Ischemia/reperfusion (I/R) is one of the common reasons for acute kidney injury (AKI) and we need to develop effective therapies for treating AKI. We investigated the role of fenofibrate against I/R-induced AKI and associated hepatic dysfunction in rats. In male wistar albino rats, renal pedicle occlusion for 40 min and 24 h reperfusion resulted in AKI. I/R-induced AKI was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium and urinary microproteins. Oxidative stress in rat kidneys was quantified by assaying superoxide anion generation, thiobarbituric acid reactive substances, and reduced glutathione levels. AKI-induced hepatic damage was quantified by assaying serum aminotransferases, alkaline phosphatase and bilirubin levels. Moreover, serum cholesterol, high density lipoprotein and triglycerides were quantified. Hematoxylin-eosin staining of renal and hepatic tissues was done and the kidney and liver injury scores were determined. Immunohistology of endothelial nitric oxide synthase (eNOS) was done in rat kidneys. Fenofibrate was administered for 1 week before subjecting rats to AKI. In separate group, the nitric oxide synthase inhibitor, L-nitroarginine methyl ester (L-NAME) was administered prior to fenofibrate treatment. In I/R group, significant alteration in the serum/urine parameters indicated AKI and hepatic dysfunction along with marked increase in kidney and liver injury scores. Treatment with fenofibrate attenuated AKI and associated hepatic dysfunction. Moreover, I/R-induced decrease in renal eNOS expression was abrogated by fenofibrate. Pre-treatment with L-NAME abolished fenofibrate mediated reno- and hepato-protective effects. In conclusion, fenofibrate attenuates I/R-induced AKI and associated hepatic dysfunction putatively through modulation of eNOS expression.
Keywords: acute kidney injury; endothelial nitric oxide synthase; fenofibrate; ischemia; liver; oxidative stress.
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