat kidney. However, a significant induction of lactate dehydrogenase (LDH) activity was observed. The effect was concentration and time dependent. It can be concluded that depletion of GSH might indicate that reactive oxygen species (ROS) could be involved in the toxic effects of FNT plus LC which lead to marked perturbations in antioxidant defense system.