Hematotoxicity and blood glutathione levels after cisplatin treatment of tumor-bearing mice

The involvement of glutathione, a major cellular antioxidant, in cisplatin-mediated development of various hematological changes in mice bearing ascites Dalton lymphoma tumor was investigated. With tumor growth, glutathione levels decreased in blood but increased in tumor cells. Cisplatin treatment of tumor-bearing mice caused a decrease in glutathione levels in blood, ascites supernatant, and tumor cells. Blood hemoglobin, erythrocytes, packed cell volume and leukocytes (eosinophils, basophils, and lymphocytes) were also decreased along with the development of various morphological abnormalities in erythrocytes (microcytes, macrocytes, echinocytes, acanthocytes, etc.) after cisplatin treatment. All these hematotoxic features were noted to be increased more when buthionine sulfoximine (a specific glutathione-depleting agent) was also given prior to cisplatin treatment. However, combination treatment of cysteine (precursor for glutathione synthesis) plus cisplatin resulted in an improvement in the glutathione levels and decrease in hematological toxicities. It is noted that the glutathione levels in blood and abnormalities in erythrocytes and other hematological parameters are inversely related in cisplatin-mediated cancer chemotherapy. It is suggested that blood glutathione may play an important role in the development of cisplatin-mediated hematological toxicity in the host. This revised version was published online in July 2006 with corrections to the Cover Date.     

Comparative effects of selenite and selenite on the glutathione-related enzymes activity in pig blood platelets

The effects of inorganic selenium (Se) compounds (sodium selenite and selenate) on the activities of glutathione-related enzymes (glutathione peroxidase, glutathione-S-transferase [GST] and glutathione reductase [GR]) in pig blood platelets were investigated in vitro. GST activity in blood platelets treated with 10⁻⁴ M of selenite was reduced to 50%, whereas no decrease GST activity was observed after the treatment of platelets with the same dose of selenate. In platelets incubated with physiological doses (10⁻⁷, and 10⁻⁶ M) of Se compounds, the activity of glutathione peroxidase (GSH-Px) was enhanced (about 20%). GR activity after the exposure of platelets to tested Se compounds was unaffected.     

Copper-induced changes in the growth, oxidative metabolism, and saponin production in suspension culture roots of Panax ginseng in bioreactors

Roots of Panax ginseng exposed to various concentrations of Cu (0.0, 5, 10.0, 25.0, and 50.0 μM) accumulated high amounts of Cu in a concentration-dependent and duration-dependent manner. Roots treated with 50 μM Cu resulted in 52% and 89% growth inhibition after 20 and 40 days, respectively. Saponin synthesis was stimulated at a Cu concentration between 5 and 25 μM but decreased at 50 μM Cu. Malondialdehyde content (MDA), lipoxygenase activity (LOX), superoxide ion (O₂ ^•−) accumulation, and H₂O₂ content at 5 and 10 μM Cu-treated roots were not increased but strongly increased at 50 μM Cu resulting in the oxidation of ascorbate (ASC) and glutathione (GSH) to dehydroascorbate (DHA) and glutathione disulfide (GSSG), respectively indicating a clear oxidative stress. Seven well-resolved bands of superoxide dismutase (SOD) were detected in the gel and an increase in SOD activity seemed to be mainly due to the induction of Fe-SOD 3. Five to 10 μM Cu slightly induced activity of ascorbate peroxidase (APX) and dehydroascorbate reductase (DHAR), guaiacol peroxidase (G-POD) but inhibited monodehydroascorbate reductase (MDHAR) and glutathione reductase (GR) enzyme activities. No changes in catalase (CAT) activity and in activity gel were found up to 25 μM Cu, but both G-POD and CAT activities were inhibited at 50 μM Cu. Glutathione metabolism enzymes such as γ-glutamylcysteine synthetase (γ-GCS), glutathione-S-transferase (GST), and glutathione peroxidase activities (GPx) were activated at 5 and 10 μM Cu but were strongly inhibited at 50 μM Cu due to the Cu accumulation in root tissues. The strong depletion of GSH at 50 μM Cu was associated to the strong induction of γ-glutamyltranspeptidase (γ-GGT) activity. These results indicate that plant could grow under Cu stress (5–25 μM) by modulating the antioxidant defense mechanism for combating Cu induced oxidative stress.     

Developmental Aspects of Detoxifying Enzymes in Fish (Salmo Iridaeus)

The activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione transferase and glyoxalase I have been studied during the embryologic development of rainbow trout (Salmo iridaeus) and in several other trout tissues to investigate the protective development metabolism.

A gradual increase of superoxide dismutase, catalase, glutathione reductase, glyoxalase I and glutathione transferase activities was noted throughout embryo development.

In all trout tissues investigated glutathione peroxidase was found to be extremely low compared to catalase activity. The highest activity of superoxide dismutase, glyoxalase I and glutathione reductase was found in liver followed by kidney.

No change in the number of GST subunits was noted with the transition from the embryonic to the adult stages of life according to the SDS/PAGE and HPLC analyses performed on the GSH-affinity purified fractions.     

Effect of cisplatin on mitochondrial protein, glutathione, and succinate dehydrogenase in Dalton lymphoma-bearing mice

Cisplatin treatment of tumor-bearing mice resulted a significant decrease of protein in the tissues studied (liver, kidney, and Dalton lymphoma) and also in their mitochondrial fractions. As compared to respective tissues, the protein decrease was noted to be more conspicuous in their mitochondrial fractions. Similarly, mitochondrial glutathione also decreased significantly in the tissues. However, succinate dehydrogenase activity was selectively decreased in the kidney and Dalton lymphoma cells, whereas in liver it remained almost unchanged. An increase in serum urea concentration and kidney mitochondrial lipid peroxidation was also observed after cisplatin treatment. It is suggested that the cisplatin-induced biochemical changes in mitochondria involving mitochondrial protein, glutathione, and succinate dehydrogenase could be the important potent cellular sites contributing to toxicity/cytotoxicity after cisplatin treatment. This revised version was published online in July 2006 with corrections to the Cover Date.     

Changes in apoplastic antioxidants induced by powdery mildew attack in oat genotypes with race non-specific resistance

Three oat (Avena sativa L.) lines which show differential responses to attack by the biotrophic fungal pathogen Blumeria graminis DC f. sp. avenae Marchal, which causes powdery mildew, were studied: Maldwyn shows the strongest resistance in adult plants; Selma shows greater susceptibility; while a Selma × Maldwyn hybrid, OM1387, has a similar degree of resistance to Maldwyn. Host responses to pathogen attack were complete 48 h after inoculation but largely accomplished within the first 24 h, the point when material was taken for enzyme and metabolic assays. In Maldwyn and OM1387 about 80% of attacked cells showed localized autofluorescent host-cell responses but this fell to less than 20% in Selma. A cytoplasmic marker enzyme, glucose 6-phosphate dehydrogenase, was used to determine contamination of the apoplastic extracts by cellular components. After correction for cytoplasmic contamination, up to 4% of the total foliar activities of superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase and monodehydroascorbate reductase activities were detected in the apoplast. The apoplast contained about 2% of the total foliar glutathione pool and dehydroascorbate, but not ascorbate, at values amounting to 10% of the total foliar ascorbate plus dehydroascorbate pool. Twenty-four hours after inoculation the foliar or apoplastic ascorbate pools were similar in inoculated and control leaves. Foliar catalase activity increased in both susceptible and resistant responses. Resistance correlated with increased total foliar glutathione, an increase in the ratio of reduced to oxidized glutathione and with decreased total activities of foliar ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase and monodehydroascorbate reductase. Received: 17 April 1998 / Accepted: 28 August 1998     

Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats

Using diabetes mellitus as a model of oxidative damage, this study investigated whether subacute treatment (10 mg/kg/day, intraperitoneally for 14 days) with the compound piperine would protect against diabetes-induced oxidative stress in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively) content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Piperine treatment of normal rats enhanced hepatic GSSG concentration by 100% and decreased renal GSH concentration by 35% and renal glutathione reductase activity by 25% when compared to normal controls. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with piperine reversed the diabetic effects on GSSG concentration in brain, on renal glutathione peroxidase and superoxide dismutase activities, and on cardiac glutathione reductase activity and lipid peroxidation. Piperine treatment did not reverse the effects of diabetes on hepatic GSH concentrations, lipid peroxidation, or glutathione peroxidase or catalase activities; on renal superoxide dismutase activity; or on cardiac glutathione peroxidase or catalase activities. These data indicate that subacute treatment with piperine for 14 days is only partially effective as an antioxidant therapy in diabetes.     

Cadmium and copper induction of oxidative stress and antioxidative response in tomato (<Emphasis Type="Italic">Solanum lycopersicon</Emphasis>) leaves

We compare cadmium and copper induced oxidative stress in tomato leaves and the antioxidative enzyme response during a time course of 96 h. Plants were subjected to 25 μM of CdCl₂ or CuSO₄ and malondialdehyde (MDA) level and activity of guaiacol peroxidase, superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase were determined. The results showed that there was an early increase in the MDA level and in the guaiacol peroxidase activity more pronounced with copper exposure during almost all the time course of the experiment. The activity of superoxide dismutase and catalase was induced very early after cadmium and copper treatment, reached a maximal value after 12 h and then declined but it remained always slightly higher than the control at the end of the experiment. Ascorbate peroxidase activity pathway was similar to superoxide dismutase or catalase with a maximal activity after 48 h of heavy metal exposure. Induction of glutathione reductase activity observed only under copper exposure is maintained during almost all the experimental time. The antioxidative activity developed by tomato leaves is more induced by copper treatment. This can be related to the ability of this metal to induce more than cadmium an accumulation of reactive oxygen species (ROS) at the cellular level. Decline in the antioxidative enzymes activity at the end of the experiment can be a consequence of cadmium- and copper-inducing a further ROS formation that might affect enzymes activity.     

Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice

Both Cinnamomi cassiae and Rhodiola rosea extracts are used as anti-diabetic folk medicines. Recently, increased oxidative stress was shown to play an important role in the etiology and pathogenesis of diabetes mellitus and its complications. This study was designed to examine the effects of Cinnamomi cassiae and Rhodiola rosea extracts on blood glucose, lipid peroxidation, the level of reduced glutathione and its related enzymes (glutathione reductase, glutathione S-transferase), and the activity of the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) in the liver of db/db mice. Diabetic C57BL/Ks db/db mice were used as experimental models. Mice were divided into control (n=10), Cinnamomi cassiae (200 mg/kg/day, n=10), and Rhodiola rosea (200 mg/kg/day, n=10) treated groups for 12 weeks of treatment. These type II diabetic mice were used to investigate the effects of Cinnamomi cassiae and Rhodiola rosea on blood glucose, reduced glutathione, glutathione reductase, glutathione S-transferase, glutathione peroxidase, lipid peroxidation, catalase and superoxide dismutase. Cinnamomi cassiae and Rhodiola rosea extracts significantly decreased on blood glucose, increased levels of reduced glutathione and the activities of glutathione reductase, glutathione S-transferase, glutathione peroxidase, catalase and superoxide dismutase in the liver. Extract treatment also significantly decreased lipid peroxidation. Cinnamomi cassiae and Rhodiola rosea extracts may be effective for correcting hyperglycemia and preventing diabetic complications.     

Structural and biochemical changes in mitochondria after cisplatin treatment of Dalton’s lymphoma-bearing mice

Cisplatin treatment of tumor-bearing mice and analysis of ultrastructural features of mitochondria in the kidney and Dalton’s lymphoma cells showed the appearance of more roundish mitochondria with thickened membranes. It also caused the reduction in the number and irregularity in the shape of cristae and formation of vacuoles in the mitochondria. After cisplatin treatment, decreased level of protein, succinate dehydrogenase activity, and increased level of lipid peroxidation were noted in Dalton’s lymphoma tumor cells and kidney. Cisplatin-mediated decrease in SDH activity, GSH level and an increase in LPO in the mitochondria of kidney could play an important role to produce nephrotoxicity. However, in DL cells, decrease in cellular GSH could be noteworthy than mt-GSH, along with decrease in SDH activity and increase in LPO in the cisplatin-mediated anticancer activity. These changes could play an important role to produce both the cisplatin-mediated effects i.e. anticancer activity and nephrotoxicity. Cisplatin-induced biochemical and ultrastructural changes in mitochondria after cisplatin treatment should be an important factor in the development of biochemical injury in mitochondria and affecting the overall metabolism in the cells. The findings from the present studies indicate multilevel effect of cisplatin in the cells and do support the earlier view that mitochondria could be a critical target in cisplatin-mediated anticancer activity and toxicity in the hosts.     

Involvement of Lipid Peroxidation in Water Stress-Promoted Senescence of Detached Rice Leaves

Role of lipid peroxidation and antioxidative enzymes (catalase, peroxidase, superoxide dismutase, ascorbate peroxidase and glutathione reductase) in water stress-promoted senescence of detached rice leaves was investigated. The senescence was followed by measuring the decrease in protein content. Increased lipid peroxidation was closely correlated with senescence in water stressed leaves. Decrease in superoxide dismutase activity was evident 8 h after beginning of water stress. However, decreased catalase, peroxidase, and ascorbate peroxidase activity was observed only when senescence was observed. Glutathione reductase was not affected by water stress. Free radical scavengers retarded water stress-enhanced senescence.     

Tellurium-induced dose-dependent impairment of antioxidant status: differential effects in cerebrum,cerebellum, and brainstem of mice

The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8, and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-S-transferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However, the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts of the mice brain.     

Methyl jasmonate and salicylic acid elicitation induces ginsenosides accumulation, enzymatic and non-enzymatic antioxidant in suspension culture Panax ginseng roots in bioreactors

The effects of methyl jasmonate (MJ) and salicylic acid (SA) on changes of the activities of major antioxidant enzymes, superoxide anion accumulation (O₂ ⁻), ascorbate, total glutathione (TG), malondialdehyde (MDA) content and ginsenoside accumulation were investigated in ginseng roots (Panax ginseng L.) in 4 l (working volume) air lift bioreactors. Single treatment of 200 μM MJ and SA to P. ginseng roots enhanced ginsenoside accumulation compared to the control and harvested 3, 5, 7 and 9 days after treatment. MJ and SA treatment induced an oxidative stress in P. ginseng roots, as shown by an increase in lipid peroxidation due to rise in O₂ ⁻ accumulation. Activity of superoxide dismutase (SOD) was inhibited in MJ-treated roots, while the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), SOD, guaiacol peroxidase (G-POD), glutathione peroxidase (GPx) and glutathione reductase (GR) were induced in SA-treated roots. A strong decrease in the activity of catalase (CAT) was obtained in both MJ- and SA-treated roots. Activities of ascorbate peroxidase (APX) and glutathione S transferase (GST) were higher in MJ than SA while the contents of reduced ascorbate (ASC), redox state (ASC/(ASC+DHA)) and TG were higher in SA- than MJ-treated roots while oxidized ascorbate (DHA) decreased in both cases. The result of these analyses suggests that roots are better protected against the O₂ ⁻ stress, thus mitigating MJ and SA stress. The information obtained in this work is useful for efficient large-scale production of ginsenoside by plant-root cultures.     

Prevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by S-allylcysteine

Chemopreventive effect of S-allylcysteine (constituent of garlic) on N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis was evaluated in Wistar rats. Significantly decreased lipid peroxidation products (thiobarbituric acid reactive substances-TBARS and lipid hydroperoxides) with increased level of reduced glutathione, increased activities of glutathione S-transferase, and glutathione peroxidase were observed in liver of NDEA-treated rats when compared with control rats. The activities of superoxide dismutase and catalase were significantly decreased in tumor tissue when compared with control. Administration of S-allylcysteine (SAC) showed the inhibition of tumor incidence, modulated the lipid peroxidation, and increased the reduced glutathione, glutathione-dependent enzymes, superoxide dismutase, and catalase in NDEA-induced carcinogenesis. From our results, we speculate that S-allylcysteine mediates its chemopreventive effects by modulating lipid peroxidation, GST stimulation, and by increasing the antioxidants. Hence SAC prevents cells from loss of oxidative capacity in NDEA-induced hepatocarcinogenesis.     

Role of antioxidative system during the development and senescence of cucumber fruit

The oxidative processes and antioxidative system in cucumber (Cucumis sativus L.) fruit were determined during development and senescence. Four distinct developmental stages could be delineated during fruit maturation: immature (3–8 d after anthesis, DAA), mature (9–16 DAA), breaker (17–22 DAA), and yellow (35–40 DAA). The electrolyte leakage, malondialdehyde content, superoxide anion production rate, and hydrogen peroxide content increased continuously during fruit development and senescence. Superoxide dismutase and peroxidase activities consistently increased during fruit maturation, and the catalase activity displayed a single peak at the mature stage. Ascorbate peroxidase and glutathione reductase activities declined during fruit development, but both were activated in yellow fruit. Monodehydroascorbate reductase activity declined and dehydroascorbate reductase (DHAR) activity increased during fruit growth. DHAR was repressed in yellow fruit. Ascorbate dramatically accumulated and its redox state increased, whereas glutathione was degraded and its redox state declined, with fruit maturation.     

Multivitamin–Mineral and Vitamins (E + C) Supplementation Modulate Chronic Unpredictable Stress-Induced Oxidative Damage in Brain and Heart of Mice

Brain is a target of stress along with the immune, metabolic, and cardiovascular systems of the body. In the present work, the preventive roles of a multivitamin–mineral supplement and vitamins (E + C) in chronic unpredictable stress (CUS)-induced oxidative damage were studied in the brain and heart of Swiss albino mice. Thirty-two mice were randomized to one of the following groups: control + vehicle, CUS + vehicle, CUS + multivitamin–mineral, and CUS + vitamins (E + C). CUS was applied for 4 weeks, and multivitamin–mineral and vitamins (E + C) were administered orally for the same period. CUS led to a negative impact on all the biochemical parameters analyzed. Elevation in malondialdehyde and reduction in glutathione levels were found. The activities of superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase were decreased. Treatment with multivitamin–mineral and vitamins (E + C) brought these parameters to near normal levels. Multivitamin–mineral was found more restitutive than combined vitamins (E + C) doses. The present study hypothesizes that supplementation with a multivitamin–mineral may prove more effective than vitamin treatment alone in the alleviation of oxidative damage in brain and heart during periods of chronic stress.     

Use of the inhibition of enzymatic antioxidant systems in order to evaluate their physiological importance

Chemical inhibitors of the different antioxidant enzymes were systematically testet either on purified enzymes of after incubation with human fibroblasts in culture. Inhibition values were obtained for catalase with aminotriazole, for superoxide dismutase with diethyldithiocarbamate, for glutathione peroxidase with mercaptosuccinate, for glutathione reductase with bischloroethylnitrosourea and for glutathione synthesis with buthionine sulfoximine. Viability of cells incubated with these inhibitors was then tested under normal conditions and under high oxygen pressure; the data were correlated with the above-mentioned inhibitory values. Cell viability was particularly affected when the glutathione-related enzymes, especially glutathione peroxidase, were inhibited.     

Water relations, activities of antioxidants, ethylene evolution and membrane integrity of pigeonpea roots as affected by soil moisture

The plants of pigeonpea (Cajanus cajan L.) cv. H77-216 were subjected to moderate [soil moisture content (SMC) = 7.3 ± 0.5 %] and severe (SMC = 4.3 ± 0.5 %) drought by withholding the irrigation at vegetative stage (45 d after sowing). The control plants were maintained at SMC of 11.0 ± 0.5 %. Half of the stressed plants were re-irrigated and their recovery was studied after 2 d. Leaf water potential, osmotic potential, and relative water content of leaf and root decreased significantly while a sharp rise in proline and total soluble sugars contents were noticed. Drought induced a significant increase in 1-aminocyclopropane 1-carboxylic acid (ACC) content and ACC oxidase activity which caused a considerable increase in ethylene evolution. Malondialdehyde content and relative stress injury were increased under drought whereas reverse was true for ascorbic acid content. The membrane integrity of roots decreased during stress and recovered on rehydration. The specific activity of total superoxide dismutase, ascorbate peroxidase, glutathione reductase, and glutathione transferase decreased to 37 – 78 %, 17 – 62 %, 29 – 36 % and 57 – 79 % at moderate and severe drought, respectively. The increase in activity of catalase and peroxidase could not overcome the accumulation of H₂O₂ content in the roots.     

Stability of the anti-oxidative enzymes in aqueous and detergent solution

Activities of the anti-oxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase were studied in rat tissues to determine the ability of detergents both to solubilize the enzymes and also to stabilize enzyme activity. Rat brain, heart and liver were homogenized in 0.1M KCl, 0.1% sodium dodecyl sulfate, 0.1% lubrol, or 0.1% cetyl-trimethylammonium bromide. In general lubrol was more effective than the other solutions in solubilizing GPx and catalase. Lubrol and 0.1M KCl were equally effective in solubilizing SOD. The highest enzyme activities were (1) SOD: 2484 ng/mg (brain), 2501 ng/mg (heart), and 5586 ng/mg (liver); (2) GPx: 224 mU/mg (brain), 1870 mU/mg (heart), and 7332 mU/mg (liver); (3) catalase: 2.8 mU/mg (brain), 10.6 mU/mg (heart), and 309 mU/mg (liver). While cetyl trimethylammonium bromide is marginally better than sodium dodecyl sulfate in solubilizing active enzyme, neither ionic detergent has any advantage over lubrol or 0.1M KCl. For catalase and GPx, enzyme activity loss with time is biphasic. After initial, rapid activity loss (1–5 days for GPx and 7–10 days for catalase) the differences noted among the homogenizing solutions disappear and very little if any activity loss is noted over the next 2–3 weeks. For catalase and GPx, only baseline enzyme activity from t = 0 – 3 weeks is found in the most chaotropic solution, 0.1% sodium dodecyl sulfate while biphasic activity loss is most pronounced in 0.1% lubrol. These results may indicate active GPx and catalase species stabilized by a lipid-like environment. Correlatingin vitro catalase or GPx measurements within vivo anti-oxidative protection may underestimate tissue defences.     

Protection by ebselen against cisplatin-induced nephrotoxicity: Antioxidant system

This study was designed to investigate the cisplatin-induced alteration in renal antioxidant system and the nephroprotection with ebselen. Male Wistar rats were injected with (1) vehicle control; (2) cisplatin; (3) ebselen; and (4) cisplatin plus ebselen. Rats were sacrificed three days post-treatment and plasma as well as kidney were isolated and analyzed. Plasma creatinine increased 598% following cisplatin administration alone which decreased by 158% with ebselen pretreatment. Cisplatin-treated rats showed a depletion of renal glutathione (GSH) levels (52% of control), while cisplatin plus ebselen injected rats had GSH values close to the controls. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased 38, 75 and 62% of control, respectively, and malondialdehyde (MDA) levels increased 174% of control following cisplatin administration, which were restored to control levels after ebselen treatment. The renal platinum level did not significantly change with ebselen pretreatment. This study suggests that the protection offered by ebselen against cisplatin-induced nephrotoxicity is partly related to the sparing of antioxidant system.