Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury.
It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.
Bhalodia
Yagnik
Y
Department of Pharmacology, Smt. R. B. Patel Mahila Pharmacy College, S.N.D.T. Women's University, Atkot, Rajkot, Gujarat, India.
Sheth
Navin
N
Vaghasiya
Jitendra
J
Jivani
Nurudin
N
D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D015415:Biomarkers; D000960:Hypolipidemic Agents; D006710:Homocysteine; D011345:Fenofibrate; D000077333:Telmisartan