Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats

The aim of this study was to investigate the effects of lycopene on cisplatin-induced nephrotoxicity and oxidative stress in rats. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group (group 1) received physiological saline; animals in group 2 received only cisplatin; a 10 days of lycopene pre-treatment was applied to the animals in group 3 before administration of cisplatin; a 5 days of lycopene treatment was performed following administration of cisplatin for the animals in group 4. Cisplatin (7 mg/kg) was intraperitoneally injected as a single dose and lycopene (4 mg/kg) was administered by gavage in corn oil. Biochemical and histopathological methods were utilised for evaluation of the nephrotoxicity. The concentrations of creatinine, urea, Na+ and K+ in plasma and levels of malondialdehyde and reduced glutathione as well as glutathione peroxidase and catalase activities were determined in kidney tissue. Administration of cisplatin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Na+ and K+ levels of rats received cisplatin alone were not significantly different compared to control group, but they had higher kidney malondialdehyde, and lower reduce glutathione concentrations, glutathione peroxidase and catalase activities. Lycopene administration produced amelioration in biochemical indices of nephrotoxicity in both plasma and kidney tissues when compared to group 2; pre-treatment with lycopene being more effective. Results from this study indicate that the novel natural antioxidant lycopene might have protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat.     

Protective roles of onion and garlic extracts on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to assess the possible protective roles of onion (Allium cepa Linn) and garlic (Allium sativum Linn) extracts on Cd-induced testicular damage and spermiotoxicity. The control group received double distilled water; Cd group received Cd (1.5mg/100g BW/day) orally; extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5ml and 1.0ml/100g BW/day) orally for one week and then simultaneously challenged with Cd (1.5mg/100g BW/day) for additional three weeks. Testicular tissue oxidant/antioxidant status and sperm characteristics were determined. Cd caused a marked (p<0.001) rise in testicular lipid peroxidation (LPO) and glutathione S-transferase (GST) levels whereas glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and alkaline phosphatase (ALP) levels were decreased. Cd intoxication significantly (p<0.001) decreased epididymal sperm concentration and sperm progress motility, increased percent total sperm abnormalities and live/dead count. Both extracts successfully attenuated these adverse effects of Cd. Onion extract offers a dose-dependent protection. Our study demonstrated that aqueous extracts of onion and garlic could proffer a measure of protection against Cd-induced testicular oxidative damage and spermiotoxicity by possibly reducing lipid peroxidation and increasing the antioxidant defence mechanism in rats.     

The effects of desferrioxamine on cisplatin-induced lipid peroxidation and the activities of antioxidant enzymes in rat kidneys

Cisplatin-induced nephrotoxicity is associated with an increase in lipid peroxidation and oxygen free radicals in rat kidneys. In this study, the effects of desferrioxamine were compared to vitamin C and E on cisplatin-induced lipid peroxidation and antioxidant enzyme activities in rat kidneys. Rats were divided into five groups, with 15 Wistar rats in each group. In the control group, rats received 1 mL/100 g isotonic saline solution intraperitoneally (i.p.). In Group II, 10 mg/kg cisplatin i.p. was injected to rats. Thirty minutes before the same dosage of cisplatin administration, 100 mg/kg i.p. vitamin C or E was given to rats in groups III and IV, respectively. Rats in Group V received 250 mg/kg desferrioxamine i.p., before the same dose of cisplatin administration. All rats were killed by cervical dislocation after 72 hours. The kidneys were immediately removed and washed in cold saline. Spectrophotometric method was used for all analyses. While catalase, glutathione reductase (GR), and superoxide dismutase (SOD) levels were found to be significantly decreased (P < 0.001), malondialdehyde (MDA) (P < 0.05) and hydrogen peroxide (H2O2) (P < 0.001) levels were significantly increased in the cisplatin group when compared to the controls. MDA levels were decreased by desferrioxamine (P < 0.005) as well as vitamin C and E (P < 0.05 and P < 0.001, respectively). These three compounds induced a significant increase in SOD levels (P < 0.05), but only in the vitamin C group, were SOD levels not significantly different than the levels of the controls (P > 0.05). In the desferrioxamine (P < 0.05), vitamin C and E groups (P < 0.001 for both), the cisplatin elevated H2O2 levels were decreased. None of these drugs had any effect on GR and catalase levels (P > 0.05). Desferrioxamine is useful to prevent cisplatin-induced lipid peroxidation, however, vitamin C and E are more effective on antioxidant enzymes than desferrioxamine.     

Toxic Effect of Cyclophosphamide on Sperm Morphology,Testicular Histology and Blood Oxidant‐Antioxidant Balance,and Protective Roles of Lycopene and Ellagic Acid

Abstract: In this study, the toxic effect of cyclophosphamide (CP) on sperm morphology, testicular histology and blood oxidant–antioxidant balance, and protective roles of lycopene (LC) and ellagic acid (EA) were investigated. For this purpose, 48 healthy, adult, male Sprague‐Dawley rats were divided into six groups; eight animals in each group. The control group was treated with placebo. LC, EA and CP groups were given alone LC (10 mg/kg/every other day), EA (2 mg/kg/every other day) and CP (15 mg/kg/week) respectively. One of the last two groups received CP + LC, and the other treated with CP + EA. All treatments were maintained for 8 weeks. At the end of the treatment period, morphological abnormalities of sperm, plasma malondialdehyde (MDA) levels and glutathione (GSH) levels, and GSH‐peroxidase (GSH‐Px), catalase (CAT) and superoxide dismutase (SOD) activities in erythrocytes, and testicular histopathological changes were examined. CP administration caused statistically significant increases in tail and total abnormality of sperm, plasma MDA level and erythrocyte SOD activity, and decreases in erythtocyte CAT activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen’s Testicular Score along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue. However, LC or EA treatments to CP‐treated rats markedly improved the CP‐induced lipid peroxidation, and normalized sperm morphology and testicular histopathology. In conclusion, CP‐induced lipid peroxidation leads to the structural damages in spermatozoa and testicular tissue of rats, and also LC or EA have a protective effect on these types of damage.     

Carvedilol alleviates testicular and spermatological damage induced by cisplatin in rats via modulation of oxidative stress and inflammation

The clinical application of the anticancer drug cisplatin is limited by its deleterious side effects, including male reproductive toxicity. In this context, the potential protective effect of carvedilol on testicular and spermatological damage induced by cisplatin in male Sprague–Dawley rats was investigated. Carvedilol was orally administered at a dose of 10 mg/kg for 2 weeks, and cisplatin was given as a single intraperitoneal injection of 10 mg/kg on the 12th day to induce toxicity. Cisplatin significantly reduced reproductive organ weight, sperm count and sperm motility, and increased sperm abnormalities and histopathological damage of testicular tissue. In addition, it resulted in a significant decline in serum testosterone as well as levels of testicular enzymatic and non-enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxides, and reduced glutathione). Moreover, cisplatin remarkably augmented malondialdehyde, nitric oxide, tumor necrosis factor-α, and nuclear factor-kappa B contents in testicular tissue. Conversely, carvedilol administration markedly mitigated cisplatin-induced testicular and spermatological injury as demonstrated by suppression of oxidative/nitrosative and inflammatory burden, amendment of antioxidant defenses, enhancement of steroidogenesis and spermatogenesis, and mitigation of testicular histopathological damage. The current study reveals a promising protective action of carvedilol against cisplatin-induced reproductive toxicity by virtue of its anti-inflammatory and antioxidant properties.     

Mitochondrial dysfunction induced impairment of spermatogenesis in LPS-treated rats: modulatory role of lycopene

The current study investigates the potential toxicity of lipopolysaccharide (LPS) on the mitochondrial fraction of rat testis and the possible protective efficacy of lycopene. Adult male Wistar rats were categorized into four groups. Two groups were administered LPS (0.1mg/kg/day for 7 days i.p.); one of these groups received lycopene treatment (4 mg/kg/day by oral gavage, 24h before LPS treatment) (Group IV) and the other received LPS alone (Group III). A vehicle-treated group (Group I) and a lycopene drug control group (Group II) were also included. Sperm count and motility were significantly decreased in Group III. The testicular mitochondrial fraction of Group III showed significant increase in basal and Fe(2+)-induced lipid peroxidation, along with a significant increase in hydrogen peroxide (H(2)O(2)) level. Moreover, the activities of mitochondrial enzymic (SOD, CAT, GPx, GR and ADH) and non-enzymic (GSH and ascorbate) antioxidants levels were decreased. Group III also showed decline in the activities of TCA enzymes such as SDH, MDH and ICDH. Pretreatment with lycopene showed normal sperm parameters, lipid peroxidation, H(2)O(2) level, antioxidant defenses and TCA enzyme activities. In conclusion, this study indicates that LPS-induced oxidative stress leads to functional damages in the testicular mitochondria. Lycopene pretreatment provided a marked normalization in these parameters.     

Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse liver

This study evaluates whether quercetin (25, 50 and 75 mg/kg body weight) treatment has a protective effect on the pro-oxidant-antioxidant state following chronic ethanol treatment in mice. Pretreatment (quercetin 25, 50 and 75 mg/kg body weight for 15 d+co-treatment of ethanol 18%+quercetin for 15 d and ethanol 18% for the 15 d) increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH) in comparison to the ethanol group. No significant differences from the ethanol group were observed in the group after post-treatment (ethanol 18% for 30 d+quercetin 25, 50 and 75 mg/kg body weight for 15 d) with quercetin. A significant increase in lipid peroxidation (malondialdehyde, MDA) products was observed in liver tissue after administration of ethanol, which was attenuated by pre- and post-treatment with a high dose of quercetin. GSH levels increased and oxidized glutathione (GSSG) levels decreased in groups of ethanol-exposed mice that received quercetin for 15 d prior to ethanol exposure. In conclusion, pre-treatment of quercetin may protect against ethanol-induced oxidative stress by directly quenching lipid peroxides and indirectly by enhancing the production of the endogenous antioxidant GSH. There was no protective effect on post-treatment with quercetin.     

Attenuating effect of lycopene and ellagic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced spermiotoxicity and testicular apoptosis

This study was conducted to investigate the prophylactic effects of lycopene (LC) and ellagic acid (EA) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular and spermatozoal toxicity. These toxicological changes are associated with the oxidative stress and apoptosis in male rats. Forty-eight male rats were allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC, and TCDD+EA. The control group was treated with 0.5?mL/rat slightly alkaline solution+0.5?mL/rat corn oil every other day. The LC group was treated with 0.5?mL/rat slightly alkaline solution+0.5?mL/rat corn oil containing 10?mg/kg of LC every other day. The EA group received 0.5?mL/rat corn oil+0.5?mL/rat slightly alkaline solution containing 2?mg/kg of EA every other day. The TCDD group received 0.5?mL/rat corn oil containing 100?ng/kg/day of TCDD+0.5?mL/rat slightly alkaline solution. The TCDD+LC group was treated with 0.5?mL/rat TCDD+0.5?mL/rat LC. The TCDD+EA group was treated with 0.5?mL/rat TCDD+0.5?mL/rat EA. All treatments were made by gavage, and the experimental period was maintained during 8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity, histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were determined. TCDD exposure resulted in significant decreases in sperm motility, concentration, testicular superoxide dismutase activity, germinal cell-layer thickness, Johnsen's testicular score, and significant increases in abnormal sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive staining, and Bax-positive apoptotic cell score, along with some testicular histopathological lesions. TCDD treatment did not affect significantly catalase activity. However, combined treatment with LC or EA, in addition to TCDD, prevented the development of TCDD-induced damages in sperm quality, testicular histology, and LPO. Improvements in testicular apoptosis after the administration of LC and EA to TCDD-treated rats were minimal, but not statistically significant. TCDD-induced lipid peroxidation leads to functional and structural damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protected against the development of these effects.     

Spermatotoxicity,biochemical changes and histological alteration induced by gossypol in testicular and hepatic tissues of male rats

Gossypol acetic acid (GAA) displays anti-fertility and antioxidant behavior. The efficacies of different doses of gossypol acetic acid were investigated in male albino rats. Rats were allocated into four groups: control group and three GAA-treated groups (2–4), that were injected with GAA (5, 10, 20 mg/kg BW, respectively), through inrtaperitonial injection. Treatment of GAA was found to elicit a significant decrease in sperm counting, sperm motility, serum levels of testosterone, luteinizing hormone and follicle-stimulating hormone, whereas, the activities of testicular 17β-hydroxysteroid dehydrogenase and 17-ketosteroid reductase were increased. The activities of serum transaminases and alkaline phosphatase and hepatic glutathione peroxidase; glutathione reductase, superoxide dismutase and glutathione S-transferase and the level of hepatic glutathione were elevated. While, the lipid peroxidation end product; malondialdehyde, nitric oxide, and lipid profile and the activity of hepatic cytochrome P450 were decreased in GAA-treated rats. The histological analysis of liver and testicular tissues showed sever hepatocyte damage in addition to abnormal localization of hepatocytic nuclei. Also, the testicular pathology of GAA-treated rats showed depressed spermatogensis, sertoli cell toxicity and degeneration of seminiferous tubules.     

Modulatory Effects of Lycopene and Ellagic Acid on Reproductive Dysfunction Induced by Polychlorinated Biphenyl (Aroclor 1254) in Male Rats

Abstract: The present study was conducted to investigate the possible protective effects of lycopene (LP) and ellagic acid (EA) on aroclor (AR) 1254‐induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. The control group was treated with placebo. LP (10 mg/kg/every other day), EA (2 mg/kg/every other day) and AR (2 mg/kg/day) groups were given alone LP, EA and AR respectively. One of the last two groups received AR + LP, and the other treated with AR + EA. Body and reproductive organ weights, epididymal sperm characteristics, testicular tissue lipid peroxidation levels, antioxidant enzyme activities, histopathological changes and apoptosis via Bax and Bcl‐2 genes were investigated. AR administration caused statistically significant decreases in body‐weight, epididymal sperm concentration, testicular superoxide dismutase activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen’s testicular score, and increases in relative weights of testis, epidydimis and seminal vesicles, rates of abnormal sperm and apoptotic cell expression along with degeneration, desquamation and disorganization in spermatogenic cells, and interstitial oedema and congestion in testicular tissue. LP and EA treatments to AR‐treated rats markedly decreased abnormal sperm rates, testicular thiobarbituric acid reactive substances level, and increased the glutathione (GSH) level, GSH‐peroxidase, catalase activities and epidiymal sperm concentration as compared with the alone AR group. Additionally, the AR‐induced histopathological damages were totally or partially recovered by LP or EA administrations respectively. AR damages the testicular tissue and spermatozoa by impairing the oxidant/antioxidant balance and by increasing the apoptotic spermatogenic cell rates. However, both LP and EA have modulator effects on AR‐induced reproductive dysfunction in male rats.     

Protective effect of lycopene on adriamycin-induced cardiotoxicity and nephrotoxicity

The aim of this study was to investigate the possible protective role of lycopene on adriamycin (ADR)-induced heart and kidney toxicity using biochemical and histopathological approaches. Rats were randomly divided into four groups. The first group received no medication and was regarded as the control group; the second group was injected with a single dose of ADR; the third group was treated with lycopene for 10 days before ADR injection and the last group was treated with lycopene for 2 days before and for 3 days after the administration of a single dose of ADR. ADR (10mg/kg) was intraperitoneally (i.p.) injected as a single dose and lycopene (4 mg/kg) was administered in corn oil by gavage. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) in both the heart and kidneys were higher in the group treated with ADR alone than in the control group, and were lower in the groups administered with lycopene than in the ADR alone group. Although the activity of catalase (CAT) in the heart was higher in the ADR alone group than in the control group, it was lower in the kidneys. In particular, treatment with lycopene post-injection normalized both cardiac and kidney CAT activities. In heart and kidney tissues, glutathione peroxidase (GSH-Px) activities were not significantly different between all groups. Significant increases in the levels of plasma creatinine and urea were observed in the ADR group when compared to the control group, and these increases were normalized by lycopene treatment. Cardiac and renal histopathological changes were observed in the ADR group as compared to the control group. In contrast, these histopathological changes appeared nearly normal in the groups treated with lycopene pre- and post-injection. In conclusion, this study clearly indicated that ADR treatment markedly impaired cardiac and renal function and that treatment with lycopene might prevent this toxicity in rats.     

Antioxidant enzyme activities and oxidative stress in affective disorders

Recent data from several reports indicate that free radicals are involved in the biochemical mechanisms underlying neuropsychiatric disorders in human. The results of several reports suggest that lower antioxidant defences against lipid peroxidation exist in patients with depression and that there is a therapeutic benefit from antioxidant supplementation in unstable manic-depressive patients. We investigated the antioxidant enzyme status and the indices of oxidative stress and lipid peroxidation end products in erythrocytes from patients with affective disorder. For this purpose, we measured superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels in patients with affective disorders (n=30) in both pre- and post-treatment periods, and in a control group (n=21). CAT activities were significantly decreased in both pre-, and post-treatment periods in patients compared to the control group. GSH-Px activity in the pre-treatment period in the patients was significantly lower than both post-treatment patient and control groups. MDA levels were increased in both pre-, and post-treatment patient groups compared to the control group. NO level was lower in the pre-treatment patient group than in the control group. There were statistically significant correlations between SOD and MDA, and SOD and NO in the pre-treatment patient and control groups. Because the overall study sample was small, and the post-treatment patient group was even smaller, it can tentatively be suggested that the antioxidant system is impaired during a mood episode in patients with affective disorders, normalizing at the end of the episode.     

Responses of testis,epididymis, and sperm of pubertal rats exposed to functionalized multiwalled carbon nanotubes

The present study investigated the response of testes, epididymides and sperm in pubertal Wistar rats following exposure to 0, 0.25, 0.5, 0.75, and 1.0 mg kg^?1 functionalized multi‐walled carbon nanotubes (f‐MWCNTs) for 5 days. The results showed that administration of (f‐MWCNTs) significantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in a dose‐dependent manner in both testes and sperm compared with control group. Moreover, the significant decrease in the activity of glutathione‐S‐transferase and glutathione level was accompanied with significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm of (f‐MWCNTs)‐treated rats. The spermiogram of (f‐MWCNTs)‐treated rats indicated significant decrease in epididymal sperm number, sperm progressive motility, testicular sperm number and daily sperm production with elevated sperm abnormalities when compared with the control. Exposure to (f‐MWCNTs) decreased plasma testosterone level and produced marked morphological changes including decreased geminal epithelium, edema, congestion, reduced spermatogenic cells and focal areas of tubular degeneration in the testes. The lumen of the epididymides contained reduced sperm cells and there was mild to severe hyperplasia epithelial cells lining the duct of the epididymis. Collectively, pubertal exposure of male rats to (f‐MWCNTs) elicited oxidative stress response resulting in marked testicular and epididymides dysfunction. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 543–551, 2016.     

Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods

This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity.     

Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats

We investigated the toxic effect of nevirapine (NVP; Viramune(?)), an antiretroviral drug, on the liver, kidney and testis of Wistar rats. Twenty-one rats were assigned into 3 groups of 7 animals each. The first group served as control, and the second and third groups received NVP at 18 and 36?mg/kg body weight, respectively. Clinical signs of toxicity were not observed in the animals. NVP at both doses did not significantly (p?>?0.05) alter the body weight gain, relative weights of kidney and testis, serum protein, urea, creatinine and alkaline phosphatase levels of the animals. However, NVP2 significantly (p?相似文献   

Mechanism of Cisplatin Ototoxicity: Antioxidant System

Abstract: The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrified and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45±0.012 nmol/mg] after cisplatin administration compared to 0.95±012 nmol/mg in control cochleae (P<0.05). Superoxide dismutase, catalase activities and malondialehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration. Alterations in the activity of antioxidant enzymes, an increase in malondialdehyde levels, and depletion of cochlear GSH suggest a role for reactive oxygen species mediated damage of the cochlea in cisplatin toxicity. These biochemical changes were accompanied by the elevation of ABR threshold that appears to correlate well with alterations in antioxidant systems which could be the cause of cisplatin ototoxicity.     

Influence of combined treatment with zinc and selenium on cadmium induced testicular pathophysiology in rat

The present study was conducted to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced testicular pathophysiology compared to Se or Zn treatment alone in rats. For this purpose, male rats received either tap water, Cd, Cd + Zn, Cd + Se or Cd + Zn + Se in their drinking water, for 35 days. Cd exposure caused a significant decrease in plasma and testicular concentrations of Se and Zn which was accompanied by decreased plasma testosterone level, sperm count and motility, enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) as well as by increased lipid peroxidation (as malondialdehyde, MDA). With Se or Zn administration, during exposure to Cd, only partial corrective effects on depletion of testicular and plasma Se and Zn levels, sperm characteristics and oxidative stress have been observed. The combined treatment of Cd-exposed animals with Se and Zn assured a more significant decrease in plasma and testicular Cd concentrations and a more efficient protection against the observed testicular damage as evidenced by the total prevention of both Se and Zn deprivation and by the entire restoration of the sperm motility and the testicular antioxidant status.     

The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats

The antioxidant activity of the amino acid glutamine was investigated to obtain protection against peroxidative damage in rat kidney and nephrotoxicity induced by the treatment with a single dose of the antitumoral cisplatin (5mgkg(-1) body weight). The animals were divided into four treatment and control groups of six rats each (n=6). Cisplatin was injected i.p. and glutamine (300mgkg(-1) body weight) was given by gavage 24h before the cisplatin injection. After 24h and 7 days of cisplatin administration, the rats were sacrificed. A single dose of cisplatin resulted in significant reduction in body weight and creatinine clearance, and higher urinary volumes were observed in all groups treated with this antitumor drug (P<0.05). Renal tissue from cisplatin-treated rats showed an increase in malondialdehyde production and increase in glutathione contents 24h and 7 days after cisplatin administration. Pretreatment of rats with glutamine substantially inhibited the increase in the levels of renal glutathione induced by cisplatin 24h after the i.p. injection. The malondialdehyde in the renal tissues was significantly reduced 7 days after cisplatin treatment. However, the reduction in the peroxidative damage did not reach the value of the control group. The protective effects obtained by glutamine pretreatment in peroxidative alterations were not observed in the other parameters studied. These results suggest that glutamine partially protect against cisplatin-induced lipid peroxidation damage, but it was not enough to inhibit cisplatin-induced nephrotoxicity in rats.     

Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats

A potential therapeutic approach to protect or reverse gentamicin-induced oxidative stress and nephrotoxicity would have more importance for clinical consequences. Therefore, the present study was designed to investigate the possible protective effects of lycopene against gentamicin-induced renal damage in rats. Male Sprague-Dawley rats were divided into four groups of six rats in each one; first group served as control. The other groups were treated intraperitoneally with gentamicin alone (100 mg kg(-1) per day) for six successive days, gentamicin for 6 days following 10 days of orally lycopene (4 mg kg(-1) per day) pre-treatment and 6-days of simultaneous lycopene and gentamicin. Biochemical and histopathological examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, urea, Na(+) and K(+) levels in plasma and malondialdehyde (MDA), reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney tissue. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and urea concentrations. The animals treated with gentamicin alone showed a significantly higher kidney MDA and lower GSH-Px and CAT activities but unaffected GSH concentrations when compared with the control group. Pre-treatment with lycopene produced amelioration in biochemical indices of nephrotoxicity in plasma. However, little changes were observed in the kidney MDA and GSH levels and GSH-Px and CAT activities when compared with the gentamicin treated group. The histological structures of the renal proximal tubules showed similar patterns. On the other hand, administration of simultaneous lycopene to rats produced amelioration in MDA and GSH levels and GSH-Px and CAT activities when compared with gentamicin group. In addition, simultaneous lycopene was found to reduce the degree of kidney tissue damage in histopathological findings. These results indicate that specially simultaneous treatment of lycopene might have produced amelioration in biochemical indices and oxidative stress parameters against gentamicin-induced nephrotoxicity, but pre-treatments with lycopene had no beneficial effects on these parameters. It was concluded that lycopene as a novel natural antioxidant might have protective effects against gentamicin-induced nephrotoxicity and oxidative stress in rats.     

Simvastatin attenuates cisplatin-induced kidney and liver damage in rats

Statins have anti-inflammatory effects that are not directly related to their cholesterol-lowering activity. This study aimed to investigate the effect of simvastatin on the extent of tissue damage in cisplatin-induced nephrotoxicity and hepatotoxicity. The rats received a single intravenous injection of 2.5 mg kg⁻¹ cisplatin. Other groups received either simvastatin (1 mg kg⁻¹) or the vehicle (ethanol:saline) intraperitoneally for 10 days beginning 5 days prior to cisplatin injection. All animals were decapitated 5 days after cisplatin administration. Trunk blood was collected and analyzed for blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), albumin, and total bilirubin levels. The urine samples were used for the calculation of creatinine clearance levels. The kidney and liver samples were stored for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content or were processed for histopathological examinations. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence method. Simvastation reduced the extent of both kidney and liver damage and preserved both kidney and liver functions (p < 0.01–0.001). Increase in liver MDA level with a concomitant reduction in GSH in the cisplatin group was attenuated by simvastatin treatment (p < 0.05–0.01). Increase in tissue collagen content and chemiluminescence levels in the kidney and liver samples of the cisplatin group was also reversed by simvastatin (p < 0.001). In conclusion, simvastatin is beneficial in cisplatin-induced kidney and liver dysfunction and organ damage in rats via prevention of lipid peroxidation and tissue fibrosis, preservation of antioxidant glutathione, and suppression of neutrophil infiltration.