الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The present study was conducted to investigate the effect of both PPARα and γ agonists in MTX-induced nephrotoxicity in rats. In the present study, male albino rats were randomly divided into 8 groups; control (untreated), animals treated with fenofibrate (150 mg/kg), pioglitazone (5 mg/kg), fenofibrate+pioglitazone, MTX (20 mg/kg, i.p), MTX+ fenofibrate, MTX+ pioglitazone and MTX+ fenofibrate+pioglitazone. Administration of fenofibrate and pioglitazone was started 10 days before MTX administration and continued for further 5 days after MTX administration. br Results showed that kidney/body weight ratios in fenofibrate and pioglitazone groups did not significantly differ -#102;-#114;-#111;-#109; that of control. On the other hand, kidney/body weight ratios in MTX group significantly increased compared to control group. Administration of fenofibrate and pioglitazone did not statistically decrease the kidney/body weight ratio. br Administration of single dose of MTX (20 mg/kg, i.p) caused significant deterioration in renal function, designated by the increase in serum levels of both urea and creatinine as compared with control group. Pretreatment with either fenofibrate (150 mg/kg) or pioglitazone (5 mg/kg) before MTX caused a significant decrease in serum levels of both urea and creatinine as compared with their respective MTX-treated group. br In renal samples -#102;-#114;-#111;-#109; MTX-treated group, MTX caused oxidative stress, as evident by the significant decrease in renal GSH and catalase. Pretreatment with either fenofibrate (150 mg/kg) or pioglitazone (5 mg/kg) before MTX significantly reversed the oxidative effect of MTX on renal GSH and catalase. Interestingly, administration of both fenofibrate (150 mg/kg/day) and pioglitazone (5 mg/kg/day) alone, without MTX, resulted in a significant decrease in renal GSH levels compared to control group. br MTX also significantly increased renal MDA and NO compared to control group, which was reversed by pretreatment with either fenofibrate (150 mg/kg) or pioglitazone (5 mg/kg) before MTX administration. Interestingly, administration of both fenofibrate (150 mg/kg/day) and pioglitazone (5 mg/kg/day) alone, without MTX resulted in a significant increase in renal NO levels compared to control group. br The present study also revealed the anti-inflammatory effect of pioglitazone by its ability to reduce MTX-induced increase in renal TNF-α level. Pretreatment with fenofibrate before MTX did not reduce the renal TNF-α level.