共查询到20条相似文献,搜索用时 31 毫秒
1.
The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day(-1)), oral doses of spironolactone (20.0 mg kg day(-1)) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P<0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four- and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spironolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spironolactone significantly (P<0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit. 相似文献
2.
《General pharmacology》1994,25(6):1249-1252
1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg for 6 days. Treated animals demonstrated a typical pattern of nephrotoxicity characterized by increased serum creatinine and urea concentrations, and by necrosis of proxinal tubular epithelium.2. Pretreatment of rats with iron (Fe3+) at daily i.m. doses of 2, 4 and 8 mg/kg for 14 days, with gentamicin given during the last 6 days of treatment, significantly potentiated the gentamicin-induced increases in creatinine and urea concentrations and exacerbated renal histological damage.3. Gentamicin significantly increased serum Fe3+ concentration in rats treated with Fe3+ and gentamicin, compared to Fe3+-treated rats.4. The Fe3+ antidote deferoxamine (100 mg/kg, i.m.) given with gentamicin was ineffective in antagonizing the potentiating effect of Fe3+ on gentamicine-induced nephrotoxicity.5. Ascorbic acid (50 mg/kg, i.m. for 14 days) was ineffective in altering the nephrotoxicity of gentamincin (80 mg/kg) given during the last 6 days of treatment. At a dose of 100 mg/kg for 14 days, ascorbic acid significantly reduced gentamicin-induced increases in creatinine and urea levels, and ameliorated proximal tubular damage. However, at a dose of 200 mg/kg, ascorbic acid exacerbated gentamicin-induced increases in creatinine and urea levels and increased the severity of the histological damage. 相似文献
3.
B. H. Ali A. A. Abdel Gayoum A. A. Bashir 《Basic & clinical pharmacology & toxicology》1992,70(6):419-423
Abstract: The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose-dependent proximal renal tubular necrosis. Seven days after withdrawal of gentamicin, the degree of necrosis was less marked, and 14 days after drug withdrawal, renal histology was apparently normal. 相似文献
4.
《Pharmacological research》2003,48(6):637-642
The aim of this study was to investigate the effects of manganese chloride on gentamicin-induced nephrotoxicity in rats. Thirty-six adult Wistar Albino rats were divided into six equal groups. They were injected with gentamicin sulfate (100 mg kg−1per day i.p.) and manganese chloride (2 or 20 mg kg−1 per day i.p.) and gentamicin together with manganese chloride for 6 days. The animals were killed 24 h after the last injection. Nephrotoxicity was biochemically and histopathologically evaluated. The concentrations of creatinine, urea, sodium and potassium in plasma, malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and catalase (CAT) activities in kidney tissue were determined. Administration of gentamicin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. A significant increase in kidney MDA and a decrease in GSH concentrations were observed in gentamicin-treated rats. No change was observed in the activities of GSH-Px and CAT in rats treated with gentamicin alone. Administration of the low dose of manganese (Mn2+) produced amelioration in biochemical indices of nephrotoxicity in plasma and kidney tissue when compared to gentamicin group. The histological signs of renal proximal tubules followed a similar pattern. The high dose of Mn2+ (20 mg kg−1) caused an opposite effect on nephrotoxicity induced by gentamicin, causing exacerbation in the tubular necrosis. The results suggest that low dose of Mn2+ may have an antioxidant effect in kidneys of gentamicin administrated rats, but its high doses had no beneficial effect. 相似文献
5.
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. 相似文献
6.
Vijayan FP Rani VK Vineesh VR Sudha KS Michael MM Padikkala J 《Journal of basic and clinical physiology and pharmacology》2007,18(2):101-114
The aim of the present investigation was to evaluate the protective effect of a 70% methanolic leaf extract of Cyclea peltata Lam on cisplatin-induced renal toxicity. The concentration of creatinine, urea, sodium, and potassium in serum and levels of malonyldyaldehyde (MDA), glutathione (GSH), as well as gluathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities were determined in kidney tissue. The marked cisplatin-induced renal damage, characterized by a significant increase in creatinine and urea levels, decreased in extract-treated group, whereas sodium and potassium levels did not change significantly. C. peltata Lam extract significantly changed the increased MDA level and decreased GSH levels found in rats treated with cisplatin alone. The reduced activities of GSH-Px, SOD, and CAT in groups treated with cisplatin alone were significantly increased by the extract. The protective effect was greater in the post-treated than in the pre-treated group of animals. The results indicate that the post-treatment of C. peltata Lam extract might effectively ameliorate the oxidative stress parameters observed in cisplatin induced renal toxicity and could be used as a natural antioxidant against cisplatin-induced oxidative stress. 相似文献
7.
Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats 总被引:4,自引:0,他引:4
Parlakpinar H Tasdemir S Polat A Bay-Karabulut A Vardi N Ucar M Acet A 《Toxicology》2005,207(2):169-177
The toxicity of gentamicin (GEN) in the kidney seems to relate to the generation of reactive oxygen species (ROS). Caffeic acid phenethyl ester (CAPE) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. It has been proposed that antioxidant maintain the concentration of reduced glutathione (GSH) may restore the cellular defense mechanisms and block lipid peroxidation thus protect against the toxicity of wide variety of nephrotoxic chemicals. We investigated the effects of CAPE on GEN-induced changes in renal malondialdehyde (MDA), a lipid peroxidation product, nitric oxide (NO) generation, superoxide dismutase (SOD), catalase (CAT) activities, GSH content, blood urea nitrogen (BUN) and serum creatinine (Cr) levels. Morphological changes in the kidney were also examined. A total of 32 rats were equally divided into four groups which were: (1) control, (2) injected with intraperitoneally (i.p.) GEN, (3) injected with i.p. GEN+CAPE and (4) injected with i.p. CAPE. GEN administration to control rats increased renal MDA and NO generation but decreased SOD and CAT activities, and GSH content. CAPE administration with GEN injections caused significantly decreased MDA, NO generation and increased SOD, CAT activities and GSH content when compared with GEN alone. Serum level of BUN and Cr significantly increased as a result of nephrotoxicity. CAPE also, significantly decreased serum BUN and Cr levels. Morphological changes in the kidney due to GEN, including tubular necrosis, were evaluated qualitatively. In addition, CAPE reduced the degree of kidney tissue damage induced by GEN. Both biochemical findings and histopathological evidence showed that administration of CAPE reduced the GEN-induced kidney damage. Our results indicated that CAPE 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. Thus, CAPE could be effectively combined with GEN treatment. 相似文献
8.
《General pharmacology》1994,25(6):1185-1189
1. The nephrotoxicity of gentamicin is well known. However, little information is available regarding the combined effects of gentamicin plus co-trimoxazole (sulfamethoxazole-trimethoprim). Therefore, Wistar rats were treated daily with 100 mg/kg gentamicin or 100 mg/kg gentamicin plus 30 mg/kg trimethoprim-150 mg/kg sulfamethoxazole for 14 days.2. Serum biochemical parameters were measured on days 0, 8 and 15, and histopathological examinations of kidneys were performed on day 15, one day following end of treatment. Gentamicin treated rats exhibited a 63% increase in blood urea nitrogen (BUN), a 124% increase in uric acid, and a 63% decrease in serum potassium levels on day 15.3. The combination of gentamicin plus co-trimoxazole partially ameliorated these effects. With the three drug combination no change occurred in BUN, and only a 30% decrease occurred in serum potassium levels.4. While serum creatinine levels significantly increased following gentamicin, the co-administration of co-trimoxazole resulted in a significant decrease (30%) in creatinine. Histopathological examinations of kidneys suggested a lower degree of nephrotoxicity in rats treated with gentamicin plus co-trimoxazole as compared to animals treated with gentamicin alone.5. The results support the importance of monitoring serum biochemical parameters when treating with gentamicin or gentamicin plus co-trimoxazole. 相似文献
9.
Nephrotoxicity of gentamicin (GM) has been suggested to be mediated by the generation of reduced oxygen metabolites. The present study investigated the possible protective role of the free radical scavenger dimethyl sulfoxide (DMSO) on some indices of GM nephrotoxicity in rats. The antibiotic was injected intramuscularly (i.m.) at a dose of 100 mg/kg for six consecutive days, either with or without treatment with DMSO (12.5%, 25% or 50% in saline) at an intraperitoneal (i.p.) dose of 2 ml/kg 4 days before GM, and concomitantly with GM treatment thereafter. DMSO (25% in saline) was also given as above to rats treated with GM at i.m. doses of 25, 50 or 100 mg/kg for six consecutive days. GM caused dose-dependent significant increases in the concentrations of urea and creatinine in plasma, and in thiobarbituric acid reactive substances (TBARS) level in the kidney cortex and also caused significant decreases in the concentrations of reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In GM-treated rats, DMSO dose-dependently lowered the elevated plasma urea and creatinine concentrations, and the rise in cortical TBARS. It also restored the levels of GSH and SOD activity to near normal. DMSO (25%) was effective in completely preventing the development of signs of nephrotoxicity of G (50 mg/kg). Treatment of the rats with DMSO alone, at any of the above doses, did not alter significantly any of the renal or hepatic function tests studied, and did not appear to adversely affect the kidney or liver histology. However, the efficacy and safety of DMSO require further studies. It is suggested that DMSO has potential protective effect against GM nephrotoxicity in rats. 相似文献
10.
Diltiazem enhances gentamicin nephrotoxicity in rats 总被引:1,自引:0,他引:1
A Gomez F Martos R Garcia B Perez F Sanchez de la Cuesta 《Pharmacology & toxicology》1989,64(2):190-192
The effect of the calcium antagonist, diltiazem, was examined in gentamicin-induced nephrotoxicity states in rats. Animals were injected for 5 days with diltiazem intraperitoneally (40 mg/kg/day), or gentamicin subcutaneously (100 mg/kg/day) or simultaneously with both preparations using the same doses. At the time of sacrifice, the urea and creatinine clearances, as well as urine osmolality were determined and the renal tissues were processed for examination by light microscopy. Gentamicin-injected rats demonstrated the typical pattern of aminoglycoside nephrotoxicity characterized by poliuric renal failure and necrosis of the proximal tubular epithelium. Rats injected with diltiazem revealed only mild depression of urine osmolality. There was no elevation of blood urea nitrogen and serum creatinine or depression of urea and creatinine clearances, and no focal tubular cell necrosis was detected. However, concomitant administration of both compounds considerably increased nephrotoxicity by according both histological indications and renal function measurements. Thus, we conclude that the combination of diltiazem and gentamicin must be used carefully in human clinical practice. 相似文献
11.
The effects of gemcitabine (dFdC) on the lipid peroxidation and kidney histopathology in the nephrotoxicity of an antitumour drug cisplatin (CDDP) were studied in rats. dFdC was administered intraperitoneally (i.p.) at single doses of 90 mgkg(-1) while CDDP was administered i.p. at single doses of 6 mgkg(-1). Both drugs were injected either alone or sequentially in combination. In one case, CDDP preceded dFdC by 4 h and 24 h and in the other case, dFdC preceded CDDP by 4 h and 24 h. Seven days after CDDP administration, the nephrotoxicity was manifested biochemically by elevation of serum creatinine, blood urea nitrogen and an increase in the kidney weight as a percentage of total body weight. In addition, marked decreases in serum albumin and calcium levels were observed. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde (MDA) production level and kidney glutathione (GSH) content, which were increased and depleted, respectively. Administration of dFdC 4 h and 24 h after CDDP administration did not significantly change the indices of CDDP-induced nephrotoxicity or the kidney platinum concentration levels in comparison with those animals treated with CDDP alone. On the contrary, administration of dFdC 4 h and 24 h prior to CDDP administration significantly aggravated CDDP-induced nephrotoxicity which was manifested by severe increases in the serum creatinine and blood urea nitrogen levels as well as kidney weight as a percentage of total body weight. In addition, kidney tissue showed severe GSH depletion and increases in the MDA production and platinum concentration levels. Moreover, treatment of rats with dFdC 24 h prior to CDDP resulted in much more aggravation of CDDP-induced nephrotoxicity in comparison with those animals treated with dFdC 4 h prior to CDDP. Histopathological examination demonstrated tubular atrophy, tubular necrosis and drug-induced nuclear changes in the CDDP-treated group. However, pretreatment of rats with dFdC 4 h and 24 h prior to CDDP revealed extensive interstitial nephritis, renal tubular atrophy and tubular necrosis with 'sloughing off' of the lining cells, especially with those rats treated with dFdC 24 h prior to CDDP. These results might suggest that administration of dFdC prior to CDDP enhanced the lipid peroxidation in kidney tissue and aggravated CDDP-induced nephrotoxicity. 相似文献
12.
淫羊藿提取液对庆大霉素急性肾损伤的影响 总被引:7,自引:0,他引:7
目的:观察淫羊藿提取兴对庆大霉素致大鼠急性肾毒性的作用。方法:测定在鼠血肌酐、尿素氮的浓度有肾皮质脂质过氧化终产物丙二醛和谷胱甘肽的含量,分析淫羊藿提取液对大鼠肾损伤的有效作用。结果:浮羊藿提取液可降低血肌酐和尿素氮水平的升高,抑制肾皮质过氧化物的产生及减轻谷胱甘肽的耗竭。结论:淫羊藿提取液对庆大霉素所致肾扣伤具保护作用,其机制可能与抗脂质过氧化作用有关。 相似文献
13.
Abdulhakeem A Al-Majed Adel M Mostafa Ammar C Al-Rikabi Othman A Al-Shabanah 《Pharmacological research》2002,46(5):445-451
Arabic gum (AG) is a complex polysaccharide used as suspending agent. It has been widely used by eastern folk medicine practitioners as a restorative agent and is thought to be an excellent curative for renal failure patients. We therefore tested these folkloric claims using a rat model of gentamicin (GM)-induced nephrotoxicity. AG (7.5g 100ml(-1), in drinking water) was administered orally for 8 days concurrently with GM (80mgkg(-1) per day, i.p.). Estimation of urine volume, serum creatinine and urea concentrations, kidney tissue malondialdehyde (MDA) contents and glutathione (GSH) were carried out after the last dose of GM. Kidneys were also examined for histological changes. GM caused a marked nephrotoxicity as evidenced by significant increases in urine volume (295%), serum creatinine (318%) and urea (258%) and a significant decrease in creatinine clearance (Ccr) (26%). Treatment with AG protected the rats from GM-induced nephrotoxicity as evident by normalisation of these parameters. In addition there was about 187% increase in kidney tissue MDA contents above the control with GM treatment. AG totally prevented the GM-induced rise in kidney tissue contents of MDA. Kidney histology of the tissue from GM-treated rats showed necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis. Whereas it was very much comparable to control when AG was co-administered with GM. In conclusion, AG protected the rats from GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation. 相似文献
14.
?brahim Ba?han Perihan Ba?han Mehmet Ata Se?ilmi? Ergin ?ingirik 《Indian journal of pharmacology》2014,46(6):608-612
Introduction:
L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats.Materials and Methods:
Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique.Results:
Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination.Conclusion:
Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in this protective effect.KEY WORDS: D-arginine, gentamicin, HPLC, L-arginine, nephrotoxicity 相似文献15.
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. 相似文献
16.
Beneficial effect of shallot (Allium ascalonicum L.) extract on cyclosporine nephrotoxicity in rats.
The clinical use of an immunosuppressive cyclosporine A (CsA) is limited by its serious nephrotoxic effect. Evidences have suggested the role of oxidative stress in its pathogenesis. Shallot (Allium ascalonicum L.) has recently been shown to possess antioxidative and free radical scavenging abilities. The present study was undertaken to investigate the possible beneficial effect of shallot extract on renal injury caused by CsA. Male Wistar rats were treated orally with vehicle, CsA (25 mg/kg), shallot extract (1 g/kg), and CsA plus shallot extract for 21 days. Renal function, histopathology, tissue malondialdehyde (MDA) and glutathione (GSH) levels were evaluated 24 h after the last treatment. CsA-induced nephrotoxicity was evidenced by increased blood urea nitrogen and serum creatinine, but decreased urea and creatinine clearance. The kidney of CsA treated rats exhibited severe vacuolations and tubular necrosis. CsA also induced oxidative stress, as indicated by increased renal MDA and reduced GSH concentrations. Administration of shallot extract along with CsA counteracted the deleterious effects of CsA on renal dysfunction, oxidative stress markers, and morphological changes. These data indicate the protective potential of shallot extract against CsA nephrotoxicity and suggest a significant contribution of its antioxidant property to this beneficial effect. 相似文献
17.
Rajesh A. Maheshwari R. Balaraman Ashim K. Sen A. K. Seth 《Indian journal of pharmacology》2014,46(6):627-632
Objectives:
This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with metformin on streptozotocin (STZ)-nicotinamide-induced diabetic nephropathy (DN).Materials and Methods:
Type 2 diabetes in rats was induced with STZ-nicotinamide. The diabetic rats were treated with coenzyme Q10 (10 mg/kg, p.o.) alone or coenzyme Q10 + metformin. Various parameters of renal function tests such as serum creatinine, urea, uric acid, and markers of oxidative stress such as renal malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) activity, transforming growth factor-β (TGF-β), and nitrite content were estimated in renal tissues. All treated animal were subjected to histopathological changes of kidney.Result:
Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum urea, serum creatinine, uric acid. In addition, STZ-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and glutathione (GSH) level. Moreover, TNF-α, MPO activity, TGF-β, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-α, MPO activity, TGF-β and nitrite content along with histopathological changes.Conclusions:
This finding suggests that the treatment with coenzyme Q10 or metformin showed significant renoprotective effect against STZ-nicotinamide-induced DN. However, concomitant administration of both showed a better renoprotective effect than coenzyme Q10 or metformin alone treatment.KEY WORDS: Coenzyme Q10, diabetic nephropathy, metformin, transforming growth factor-β, tumor necrosis factor-α 相似文献18.
Guz G Demirogullari B Ulusu NN Dogu C Demirtola A Kavutcu M Omeroglu S Stefek M Karasu C 《Clinical and experimental pharmacology & physiology》2007,34(3):210-216
1. Ischaemia-reperfusion (I/R) injury, one of the main causes of acute renal failure, still needs satisfactory treatment for routine clinical application. Stobadine, a novel synthetic pyridoindole anti-oxidant, has the ability to reduce tissue injury induced by mechanisms involving reactive oxygen species during I/R. The aim of the present study was to determine the effects of stobadine on renal I/R injury. 2. Forty male Wistar rats were randomly divided into four groups as follows: sham, I/R, stobadine treated and I/R + stobadine treated. Stobadine (2 mg/kg, i.v.) was given intravenously to two groups of rats. The stobadine-treated group was treated with stobadine following sham operation before the abdominal wall was closed, whereas the I/R + stobadine group received stobadine at the beginning of reperfusion. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to assess: (i) serum levels of blood urea nitrogen and creatinine; (ii) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione peroxidase (GPx); (iii) renal morphology; and (iv) immunohistochemical staining for P-selectin. 3. Stobadine was able to significantly attenuate the renal dysfunction as a result of renal I/R injury. Ischaemia-reperfusion resulted in a significant increase in serum and kidney MDA levels and a decrease in serum and kidney GSH. Stobadine treatment at the beginning of reperfusion attenuated both the increased MDA levels and decreased GSH secondary to I/R injury. In addition, the decreased G-6PD activity observed after I/R was significantly attenuated by stobadine treatment. Stobadine did not alter 6-PGD activity after I/R. Neither GR nor GPx activity was significantly changed in the I/R alone or the I/R + stobadine groups compared with the sham group. In addition, stobadine decreased the morphological deterioration and high P-selectin immunoreactivity secondary to renal I/R injury. 4. A pyridoindole anti-oxidant, stobadine exerts a renal protective effect in renal I/R injury, which is probably due to its radical-scavenging and anti-oxidant activities. 相似文献
19.
Gentamicin is an antibiotic that is widely used against serious and life-threatening gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Oxidative stress and nitrosative stress are reported to play important role in gentamicin nephrotoxicity. In the present study we investigated whether ebselen, an inhibitor of oxidative stress and nitrosative stress prevents or reduces gentamicin-induced renal damage in the rat. For this purpose male Wistar rats were divided into five groups and treated as follows. Group 1 (control group): dimethyl sulphoxide, intraperitoneally, Group 2: Gentamicin 100 mg/kg b.wt. subcutaneously, Group 3: 5 mg/g b.wt. ebselen intraperitoneally, Group 4: 2.5 mg/kg b.wt. ebselen followed by 100 mg/kg b.wt. gentamicin subcutaneously one hour later, and Group 5: 5 mg/kg b.wt. of ebselen followed by 100 mg/kg b.wt. gentamicin one hour later for four consecutive days. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as reduced glutathione, malondialdehyde, and activities of superoxide dismutase and glutathione peroxidase were measured in the kidney. Serum nitrite and nitrate were measured as indicators of nitrosative stress. Treatment of rats with gentamicin resulted in statistically significant reduction in reduced glutathione levels (51%) and the activities of antioxidant enzymes superoxide dismutase (56%) and glutathione peroxidase (39%) as compared with the controls in the kidneys. Renal malondialdehyde level was increased significantly (43%) as compared with the controls. Plasma creatinine levels, urea levels and nitrite levels were significantly increased (4, 4.5 and 160% times respectively) as compared with the controls. Histologically, damage to the renal cortex and medulla was observed moderate to severe tubular necrosis and glomerular congestion. Pretreatment with 2.5 mg/kg b.wt. ebselen prevented gentamicin induced damage to medulla; however, renal cortex showed mild damage and biochemically indicators of oxidative stress and nitrosative stress were significantly reduced. Pretreatment with 5 mg/kg b.wt. ebselen prevented gentamicin-induced oxidative damage and nitrosative damage and renal damage almost completely in 78% of the rats, in the other 22% of the rats, ebselen pretreatment reduced gentamicin-induced renal damage. The results of the present study suggest that ebselen may be useful as a nephroprotective agent. 相似文献
20.
A. A. Abdel-Gayoum B. H. Ali K. M. Abdel-Razig A. A. Bashir K. Ghywarsha 《Archives of toxicology》1994,68(10):643-647
Rats were injected with gentamicin at doses of 20, 40 and 80 mg/kg per day for 6 consecutive days. The treatment caused nephrotoxicity as evidenced by dose-related increases in serum creatinine concentration and renal tubular necrosis. The nephrotoxicity was accompanied by reduced renal cortical and fasting blood glucose levels, and by increases in serum lactate concentrations. The activities of cortical malate dehydrogenase and alanine transaminase were significantly reduced by the three doses of gentamicin. On the other hand, aspartate transaminase activity was lowered only by the highest dose of antibiotic used. However, the activity of cortical glucose-6-phosphate dehydrogenase was altered by the 20 and 40 mg/kg doses of gentamicin, but not by the 80 mg/kg dose. The two lower doses reduced the lactate content of the cortex but activated lactate dehydrogenase. The activity of isocitrate dehydrogenase was not altered by any of the gentamicin doses used. 相似文献