Chemomodulatory effects of Terminalia chebula against nickel chloride induced oxidative stress and tumor promotion response in male Wistar rats

Nickel, a major environmental pollutant is a known potent nephrotoxic agent. In this communication we report the chemopreventive effect of Terminalia chebula on nickel chloride (NiCl₂) induced renal oxidative stress, toxicity and cell proliferation response in male Wistar rats. Administration of NiCl₂ (250 μmoL Ni/kg body weight) to male Wistar rats resulted in an increase in the reduced renal glutathione content (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H₂O₂ generation, blood urea nitrogen (BUN) and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (p<0.001). Nickel chloride (NiCl₂) treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [³H] incorporation into renal DNA (p<0.001). Prophylactic treatment of rats with T. chebula (25 mg/kg body weight and 50 mg/kg body weight) daily for one week resulted in the diminution of NiCl₂ mediated damage as evident from the down regulation of glutathione content, GST, GR, LPO, H₂O₂ generation, BUN, serum creatinine, DNA synthesis (p<0.001) and ODC activity (p<0.01) with concomitant restoration of GPx activity. Thus, the present investigation suggests that T. chebula extract could be used as therapeutic agent for cancer prevention as evident from this study where it blocks or suppresses the events associated with chemical carcinogenesis.     

Metformin protects against seizures,learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice

Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200 mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.     

Quercetin mitigates the deoxynivalenol mycotoxin induced apoptosis in SH-SY5Y cells by modulating the oxidative stress mediators

Deoxynivalenol (DON) is Fusarium mycotoxin that is frequently found in many cereal-based foods, and its ingestion has a deleterious impact on human health. In this investigation, we studied the mechanism of DON-induced neurotoxicity and followed by cytoprotective efficacy of quercetin (QUE) in contradiction of DON-induced neurotoxicity through assessing the oxidative stress and apoptotic demise in the human neuronal model, i.e. SH-SY5Y cells. DON diminished the proliferation of cells in the manner of dose and time-dependent as revealed by cell viability investigations, i.e. MTT and lactate dehydrogenase assays. Additional studies, such as intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), DNA damage, cell cycle, and neuronal biomarkers (amino acid decarboxylase, tyrosine hydroxylase, and brain-derived neurotrophic factor) demonstrated that DON induces apoptotic demise in neuronal cells through oxidative stress intermediaries. On another hand, pre-treatment of neuronal cells with 1 mM of quercetin (QUE) showed decent viability upon exposure to 100 µM of DON. In detailed studies demonstrated that QUE (1 mM) pre-treated cells show strong attenuation efficiency against DON-induced ROS generation, LPO, MMP loss, DNA impairment, cell cycle arrest, and down-regulation of neuronal biomarkers. The consequences of the investigation concluded that QUE mitigates the DON-induced stress viz., decreased ROS production and LPO generation, upholding MMP and DNA integrity and regulation of neuronal biomarker gene expression in SH-SY5Y cells.     

Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats

Nickel (Ni), a major environmental pollutant, is known for its wide toxic manifestations. In the present study caffeic acid (CA), one of the most commonly occurring phenolic acids in fruits, grains and dietary supplements, was evaluated for its protective effect against the Ni induced oxidative damage in liver. In this investigation, Ni (20 mg/kg body weight) was administered intraperitoneally for 20 days to induce toxicity. CA was administered orally (15, 30 and 60 mg/kg body weight) for 20 days with intraperitoneal administration of Ni. Ni induced liver damage was clearly shown by the increased activities of serum hepatic enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) along with increased elevation of lipid peroxidation indices (thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides). The toxic effect of Ni was also indicated by significantly decreased levels of enzymatic (superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (glutathione (GSH), vitamin C and vitamin E). CA administered at a dose of 60 mg/kg body weight significantly reversed the activities of hepatic marker enzymes to their near normal levels when compared with other two doses. In addition, CA significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. All these changes were supported by histological observations. The results indicate that CA may be beneficial in ameliorating the Ni induced oxidative damage in the liver of rats.     

Lead-induced oxidative damage in rats/mice: A meta-analysis

BackgroundLead (Pb) is ubiquitous in the environment and is an environmental genotoxic metal. Pb accumulation in the body could cause the oxidative stress.ObjectiveThis meta-analysis aimed to perform a systematic evaluation of the extent of oxidative damage in rats/mice induced by lead.MethodsAll relevant articles in English or Chinese were retrieved from Embase, PubMed, Web of Science, Medline, China National Knowledge Infrastructure, and Chinese Biological Medicine databases from their inception date until July 22, 2018.ResultsA total of 108 eligible articles were included in this study. The indicators of oxidative stress included malondialdehyde (MDA), glutathione disulfide (GSSG), reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione-s-transferase (GST). The meta-analysis showed that lead significantly increased oxidants levels, such as MDA, GSSG, ROS, and H₂O₂ (P < 0.05), and significantly reduced the level of antioxidants, such as CAT, GPx, GR, GSH, SOD, and GST (P < 0.05). The intraperitoneal mode was more effective than water drinking mode in reducing the levels of CAT, GPx, GSH, and SOD (P < 0.05). Other factors that influenced the overall oxidative stress, including species of animals, type of tissues, and intervention dosage and time, were comprehensively evaluated.ConclusionThe results of meta-analysis indicated that mice were more sensitive to lead than rats, and intraperitoneal mode was an effective intervention mean. High doses and long periods of lead treatment can cause serious oxidative damage. Moreover, testicular was more vulnerable to lead than other tissues. These results provided scientific evidence for preventing and treating lead toxicity.     

Ferritin heavy chain as main mediator of preventive effect of metformin against mitochondrial damage induced by doxorubicin in cardiomyocytes

The efficacy of doxorubicin (DOX) as an antitumor agent is greatly limited by the induction of cardiomyopathy, which results from mitochondrial dysfunction and iron-catalyzed oxidative stress in the cardiomyocyte. Metformin (MET) has been seen to have a protective effect against the oxidative stress induced by DOX in cardiomyocytes through its modulation of ferritin heavy chain (FHC), the main iron-storage protein. This study aimed to assess the involvement of FHC as a pivotal molecule in the mitochondrial protection offered by MET against DOX cardiotoxicity. The addition of DOX to adult mouse cardiomyocytes (HL-1 cell line) increased the cytosolic and mitochondrial free iron pools in a time-dependent manner. Simultaneously, DOX inhibited complex I activity and ATP generation and induced the loss of mitochondrial membrane potential. The mitochondrial dysfunction induced by DOX was associated with the release of cytochrome c to the cytosol, the activation of caspase 3, and DNA fragmentation. The loss of iron homeostasis, mitochondrial dysfunction, and apoptosis induced by DOX were prevented by treatment with MET 24 h before the addition of DOX. The involvement of FHC and NF-κB was determined through siRNA-mediated knockdown. Interestingly, the presilencing of FHC or NF-κB with specific siRNAs blocked the protective effect induced by MET against DOX cardiotoxicity. These findings were confirmed in isolated primary neonatal rat cardiomyocytes. In conclusion, these results deepen our knowledge of the protective action of MET against DOX-induced cardiotoxicity and suggest that therapeutic strategies based on FHC modulation could protect cardiomyocytes from the mitochondrial damage induced by DOX by restoring iron homeostasis.     

Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats

BackgroundExcessive exposure to iron can cause kidney damage, and chelating drugs such as deferoxamine and deferiprone have limited usefulness in treating iron poisoning. This study was designed to investigate the protective effects of grape seed proanthocyanidins (GSPAs) against iron overload induced nephrotoxicity in rats. The roles of GSPAs in chelating iron, antioxidant activity, renal function, pathological section, and apoptosis-related gene expression were assessed.MethodsNewly weaned male Sprague–Dawley rats aged 21 days (weight, 65 ± 5 g) were randomly divided into four groups containing 10 rats each: normal control (negative) group, iron overload (positive) group, GSPAs group, and GSPAs + iron overload (test) group. Iron dextran injections (2.5 mg⋅ kg⁻¹) and GSPAs (25 mg⋅ kg⁻¹) were intraperitoneally and intragastrically administered to rats daily for 7 weeks, respectively. Measurements included red blood cell (RBC) count and hemoglobin (Hb) level, serum total iron-binding capacity (TIBC), renal iron content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant activity (T-AOC), creatinine (CR) and blood urea nitrogen (BUN) levels, pathological changes, and apoptotic Fas, Bax expressions in the kidney tissue. Differences among the dietary groups were determined using one-way analysis of variance with post-hoc Tukey’s test. P < 0.05 was considered statistically significant.ResultsRBC count, Hb level, renal iron content, MDA content, CR and BUN levels, and Fas, Bax expressions significantly increased in the positive group than in the negative group; contrarily, TIBC, GSH-Px activity, and T-AOC significantly decreased in the positive group than in the negative group (P < 0.05). Although not statistically significant, SOD activity was slightly reduced in the positive group than in the negative group. Inflammatory cell infiltration and fibrous tissue proliferation were observed in the kidney tissue of the rats in the positive group; in contrast, the rats exhibited better recovery when GSPAs were used instead of iron alone. Compared with the positive group, RBC counts, Hb levels, renal iron contents, the MDA content, CR and BUN levels, and Fas, Bax expressions significantly decreased, whereas the TIBC, the GSH-Px and SOD activities as well as T-AOC significantly increased in the test group rats (P < 0.05). There were no significant differences in the RBC counts, Hb levels, TIBC, renal iron contents, the SOD activity and MDA content, CR and BUN levels, and Fas expression between the GSPAs and negative groups. The GSH-Px activity and T-AOC were significantly increased whereas Bax expression was significantly decreased in the GSPAs group rats than in the negative group rats (P < 0.05). The rats in the GSPAs, test, and negative groups displayed glomeruli and tubules with a clear structure; further, the epithelial cells in the renal tubules were neatly arranged.ConclusionsGSPAs have protective effects on nephrotoxicity in rats with iron overload. Thus, further investigation of GSPAs as a new and natural phytochemo-preventive agent against iron overload is warranted.     

Protective effects of polyunsatutared fatty acids supplementation against testicular damage induced by intermittent hypobaric hypoxia in rats

Background

Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of the work was to test whether PUFA supplementation attenuates oxidative damage in testis by reinforcing the antioxidant defense system. The animals were divided into four groups (7 rats per group): normobaric normoxia (~750 tor; pO2 156 mmHg; Nx); Nx + PUFA, supplemented with PUFA (DHA: EPA = 3:1; 0.3 g kg⁻¹ of body weight per day); hypoxic hypoxia (~428 tor; pO2 90 mmHg; Hx) and, Hx + PUFA. The hypoxic groups were exposed in 4 cycles to 96 h of HH followed by 96 h of normobaric normoxia for 32 days. Total antioxidant capacity (FRAP) and lipid peroxidation (malondialdehyde, MDA) in plasma and reduced (GSH)/oxidized glutathione (GSSG) ratio, tissue lipid peroxidation (TBARS) and antioxidant enzymes activity were assessed at the end of the study in testis. Also, SIRTUIN 1 and HIF-1 protein expression in testis were determined.

Results

IHH increased lipid peroxidation in plasma and HIF-1 protein levels in testis. In addition, IHH reduced FRAP levels in plasma, antioxidant enzymes activities and SIRTUIN 1 protein levels in testis. PUFA supplementation attenuated these effects, inducing the increases in FRAP, in the antioxidant enzymes activity and HIF-1 levels.

Conclusions

These results suggest that the IHH model induces a prooxidant status in plasma and testis. The molecular protective effect of PUFA may involve the induction of an antioxidant mechanism.     

Effect of testosterone on oxidative stress and cell damage induced by 3-nitropropionic acid in striatum of ovariectomized rats

This paper evaluates the effects of testosterone (0.5 mg/kg subcutaneously (s.c.) for 8 days) on oxidative stress and cell damage induced by 3-nitropropionic acid (20 mg/kg intraperitoneally (i.p.) for 4 days) in ovariectomized rats. Gonadectomy triggered oxidative damage and cell loss, evaluated by the detection of caspase-3, whereas 3-nitropropionic acid increased the levels of oxidative stress induced by ovariectomy and prompted cell damage characterized by enhanced levels of lactate dehydrogenase. These changes were blocked by testosterone administration. Our results support the following conclusions: i) ovariectomy triggers oxidative and cell damage via caspase-3 in the striatum; ii) 3-nitropropionic acid exacerbates oxidative stress induced by ovariectomy and leads to cell damage characterized by increased levels of lactate dehydrogenase; iii) testosterone administration decreases oxidative stress and cell damage. Additionally, these data support the hypothesis that testosterone might play an important role in the onset and development of neurodegenerative diseases.     

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDD-induced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDD-induced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na⁺-K⁺ and Mg²⁺ATPases activities with increase in Ca²⁺ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.     

Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats

Diabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45 mg kg⁻¹, i.p.) injection into rats. Two days after streptozotocin treatment 10 μM kg⁻¹ day⁻¹ CAPE was administrated and continued for 60 days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-α, 26% for IFN-γ) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-α and IFN-γ in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.     

Apple juice attenuates genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of rats

The aim of this study was to evaluate the health benefits associated with apple consumption following cadmium exposure. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (non-treated group, CTRL); cadmium group (Cd) and apple juice group (Cd + AJ). The results showed a decrease in the frequency micronucleated cells in bone marrow and hepatocytes in the group exposed to cadmium and treated with apple juice. Apple juice was also able to reduce the 8OHdG levels and to decrease genetic damage in liver and peripheral blood cells. Catalase (CAT) was decreased following apple juice intake. Taken together, our results demonstrate that apple juice seems to be able to prevent genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.     

Genistein abrogates pre-hemolytic and oxidative stress damage induced by 2,2'-Azobis (Amidinopropane)

The pre-hemolytic mechanism induced by free radicals initiated from water-soluble 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) and its reversal by genistein was investigated in human erythrocytes. The time course of K+ efflux compared to the occurrence of hemolysis suggests that AAPH-induced hemolysis occurs indirectly via pore formation and band 3 oxidation as expected. However, genistein inhibited hemolysis, LDH release and membrane protein oxidation but not K+ efflux. This indicated that erythrocyte protein oxidation possibly in the hydrophobic core plays a significant role in the membrane pre-hemolytic damage. Chemiluminescence (CL) analysis carried out in non-lysed erythrocytes treated with AAPH showed a dramatic increase in CL indicating both reduced levels of antioxidants and increased membrane lipid peroxide. The V0 value was also increased up to 6 times, denoting a high degree of membrane peroxidation very early in erythrocyte membrane damage. The whole process was inhibited by genistein in a dose-dependent manner. These results indicate that the genistein inhibited both hemolysis and pre-hemolytic damage and also hindered membrane lipid peroxide formation and protein oxidation. In addition, it is suggested that pre-hemolytic damage is mediated mainly by the oxidation of both phospholipid and protein located in the deeper hydrophobic region of the membrane.     

Hypermethioninemia provokes oxidative damage and histological changes in liver of rats

In the present study we evaluated the effect of chronic methionine administration on oxidative stress and biochemical parameters in liver and serum of rats, respectively. We also performed histological analysis in liver. Results showed that hypermethioninemia increased chemiluminescence, carbonyl content and glutathione peroxidase activity, decreased total antioxidant potential, as well as altered catalase activity. Hypermethioninemia increased synthesis and concentration of glycogen, besides histological studies showed morphological alterations and reduction in the glycogen/glycoprotein content in liver. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glucose were increased in hypermethioninemic rats. These findings suggest that oxidative damage and histological changes caused by methionine may be related to the hepatic injury observed in hypermethioninemia.     

Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones

Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01), glutathione metabolizing enzymes (P < 0.001) and antioxidant enzymes were also returned to normal levels (P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response in Wistar rats.     

Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats

Background

Effect of aqueous extracts of Allium sativum (garlic), Zingiber officinale (ginger), Capsicum fructensces (cayenne pepper) and their mixture on oxidative stress in rats fed high Cholesterol/high fat diet was investigated. Rats were randomly distributed into six groups (n = 6) and given different dietary/spice treatments. Group 1 standard rat chow (control), group 2, hypercholesterolemic diet plus water, and groups 3, 4, 5, 6, hypercholesterolemic diet with 0.5 ml 200 mg · kg-1 aqueous extracts of garlic, ginger, cayenne pepper or their mixture respectively daily for 4 weeks.

Results

Pronounced oxidative stress in the hypercholesterolemic rats evidenced by significant (p < 0.05) increase in MDA levels, and suppression of the antioxidant enzymes system in rat’s liver, kidney, heart and brain tissues was observed. Extracts of spices singly or combined administered at 200 mg.kg-1 body weight significantly (p < 0.05) reduced MDA levels and restored activities of antioxidant enzymes.

Conclusions

It is concluded that consumption of garlic, ginger, pepper, or their mixture may help to modulate oxidative stress caused by hypercholesterolemia in rats.     

Dimethylthiourea protects against mitochondrial oxidative damage induced by cisplatin in liver of rats

Cisplatin is one of the most effective chemotherapeutic agents. However, at higher doses liver injury may occur. The purpose of this study was to explore whether the hydroxyl radical scavenger dimethylthiourea (DMTU) protects against cisplatin-induced oxidative damage in vivo and to define the mitochondrial pathways involved in cytoprotection. Adult male Wistar rats (200–220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The DMTU group was given only DMTU (500 mg/kg body weight, i.p), followed by 125 mg/kg body weight, i.p. (twice a day) until sacrifice. The cisplatin group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The DMTU + cisplatin group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until sacrifice (72 h after the treatment). DMTU did not present any direct effect on mitochondria and substantially inhibited cisplatin-induced mitochondrial damage in liver, therefore preventing elevation of AST and ALT serum levels. DMTU protected against (a) decreased hepatic ATP levels; (b) lipid peroxidation; (c) cardiolipin oxidation; (d) sulfhydryl protein oxidation; (e) mitochondrial membrane rigidification; (f) GSH oxidation; (g) NADPH oxidation; (h) apoptosis. Results suggest that antioxidants, particularly hydroxyl radical scavengers, protect liver mitochondria against cisplatin-induced oxidative damage. Several mitochondrial changes were delineated and proposed as interesting targets for cytoprotective strategy.