Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats

The role of oxidative stress in streptozotocin (STZ)-induced toxicity and its prevention by a xanthone glucoside, mangiferin was investigated. To induce diabetes mellitus, adult male Wistar rats were injected STZ intravenously at 55 mg/kg body weight. The effect of mangiferin (10 and 20 mg/kg, i.p., 28 days) was investigated in STZ-induced diabetic male rats. Insulin-treated rats (6 U/kg, i.p., 28 days) served as positive control. Diabetic rats given normal saline served as negative control. Normal rats that neither received STZ nor drugs served as normal control. On day 28, the diabetic rats showed significant increase in serum creatine phosphokinase (CPK) and total glycosylated haemoglobin. Kidney revealed tubular degeneration and decreased levels of superoxide dismutase (SOD) and catalase (CAT) with an elevation of malonaldehyde (MDA). Cardiac SOD, CAT and lipid peroxidation were significantly increased. Histopathological findings revealed cardiac hypertrophy with haemorrhages. Analysis of erythrocyte revealed significantly elevated levels of MDA with insignificant decrease in CAT and SOD. Repeated intraperitoneal injections of mangiferin (10 and 20 mg/kg) and insulin (6 U/kg) controlled STZ-induced lipid peroxidation and significantly protected the animals against cardiac as well as renal damage. From the study, it may be concluded that oxidative stress appears to play a major role in STZ-induced cardiac and renal toxicity as is evident from significant inhibition of antioxidant defence mechanism in renal tissue or a compensatory increase in antioxidant defence mechanism in cardiac tissue. Intraperitoneal administration of mangiferin exhibited significant decrease in glycosylated haemoglobin and CPK levels along with the amelioration of oxidative stress that was comparable to insulin treatment.     

Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.     

Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet

In the present study, we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin, or their combination on renal damage in streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide (LPO) excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after STZ administration. Daily treatment with vitamin E, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals when histopathological evaluation was performed at 4, 8, and 15 weeks (glomerular and mesangial hypertrophy were observed only at 15 weeks). Combined vitamin E and insulin treatment was the most effective at suppressing these renal histopathological changes. These results indicate that combined vitamin E and insulin treatment additively prevents the development and progression of renal damage in diabetic rats. Possible mechanisms for the preventive effect of this combined treatment are discussed.     

Effect of vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats.

Antitumor agents are used as a common therapy against some kinds of cancer. However, as with many agents that have mammalian cell toxicity as a target, physiological adverse effects can occur such as nephrotoxicity and genotoxicity that can be induced in non-tumor cells by generating activated oxygen species, which attack the DNA frequently resulting in oxidative DNA damage. To diminish the undesirable side-effects of therapy and to reduce the levels of oxidative DNA damage, it is recommended for patients to ingest food supplements and vitamins combinations containing substantial amounts of antioxidants. In the present study, we investigated the effects of cisplatin and vitamin C on the renal toxicity and on the oxidative DNA damage. Rats were co-treated with the chemotherapeutic agent cisplatin (5 mg kg(-1) body weight) and dietary doses of vitamin C (50 and 100 mg kg(-1) body weight). Results demonstrated that depending on the treatment protocol, we observed alterations in parameters such as body weight, urinary volume and urinary creatinine, indicating some kidney toxicity. We also observed changes in the urinary levels of 8-OHdG, suggesting possible oxidative DNA damage.     

Crocin attenuates cisplatin-induced renal oxidative stress in rats

Reactive oxygen species (ROS) and oxidative damage are the most important factors in cisplatin-induced acute renal failure. This study examined the protective effects of crocin against cisplatin-induced renal oxidative stress in rat. Animals were divided into five groups (n = 6). Group 1 received normal saline (2 ml/day, i.p.). Group 2 received a single dose of cisplatin (5 mg/kg, i.p.). Groups 3–5 received crocin (100, 200, and 400 mg/kg, i.p., respectively) for four consecutive days beginning 1-h before a single dose of cisplatin (5 mg/kg) on day 1. On day 5, blood samples were drawn and kidneys were removed for histopathological, biochemical and RT-PCR examinations. Twenty four hours urinary chemistries were measured. Blood urea and creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower compared to the cisplatin-treated group. Histopathological studies showed massive damage in the S₃ segment of proximal tubules in cisplatin-treated group but not in crocin-treated groups. Crocin treatment resulted in a significant reduction in malondialdehyde (MDA) concentration and produced a significant elevation in total thiol and glutathione peroxidase concentrations. There was a significant elevation in the mRNA expression of glutathione peroxidase in crocin-treated groups. The results suggest that crocin attenuates cisplatin-induced renal 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.     

Effects of misoprostol on cisplatin-induced renal damage in rats

Cisplatin (CP) is a potent anticancer drug. However, it has side effects on kidney such as nephrotoxicity. Abnormal production of reactive oxygen species (ROS) has been accused in the etiology of CP-induced nephrotoxicity. Several ROS scavengers have been reported to prevent nephrotoxicity after CP administration. In this study, we used prostaglandin E1 (PGE1) analogues misoprostol (MP) to reduce this damage. MP has gained considerable interest as a ROS scavenger. Rats were received a single injection of CP (5 mg/kg, i.p.) with or without MP pretreatment (200 mcg/kg, orally). The renal tissue morphology was investigated by light microscopy. Trunk blood was also obtained to determine lipid peroxidation product malondialdehyde (MDA) and activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT). CP administration increased MDA production and decreased SOD and CAT levels in the kidney tissue when compared to the control group. Morphological damage in CP administrated rats was also severe in the kidney tissue. MP treatment after CP application protected the renal tissues from CP’s side effect. These findings indicate that MP has beneficial effects on CP induced nephrotoxicity in rats.     

Protection of endotoxin-induced oxidative renal tissue damage of rats by vitamin E or/and EGb 761 treatment

The aim of the present study was to evaluate the possible protective effects of vitamin E and EGb 761 treatments, alone or in combination, against oxidative renal tissue damage in experimentally induced endotoxaemic rats. Fifty healthy male Wistar albino rats, weighing 150-250 g and averaging 12 weeks old, were allotted randomly into one of five experimental groups: A (untreated), B (endotoxaemic), C (endotoxaemic + vitamin E treated), D (endotoaxemic + EGb 761 treated) and E (endotoxaemic + vitamin E and EGb 761 treated), each containing ten animals. Group A received only an intraperitoneal (i.p.) injection of 2 ml of normal saline solution and served as the control. Groups B, C, D and E were administrated a single i.p. injection of 0.5 ml of endotoxin solution. In addition, groups C, D and E received i.p. injections of 600 mg kg(-1) body mt. of vitamin E and oral extract of 50 mg kg(-1) body wt. of EGb 761, alone or in combination, immediately after the endotoxin injection. The experiment lasted for 24 h. At the end of the experiment blood and tissue samples were obtained for biochemical and histopathological investigation. Endotoxin injection produced renal damage, increased lipid peroxidation and decreased antioxidant enzyme activity. Vitamin E or/and EGb 761 treatment decreased lipid peroxidation, increased antioxidant enzyme activity and also prevented renal tissue damage in experimentally induced endotoxaemic rats. In conclusion, vitamin E and EGb 761 treatment, alone or in combination, appears to be beneficial in preventing endotoxin-induced oxidative renal tissue damage and therefore shows potential for clinical use.     

大鼠急性肾缺血再灌注时心肌细胞氧化损伤及瑞芬太尼的干预作用

目的观察大鼠急性肾缺血再灌注时心肌细胞氧化损伤以及瑞芬太尼预处理对氧化损伤的干预作用。方法建立大鼠肾缺血再灌注损伤模型。将54只Wistar大鼠随机分为假手术组(Sham组)、缺血再灌注组(I/R组)、瑞芬太尼预处理组(R组)。Sham组只结扎单侧肾脏,另一侧只穿线不结扎;I/R组结扎右侧肾脏,动脉夹夹闭左侧肾蒂45min后开放,于再灌注30min、1、2、3h处死大鼠;R组为缺血前以1μg·kg-1·min-1微泵输注瑞芬太尼30min进行预处理,余同I/R组。分别检测各组大鼠心肌组织超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量及谷胱甘肽过氧物酶(GSH-Px)活力变化。结果I/R组、R组与Sham组相比,心肌组织MDA含量升高,SOD、GSH-Px活力降低,且在1、2、3h时间点,差异均有统计学意义(P<0.05)。R组与I/R组比较,心肌组织MDA含量降低,SOD、GSH-Px的表达增高,且差异有统计学意义(P<0.05)。结论大鼠急性肾缺血再灌注可造成心肌细胞氧化损伤,而瑞芬太尼预处理可起到一定的保护作用。     

beta-glucan protects against burn-induced oxidative organ damage in rats

Thermal injury may lead to systemic inflammatory response, and multiple organ failure. Generation of reactive oxygen radicals and lipid peroxidation play important roles in burn-induced remote organ injury. In the present study, we investigated the putative protective effect of local or systemic beta-glucan treatment on burn-induced remote organ injury. Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce thermal trauma. beta-glucan (3.75 mg/rat locally or 50 mg/kg orally) or saline was administered immediately after the trauma and were repeated twice daily in 48 h groups. Rats were decapitated either 6 or 48 h after burn injury and the skin, lung, liver, ileum and kidney tissues were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase (MPO) activity, while the tumor necrosis factor-alpha (TNF-alpha) levels were measured in serum samples. Skin tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decreases in GSH levels of the liver and intestinal tissues (p<0.01-<0.001), while MDA levels were significantly (p<0.01-p<0.001) increased at post-burn 6 and 48 h. Both local and systemic beta-glucan treatments significantly reversed (p<0.01-p<0.001) the elevations in MDA levels, while reduced GSH levels were reversed back to control levels (p<0.01-p<0.001); and the raised MPO levels were significantly decreased (p<0.05-p<0.001). The results indicate that both systemic and local administration of beta-glucan were effective against burn-induced oxidative tissue damage in the rat. beta-glucans, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, beta-glucans merit consideration as therapeutic agents in the treatment of burn injuries.     

Quillaja saponaria bark saponin protects Wistar rats against ferrous sulphate-induced oxidative and inflammatory liver damage

Context: Saponins from different sources are historically reported in Chinese medicine to possess many beneficial effects. However, insufficient experimental data are available regarding the hepatoprotective potential of Quillaja bark saponin.

Objective: The protective effect of Quillaja saponaria Molina (Quillajaceae) bark triterpenoid saponin against iron-induced hepatotoxicity is compared to the standard N-acetylcysteine in adult male Wistar rats.

Materials and methods: Animals were divided into (six) groups, namely a normal control, an N-acetylcysteine control (300?mg/kg/day, p.o., 10?days), a saponin control (100?mg/kg/day, p.o., for 10?days), a hepatotoxicity control (two doses of ferrous sulphate, 30?mg/kg/day each, i.p., on 9th and 10th day), an N-acetylcysteine plus ferrous sulphate (standard treatment) and a saponin plus ferrous sulphate (test treatment) group. Hepatocyte integrity loss markers (serum ALT, AST, ALP, GGT and LDH), oxidative stress markers (hepatic MDA, GSH and NO_x), dyslipidaemic markers (serum TC and TG) and hepatocyte functioning markers (serum bilirubin and albumin) were assessed.

Results: Quillaja bark saponin decreased iron-induced elevation of ALT (reaching 57% of hepatotoxicity control), AST (66%), ALP (76%), GGT (60%), LDH (54%), MDA (65%), NO_x (77%), TC (70%), TG (54%), and total (54%), direct (54%) and indirect (54%) bilirubin, coupled with increased GSH (219%) and albumin (159%) levels. Histopathological study strongly supported biochemical estimations, while immunohistochemical study showed marked effect on eNOS and iNOS expression.

Conclusions: Quillaja bark saponin has a good hepatoprotective effect. Amelioration of oxidative stress and suppression of NOS expression, with resultant maintenance of hepatocyte integrity and functioning, may explain this beneficial effect.     

Curcumin pretreatment protects against acute acrylonitrile-induced oxidative damage in rats

Acrylonitrile (AN) is widely used in the manufacturing of fibers, plastics and pharmaceuticals. Free radical-mediated lipid peroxidation is implicated in the toxicity of AN. The present study was designed to examine the ability of curcumin, a natural polyphenolic compound, to attenuate acute AN-induced lipid peroxidation in the brain and liver of rats. Male Sprague–Dawley rats were orally administered curcumin at doses of 0 (olive oil control), 50 or 100 mg/kg bodyweight daily for 7 consecutive days. Two hours after the last dose of curcumin, rats received an intraperitoneal injection of 50 mg AN/kg bodyweight. Acute exposure to AN significantly increased the generation of lipid peroxidation products, reflected by high levels of malondialdehyde (MDA) both in the brain and liver. These increases were accompanied by a significant decrease in reduced glutathione (GSH) content and a significant reduction in catalase (CAT) activity in the same tissues. No consistent changes in superoxide dismutase (SOD) activity were observed between the control and AN-treatment groups in both tissues. Pretreatment with curcumin reversed the AN-induced effects, reducing the levels of MDA and enhancing CAT activity and increasing reduced GSH content both in the brain and liver. Furthermore, curcumin effectively prevented AN-induced decrease in cytochrome c oxidase activity in both liver and brain. These results establish that curcumin pretreatment has a beneficial role in mitigating AN-induced oxidative stress both in the brains and livers of exposed rats and these effects are mediated independently of cytochrome P450 2E1 inhibition. Accordingly, curcumin should be considered as a potential safe and effective approach in attenuating the adverse effects produced by AN-related toxicants.     

Protective role of phosphatidylcholine against cisplatin-induced renal toxicity and oxidative stress in rats

Although cisplatin is widely used in the treatment of cancers, clinical use of cisplatin is limited due to its nephrotoxicity. Pathophysiological mechanism of cisplatin-induced renal toxicity is a complex process and has not been fully understand. Reactive oxygen species (ROS) and oxidative stress have been presumed to be involved in this damage process. Phosphatidylcholine (PC) has antioxidant effect and prevents oxidative stress. Therefore, the present study aimed to investigate potential protective effects of PC on cisplatin-induced renal damage in rat. We examined the protective effects of PC on cisplatin-induced renal damage by assessment of serum creatinine, BUN, lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, superoxide dismutase activity and histophathological changes. PC ameliorated cisplatin-induced increases in serum creatinine, urea and oxidative stress. PC also decreased tubular degeneration and hypertrophy of glomeruli. PC may have a protective effect against cisplatin-induced nephrotoxicity in rats via enhancing antioxidant enzyme activity.     

Methiocarb-induced oxidative damage following subacute exposure and the protective effects of vitamin E and taurine in rats

Methiocarb, is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. In this study, we aimed to investigate subacute effects of methiocarb on lipid peroxidation, reduced glutathione (GSH), antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) and histopathological changes in rat tissues. Moreover, we examined the possible protective effects of vitamin E and taurine on methiocarb-induced oxidative damage in rat tissues. Rats were randomly divided into six groups as follows; I-control group; II-methiocarb group; III-vitamin E group; IV-vitamin E + methiocarb group; V-taurine group and VI-taurine + methiocarb group. Methiocarb significantly increased lipid peroxidation in liver and kidney when compared to control groups. Levels of GSH and activities of SOD, CAT and GSH-Px were found to be decreased, while GSH-Rd remained unchanged in rat liver and kidney treated with methiocarb. Pretreatment of vitamin E and taurine resulted in a significant decrease on lipid peroxidation, alleviating effects on GSH and antioxidant enzymes. The degenerative histological changes were less in liver than kidney of rats treated with methiocarb. Pretreatment of vitamin E and taurine showed a protective effect on the histological changes in kidney comparing to the liver of rats treated with methiocarb.     

Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.     

L-carnitine ameliorates oxidative damage due to chronic renal failure in rats

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species. L-Carnitine is a cofactor required for transport of long-chain fatty acids into the mitochondrial matrix. Recent research has shown that some clinical conditions (i.e., anorexia, chronic fatigue, coronary heart disease, diphtheria, hypoglycemia, and male infertility) benefit from exogenous supplementation of L-carnitine. The aim of this study was to examine the role of L-carnitine in protecting the aorta, heart, corpus cavernosum, and kidney tissues against oxidative damage in a rat model of CRF. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or L-carnitine (500 mg/kg, i.p.) for 4 weeks. CRF was evaluated by BUN and serum creatinine measurements. Aorta and corporeal tissues were used for contractility studies or stored along with heart and kidney tissues for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels. Plasma MDA, GSH levels and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were also studied. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls and were partially reversed by L-carnitine treatment. In the CRF group, there were significant increases in tissue MDA with marked reductions in GSH levels in all tissues and plasma compared with controls. In the plasma SOD, CAT and GSH-Px activities were also reduced. All these effects were reversed by L-carnitine as well. The increase in MDA level and the concomitant decrease in GSH level of tissues and plasma and also suppression of the antioxidant enzyme activities in plasma demonstrate that oxidative mechanisms are involved in CRF-induced tissue damage. L-carnitine, possibly via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury and CRF-induced dysfunction of the aorta and corpus cavernosum. These results suggest that L-carnitine supplementation may have some benefit in CRF patients.     

Lack of reversal of oxidative damage in renal tissues of lead acetate‐treated rats

Removal of lead from the environment of man or otherwise, the movement of man from lead‐contaminated areas has been employed as a means of abatement of the toxic effects of lead. Whether toxic effects in already‐exposed individuals subside after lead withdrawal remains unanswered. To understand the reversibility of nephrotoxicity induced by lead acetate, male Wistar rats were orally exposed to 0.25, 0.5, and 1.0 mg/mL of lead acetate for 6 weeks. Activities of glutathione‐s‐transferase, catalase (CAT), superoxide dismutase (SOD) and the concentrations of hydrogen peroxide (H₂O₂), and malondialdehyde increased significantly (p < 0.05) in a dose‐dependent manner, whereas reduced glutathione (GSH) level and glutathione peroxidase activity were significantly reduced. The pattern of alterations in most of the oxidative stress and antioxidant parameters remained similar in rats from the withdrawal period, although CAT and SOD activities reduced, in contrast to their elevation during the exposure period. Serum creatinine levels were significantly elevated in both exposure and withdrawal experiments whereas serum blood urea nitrogen levels were not significantly different from the control in both exposure and withdrawal periods. The histological damage observed include multifocal areas of inflammation, disseminated tubular necrosis, and fatty infiltration of the kidney tubules both at exposure and withdrawal periods. The results suggest that lead acetate‐induced nephrotoxicity by induction of oxidative stress and disruption of antioxidant. The aforementioned alterations were not reversed in the rats left to recover within the time course of study. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1235–1243, 2015.     

Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats

The aim of this study was to investigate the possible protective role of lycopene on cisplatin (CP)-induced spermiotoxicity using quantitative, biochemical and histopathological approaches. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received physiological saline; animals in cisplatin group received only cisplatin; pre-treatment group received a 10-day of lycopene before administration of cisplatin while animals in post-treatment group received a 5-day of lycopene following administration of cisplatin. Cisplatin (7 mg kg(-1)) was intraperitoneally (i.p.) injected as a single dose and lycopene (4 mg kg(-1)) was administered by gavage in corn oil. Traits of reproductive organs; sperm characteristics, testicular histological findings, plasma testosterone levels and the testicular tissue oxidative status were determined. Administration of cisplatin to rats decreased sperm concentration (p < 0.05) and sperm motility (p < 0.001), increased total abnormal sperm rates (p < 0.05) as compared with the control group. While a marked normalization was achieved only in sperm concentration with lycopene in pre-treatment group, significant normalizations were achieved in the sperm concentration, sperm motility, total abnormal sperm rates in post-treatment group. No significant differences in levels of testosterone were observed among all groups. An increase in testes malondialdehyde concentrations (p < 0.05) and glutathione peroxidase activities (p < 0.001) were detected while significant decreases in glutathione levels (p < 0.001) in cisplatin alone group when compared to control group. While pre-treatment with lycopene restoring only malondialdehyde concentrations, its post-treatment caused normalization in both malondialdehyde and glutathione levels when compared with the cisplatin alone group. On the other hand, significant increases were determined in GSH-Px activities in all experimental groups when compared with the control group. Although the mechanism is not clear, the results from this experimental study suggest that the lycopene have a possible protective effect against cisplatin-induced spermiotoxicity, effect of giving lycopene after cisplatin being superior to the giving it before cisplatin.     

Curcumin attenuates gentamicin-induced renal oxidative damage in rats.

The present investigation reports the effect of curcumin, an antioxidant, on gentamicin-induced-renal oxidative damage in rats. Curcumin (200 mg/kg p.o.) was administered for 2 weeks before and 1 week simultaneously with gentamicin (100 mg/kg i.p.). Saline treated rats served as control. Serum creatinine, blood urea (BUN), urinary protein, glucose, urine gamma glutamyl transferase and urine volume increased in rats treated with gentamicin while creatinine clearance decreased compared to controls P<0.001. Renal histological examination revealed tubular necrosis. Curcumin significantly normalized the above parameters. Gentamicin decreased the activities of catalase (CAT), gutathione peroxidase (GSHPx) and the level of glutathione (GSH) but the activity of copper, zinc-superoxide dismutase (Cu, Zn-SOD) was unaltered compared to control. Curcumin attenuated the gentamicin-induced reduction in the activities of CAT, GSHPx and level of GSH by 31%, 55% and 74%, respectively. Curcumin attenuated the gentamicin-induced increases in both plasma malondialdehyde (MDA) and kidney MDA by 57% and 62%, respectively, as well as lipid hydroperoxide (LOOH) formation by 52% and 56% in rat plasma and kidney, respectively. However, Curcumin did not reduce gentamicin-induced formation of LOOH, both in the plasma and kidney, in the presence of exogenous oxidants (1 mM FeSO4, 1 mM ascorbate, 0.2 mM H2O2). Our data indicate that the natural antioxidant curcumin can be a potent protective agent against renal oxidative damage mediated by gentamicin.     

Melatonin protects against renal oxidative stress after obstructive jaundice in rats

The goals of this study were to analyze the renal oxidative status in experimental biliary obstruction and to evaluate the impact of melatonin on renal oxidative stress. Cholestasis was done by double ligature and section of the extra-hepatic biliary duct. Melatonin was injected i.p. (500 microg/kg/day). Malondialdehyde, reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione transferase were determined in the renal tissue. After biliary obstruction, an increase in malondialdehyde (P<0.0001) and a fall in reduced glutathione (P<0.0001) were seen. Moreover, the scavenger enzyme activity had significantly diminished. After melatonin administration, the malondialdehyde fell significantly (P<0.0001), whereas reduced glutathione showed an important increase (P<0.0001) compared with the ligated bile duct group. Experimental bile duct obstruction was associated to an increase of renal oxidative stress. Treatment with melatonin decreased the renal lipid peroxidation, and both the reduced glutathione as well as the scavenger enzyme activity recovered.