Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice

This study investigated the protective effects of pravastatin against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Pravastatin showed significant protection as evidenced by the decrease of elevated serum creatinine (CRE) and blood urea nitrogen (BUN), and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde (MDA) with a concomitant reduction of reduced glutathione (GSH) were inhibited by pravastatin, while the activities of kidney superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) were increased. The over expressions of kidney induced nitric oxide synthase (iNOS) and nitrotyrosine (3-NT) were suppressed by pravastatin. Pravastatin suppressed cisplatin-induced p38 mitogen-activated protein kinase (MAPK) activation in the kidney of mice. These results suggest that pravastatin pre-administration can prevent the nephrotoxicity induced by cisplatin. Pravastatin may exert the protective effect via inhibiting oxidative and nitrosative stress.     

Co-supplementation of single and multi doses of vitamins C and E ameliorates cisplatin-induced acute renal failure in mice

Higher doses of antioxidant vitamins C and E have been proved to be effective against cisplatin-induced nephrotoxicity in animals. However, the possible effective equivalent dose in human was found to be higher than that of the upper tolerable intake level (UL) for these vitamins. Hence, the current study was aimed to evaluate the protective effect of co-supplementation of single and multi doses of vitamins C and E against cisplatin-induced acute renal failure in mice. Single dose of vitamin C (500 mg/kg), vitamin E (500 mg/kg), and vitamin C plus vitamin E (250 mg/kg each) were administered orally 1 h prior to cisplatin (12 mg/kg, i.p) injection, whereas in a multidose study they were administered 1 h prior, and 24 and 48 h after the cisplatin injection. Serum urea and creatinine levels were estimated 72 h after the injection of cisplatin. Renal concentrations of glutathione (GSH) and malondialdehyde (MDA) were also determined. Co-supplementation of vitamins significantly protected the cisplatin-induced increased levels of serum urea, creatinine, renal MDA, and the declined renal GSH level. Administration of single and multi doses of vitamin C plus E (250 mg/kg each) rendered significant nephroprotection. Therefore, accounting for the rare side effect from high intake of vitamins C and E observation of this study indicates that a multidose combination therapy of these vitamins at their lower doses can be effective in protecting the cisplatin-induced renal damage. The protection is partially mediated through the antioxidant effect of the vitamins.     

Effect of metformin against cisplatin induced acute renal injury in rats: A biochemical and histoarchitectural evaluation

Although cisplatin has been a mainstay for cancer therapy, its use is limited mainly because of nephrotoxicity. Accumulating literature suggest the antioxidant and cytoprotective effect of metformin, a first line antidiabetic drug. With this background, we investigated the effect of metformin on the cisplatin induced nephrotoxicity in rats. A single injection of cisplatin (7.5 mg/kg, i.p.) caused marked renal damage, characterized by a significant increase in blood urea nitrogen (BUN), serum creatinine (Cr) and abnormal histo-architecture of kidney. These were accompanied by significant elevation of malondialdehyde (MDA), total reactive oxygen species (tROS) and caspase-3 levels and decreased antioxidant levels. Metformin treatment significantly attenuated the increase in malondialdehyde and tROS generation and restores the decrease in both enzymatic and non-enzymatic antioxidants. However metformin treatment did not prevent the cisplatin induced renal injury as there was no significant difference of renal function parameters (BUN and Cr), kidney histopathology as well as caspase-3 activity between cisplatin per se and metformin plus cisplatin treated rats. Histopathology studies revealed that similar glomerular and tubular pathological architecture in both cisplatin per se and cisplatin plus metformin group. In conclusion, the present study demonstrated that metformin is not an adjuvant drug to treat nephrotoxicity associated with cisplatin therapy.     

Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats

The aim of this study was to investigate the possible protective role of the dietary flavonoid quercetin on cadmium (Cd)-induced nephrotoxicity using biochemical and histopathological approaches. In experimental rats oral administration of CdCl₂ (5 mg/kg) for 4 weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid and creatinine with a significant (p<0.05) decrease in creatinine clearance. Cd also significantly (p<0.05) decreased the levels of urea, uric acid and creatinine in urine. Cd-induced oxidative stress in kidney tissue was indicated by the increased levels of renal lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl content with a significant (p<0.05) decrease in non-enzymatic (total sulphydryl group, reduced glutathione, vitamin C and vitamin E) and enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD)). Moreover the kidneys of Cd-treated rats showed tubular necrosis, degeneration, dilation, desquamation, thickening of basement membrane and luminal cast formation. Quercetin treatment markedly attenuated the Cd-induced biochemical alterations in serum, urine and renal tissue. Quercetin also ameliorated the Cd-induced pathological changes when compared with Cd-alone-treated group. These data indicate that the natural dietary antioxidant quercetin might have protective effect against Cd-induced nephrotoxicity and oxidative stress in rats.     

A Biochemical and Histopathologic Study Showing Protection and Treatment of Gentamicin-Induced Nephrotoxicity in Rabbits Using Vitamin C

Gentamicin and vitamin C have been proposed as nephrotoxic and antioxidant, respectively. This study involved biochemical and histopathologic investigation showing protection and treatment of gentamicin-induced nephrotoxicity in rabbits using vitamin C for 26 days hypothesizing that whether vitamin C would inhibit or decrease the raised serum urea and creatinine levels. This study was conducted on 25 healthy male albino rabbits (average weight 1.5±0.2 kg), classified into 5 groups: group A, B, C, D and E for nephrocurative (study-I) and nephroprotective (study-II) studies. Control group of rabbits (group A) received only the vehicle of gentamicin ampoule. In study-I, gentamicin sulphate (GS 80 mg/kg, i.m.) was administered to group B and C rabbits for ten days, then group C rabbits received vitamin C 250 mg/Kg for remaining 16 days. Group D and E received GS 80 mg/kg and GS 80 mg/kg i.m.-vitamin C 250 mg/kg orally, respectively during whole period (26 days) of study-II. After 26 days, various biochemical parameters, i.e. serum creatinine, blood urea nitrogen (BUN), and serum antioxidant activity, and histopathologic investigations were made. Nephrotoxicity was observed in rabbit groups B, C and D as evident from significant (p<0.05) high levels of serum creatinine and BUN and low serum antioxidant levels as compared to the levels of control group. Decrease in the levels of serum creatinine and BUN along with the increase in serum antioxidant activity was observed after vitamin C treatment in group C. While, renal-protective role of vitamin C was seen in group E as compared to the control. In conclusion, Gentamicin induced nephrotoxicity can be attenuated or treated using vitamin C.     

Effects of co-supplementation of vitamins E and C on gentamicin-induced nephrotoxicity in rat

Gentamicin (GM) is an effective antibiotic against severe gram-negative infections. However it can produce nephrotoxicity in human. Reactive oxygen species (ROS) have been proposed as the causative factors of the renal side effects the drug. This study was performed to investigate the protective role of antioxidant vitamins against GM-mediated nephropathy in an in situ model of isolated rat kidney. Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: group 1 (Control) was perfused with Tyrode solution; group 2 (GM), 200 microg ml(-1) GM was added to the perfusate; group 3 (GM + Vit C), as group 2 with vitamin C added to the drinking water for 3 days (200 mg l(-1)) and to the perfusate (100 mg l(-1)); group 4 (GM + Vit E), as group 2 with vitamin E (100 mg (100 g body weight)(-1), i.m.) injected 12 h before the start of the experiment; group 5 (GM + Vit C + Vit E) as group 2 with vitamin E and C co-administered (concentrations and conditions as in groups 3 and 4). To compare the groups, urinary lactate dehydrogenase (LDH), N-acetyle-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities, inulin clearance (glomerular filtration rate, GFR) and renal tissue glutathione (GSH) content were measured. GM caused a significant nephrotoxicity demonstrated by an increase in urinary LDH, NAG and ALP activities. Reduction in GSH content and a marked decrease in GFR were observed compared to controls. Vitamin C inhibited the GM-induced increase in urinary enzyme activities but did not show a significant effect on the GSH content or GFR. Vitamin E prevented the GM-induced reduction in GSH level without a significant improvement in GFR. Co-administration of vitamins C and E significantly prevented the GM-induced nephrotoxicity demonstrating by preservation of GFR and GSH levels and prevention of increase in urinary enzyme activities. We conclude that co-administration of moderate doses of vitamins C and E has beneficial effects on renal preservation in GM-induced nephrotoxicity.     

γ-Glutamyl Transpeptidase-Deficient Mice Are Resistant to the Nephrotoxic Effects of Cisplatin

We have proposed that the nephrotoxicity of cisplatin, a widely used chemotherapy drug, is the result of the binding of cisplatin to glutathione and the subsequent metabolism of the cisplatin-glutathione complex via a gamma-glutamyl transpeptidase (GGT)-dependent pathway in the proximal tubules. To test the hypothesis that GGT activity is essential for the nephrotoxicity of cisplatin, the effects of cisplatin were examined in wild-type and GGT-deficient mice. Mice were treated with 15 mg cisplatin/kg. Five days after treatment, renal histopathology, blood urea nitrogen levels, serum creatinine, platinum excretion, and platinum accumulation in the kidney were examined. Half the mice were supplemented with N-acetylcysteine, which has been shown to correct low levels of tissue glutathione in GGT-deficient mice. The data show that cisplatin was nephrotoxic in wild-type mice but not in GGT-deficient mice. The wild-type mice, with and without N-acetylcysteine supplementation, had significantly elevated levels of blood urea nitrogen, serum creatinine, and renal tubular necrosis. There was no evidence of nephrotoxicity in the GGT-deficient mice regardless of N-acetyl cysteine supplementation. No differences in platinum excretion were seen comparing wild-type and GGT-deficient mice, nor was there any significant difference in renal platinum accumulation. These data suggest that renal cisplatin toxicity is dependent on GGT activity, and is not correlated with uptake. The results support our hypothesis that the nephrotoxicity of cisplatin is the result of the metabolism of the drug through a GGT-dependent pathway.     

Toxic effects of lambda-cyhalothrin,a synthetic pyrethroid pesticide,on the rat kidney: Involvement of oxidative stress and protective role of ascorbic acid

Lambda-cyhalothrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The objective of this study was to investigate the propensity of lambda-cyhalothrin (LTC) to induce oxidative stress, changes in biochemical parameters and enzyme activities in the kidney of male rats and its possible attenuation by Vitamin C (vit C). Renal function, histopathology, tissue malondialdehyde (MDA), protein carbonyl (PCO) levels, antioxidant enzyme activities and reduced glutathione (GSH) levels were evaluated. Exposure of rats to lambda-cyhalothrin, during 3 weeks, caused a significant increase in kidney MDA and protein carbonyl levels (p<0.01) as compared to controls. Co-administration of vitamin C was effective in reducing MDA and PCO levels. The kidney of LTC-treated rats exhibited severe vacuolations, cells infiltration and widened tubular lumen. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were significantly decreased due to lambda-cyhalothrin exposure. Co-administration of vitamin C ameliorated the increase in enzymatic activities of aminotransferases (AST and ALT), lactate dehydrogenase (LDH), creatinine and urea levels and improved the antioxidant status.These data indicated the protective role of ascorbic acid against lambda-cyhalothrin-induced nephrotoxicity and suggested a significant contribution of its antioxidant property to these beneficial effects.     

Prevention of cisplatin induced nephrotoxicity by terpenes isolated from Ganoderma lucidum occurring in Southern Parts of India

Investigations were carried out to determine the protective effect of terpenes isolated from the fruiting bodies of Ganoderma lucidum (Fr) P.Karst against nephrotoxicity caused by the cisplatin, in mice. Intraperitoneal administration of cisplatin (16 mg/kg body wt) resulted in significant nephrotoxicity in mice. Serum urea, creatinine and ALP levels were drastically elevated indicating severe nephrotoxicity . The renal antioxidant defense system such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and concentration of reduced glutathione (GSH) were depleted by cisplatin injection. The oral administration of terpenes at a dose of 100 mg/kg body weight prevented increase in urea, creatinine levels and ALP activity and also maintained the renal antioxidant defense. The Ganoderma terpenes also imparted protection against cisplatin induced renal tissue lipid peroxidation. The results indicated that the total terpenes isolated from G. lucidum possessed significant in vivo antioxidant activity and rendered protection against cisplatin induced nephrotoxicity. The results suggest the potential therapeutic use of Ganoderma terpenes to prevent nephrotoxicity caused during chemotherapy using cisplatin.     

Aqueous extract of Terminalia arjuna prevents cyclosporine-induced renal disorders

Cyclosporine (CsA), a powerful immunosuppressant, had a significant impact on transplantation medicine, and exposure to this chemical is known to induce oxidative stress and causes renal injury by the formation of free radicals. Acute and chronic renal damage are very common pathophysiologic disturbances caused by CsA. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Terminalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CsA-induced oxidative stress and resultant dysfunction in the rat kidney. Animals were treated with the aqueous extract of TA (100 mg/kg body weight (b.wt)) and then treated with CsA (25 mg/kg b.wt) in olive oil for 14 days. The level of urea, uric acid, and creatinine was determined from serum sample. The enzymes, namely, alkaline phosphatase (ALP), acid phosphatase (ACP), aspartate transaminase (AST), and alanine transaminase (ALT), and enzymic indices of membrane integrity such as Na⁺K⁺ATPase, Ca²⁺ATPase, and Mg²⁺ATPases were estimated in the tissue of all study groups. Antioxidant status in kidney tissues was estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione transferase (GST) and the levels of reduced glutathione, vitamin E, and vitamin C. In addition, the kidney phospholipids, cholesterol, triglycerides, and free fatty acids were determined in the tissue. Results showed that CsA caused a marked increase in the levels of urea, uric acid, and creatinine in serum and decreases the levels of ALP, ACP, AST, ALT, Na⁺K⁺ATPase, Ca²⁺ATPase, Mg²⁺ATPases, SOD, CAT, glutathione reductase, GST, GPx, vitamin E, and vitamin C whereas cholesterol, triglycerides, free fatty acid, and phospholipid levels were found to be increased in the kidney tissue homogenates of CsA-treated rats. Aqueous extract of TA successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C. Our study demonstrated that the aqueous extract of the bark of TA could protect the kidney tissues against CsA-induced oxidative stress probably by increasing antioxidative defense activities.     

Vitamin B6 dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in rat model of nephrotoxicity: the histopathologic and biochemical findings

Despite its significant anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant-protecting effects of vitamin B₆ in the kidney, with a view on the vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of cisplatin. Hence, 50 male Sprague–Dawley rats were randomly assigned in one of five groups of the study to receive a corresponding dose of either normal saline, vitamin B₆ (200 mg/kg/bw; i.m.) or cisplatin alone (7 mg/kg/bw; i.m.), or in combination with vitamin B₆ at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of renal failure. Daily administration of cisplatin at a dose of 7 mg/kg/bw resulted in a significant increase in local and systemic oxidative stress of the kidney and a decrease in glomerular function as a result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of the study, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B₆ at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to the low-dose rats and controls. In high-dose animals, the normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that the antioxidant property of vitamin B₆ consistently increases with the dose intensity. The present study also provided evidence that high dose of vitamin B₆ prevented both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.     

Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and alpha-tocopherol

BACKGROUND: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, at effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals. METHODS: Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or alpha-tocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue. RESULTS: Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation. CONCLUSION: These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity.     

Arjunolic acid attenuates arsenic-induced nephrotoxicity.

Arsenic is highly toxic naturally occurring element that affects numerous organ systems in humans. Present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced nephrotoxicity in mouse model. For this study, NaAsO(2) was chosen as the source of arsenic. Oral administration of NaAsO(2) at a dose of 10mg/kg body weight for 2 days caused significant accumulation of arsenic in renal tissues as well as altered the activities of serum markers, urea nitrogen (UN) and creatinine, antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx), level of cellular metabolites, reduced glutathione (GSH), oxidized glutathione (GSSG) and total thiols, level of lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20mg/kg body weight for 4 days almost normalized above indices. Histological studies also indicated preventive role of AA against NaAsO(2)-induced nephrotoxicity. The radical scavenging activity and in vivo antioxidant power of AA were determined from its DPPH radical scavenging ability and ferric reducing/antioxidant power (FRAP), respectively. A well-known antioxidant, vitamin C was used as positive control throughout the study. Combining all, results suggest that arsenic could cause kidney damage by inducing oxidative stress in mice and that could be prevented by AA.     

不同剂量补肾方药对顺铂所致大鼠肾毒性的影响

目的：观察不同剂量中药对顺铂(DDP)所致大鼠肾毒性的影响。方法：经尾静脉注射DDP诱发大鼠肾毒性,同时给大鼠灌服不同剂量益气补肾中药,观察大鼠肾组织在光镜及电镜下形态的改变,并检测大鼠血清尿素氮(BUN)的含量。结果：中剂量益气补肾中药能明显减轻DDP所致大鼠的肾损害,并使BUN含量明显降低。结论：适当剂量的益气补肾中药是拮抗DDP引起的肾毒性的有效药物。     

鹿茸水提物减轻顺铂所致的小鼠肾损伤

目的:探讨梅花鹿二杠茸和三岔茸水提物对顺铂(CDDP)所致小鼠肾损伤的影响。方法:采用灌胃给药方式,用顺铂(15 mg/kg)诱导小鼠肾损伤模型,测定小鼠肾脏指数(KI)、血清肌酐(SCr)、血尿素氮(BUN)、肾脏组织中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,并对肾脏组织进行HE染色,观察肾脏病理学变化,研究梅花鹿二杠茸和三岔茸的水提物各剂量对小鼠肾损伤的影响。结果:与顺铂组相比,各剂量鹿茸水提物可显著降低CDDP诱导肾损伤小鼠SCr、BUN水平及肾脏MDA含量,提高SOD和GSH-Px的活性(P0.05);明显改善肾组织病理学形态,减轻CDDP对肾小管上皮细胞的损伤程度,且同等浓度下,与三岔茸相比,二杠茸水提物能更好地改善肾功能及减轻病理损伤。结论:鹿茸水提物减轻顺铂引起的小鼠肾损伤,其作用机制可能与鹿茸水提物增强小鼠肾脏组织的抗氧化能力有关。     

Methionine-supplemented diet augments hepatotoxicity and prooxidant status in chronically ethanol-treated rats

The purpose of this study was to investigate whether high methionine (HM) diet may influence the development of ethanol-induced hepatotoxicity and prooxidant–antioxidant balance in the liver. Rats received drinking water containing ethanol (20% v/v) and/or methionine supplemented diet (2% w/w) for 75 days. Although prooxidant–antioxidant balance did not change in the liver of rats in HM group, ethanol treatment was observed to increase plasma transaminase activities, and malondialdehyde (MDA) and protein carbonyl (PC) levels, but not glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver of rats as compared to controls. However, ethanol plus HM diet caused further increases in plasma transaminase activities and hepatic MDA and PC levels. In addition, SOD, GSH-Px and GST activities were observed to decrease, but GSH, vitamin E and vitamin C levels remained unchanged in the liver as compared to ethanol, HM and control groups. Our results show that HM diet may augment hepatotoxicity and oxidative stress in the liver of chronically ethanol-treated rats.     

Efficacy of vitamin E and selenium for the prevention of intra-abdominal adhesions in rats: uterine horn models

OBJECTIVE:

This study compares the efficacies of vitamin E and selenium, both individually and in combination, for the prevention of postoperative intra-abdominal adhesions in rats.

METHODS:

Forty-seven female rats were divided into five groups. The sham animals (S group, n = 7) were given only laparotomies and intraperitoneally received 0.9% NaCl (2 ml). In the 40 other rats, abrasions of the left uterine horn were performed, followed by intraperitoneal administration of either 2 ml 0.9% NaCl (C group), 10 mg vitamin E (vitamin E group), 0.2 mg/kg selenium (Se group) or 10 mg vitamin E with 0.2 mg/kg selenium (vitamin E + Se group), with 10 animals in each treatment group.

RESULTS:

Adhesion formation was significantly reduced in animals in the Se and vitamin E + Se groups (p<0.05). Tissue catalase and glutathione peroxidase activities did not significantly differ between the groups. However, catalase and glutathione peroxidase activities and reduced glutathione levels were slightly increased in the vitamin E, Se and vitamin E + Se groups. In the vitamin E group, malondialdehyde concentrations were significantly lower than in the C group (p<0.05), but no significant differences were present among the S, C, Se and vitamin E + Se groups. Levels of nitric oxide were significantly higher in the C group than in the other groups (p<0.01).

CONCLUSION:

Intraperitoneal administration of selenium or combined vitamin E and selenium appears to be effective in preventing intra-abdominal adhesion formation in rat models through the reduction of lipid peroxidation products.     

Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.     

血清胱抑素C、叶酸、维生素B12在慢性肾脏病早期肾损伤中的应用价值

目的 探讨血清胱抑素C(Cys-C),叶酸(FA)、维生素B12(Vit B12)在慢性肾脏病早期肾损伤中的应用价值.方法 选择2014年3月至2016年8月在我院就诊的慢性肾脏病患者167例作为研究对象,按照慢性肾脏病的分期分为五组:第1期组(A组,32例)、第2期组(B组,32例)、第3期组(C组,33例)、第4期组(D组,34例)、第5期组(E组,36例),选择同期体检健康志愿者30例作为健康对照组,采用胶乳免疫比浊法测定血清Cys-C,电化学发光法测定血清FA和VitB12,尿素酶-谷氨脱氢酶法测定血清尿素(Urea),苦味酸法测定血清肌酐(Scr)含量水平.结果 A组各指标测定结果与对照组比较差异无统计学意义(P＞0.05);B组Scr、Urea与对照组及A组比较差异也无统计学意义(P＞0.05),而血清Cys-C高于对照组和A组(P＜0.05);C组、D组和E组各指标测定结果与对照组及A组比较差异均有统计学意义(P＜0.05).ROC曲线显示,Cys-C、Urea、FA、Vit B12、Scr的AUC及95％ CI分别为:0.697 (0.668 ～0.887)、0.538(0.491～0.792)、0.502(0.504～0.822)、0.481(0.532 ～0.865)、0.457(0.484 ～0.775).结论 血清胱抑素C、叶酸和维生素B12检测有助于早期肾功能损伤的判断,对控制慢性肾脏病发展有重要的临床意义.     

Vitamin C dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in adult Swiss albino rats: a histopathologic and biochemical study

Nephrotoxicity is usually thought of as a common invariable consequence of hemodynamic toxicity whose effects, including oliguria and dysuria, has largely limited the clinical use of cisplatin. In this study, we investigated the protective effects of low and high dose of vitamin C against cisplatin-induced rat nephrotoxicity. Hence, 50 adult male Swiss albino rats were randomly divided into five equal groups to receive a corresponding dose of either normal saline as control, vitamin C (600 mg/kg/BW, i.v.), or cisplatin alone (7 mg/kg/BW, i.p.) or in combination with vitamin C at low dose (200 mg/kg/BW, i.v.) and high dose (600 mg/kg/BW, i.v.) for 9 days. Daily administration of cisplatin at a dose of 7 mg/kg/BW resulted in a significant increase in oxidative stress in renal tissues and plasma and a concomitant decrease in the creatinine clearance and renal blood flow as a result of early hemodynamic toxicity. Histopathological examination revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of experiment. Further biochemical studies showed protecting effects of supplemented vitamin C at a high dose, illustrated by slowdown in the urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and the ATPase activity up to 50 % when compared to controls and rats receiving low-dose. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant property of vitamin C increases with dose, and, therefore, high dose of vitamin C prevents both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.