Amelioration of chronic cyclosporine A-induced nephrotoxicity by telmisartan in rats

作者：Al Amran Fadhil G^*; Hadi Najah R; Kamoona Talib H; Kadhum Zahraa J

来源：African Journal of Pharmacy and Pharmacology, 2011, 5(4): 500-505.

• Cyclosporine A
• nephrotoxicity
• oxidative stress
• telmisartan

Nephrotoxicity is a major problem of Cyclosporine A (CsA) treatment, despite its beneficial role in organ transplantation and in a variety of immunologic disorders. This study was undertaken to investigate the potential renoprotective role of telmisartan in amelioration of chronic CsA induced nephrotoxicity. The rats were randomized into 4 equal groups. Group 1 received normal saline (control), group 2 received Cremophor EL and ethanol (CsA vehicle), group 3 received CsA 25 mg/kg/day s.c and group 4 received telmisartan 3 mg/kg/day orally in addition to CsA. The rats were pair fed with a standard chow diet throughout the experiment period (8 weeks). CsA nephrotoxicity was assessed in terms of increased S.Cr (from 0.52 +/- 0.16 to 1.29 +/- 0.20 mg/ml), blood urea (from 24.69 +/- 1.89 to 75.88 +/- 2.33 mg/ml) and serum K (from 3.43 +/- 0.18 to 5.23 +/- 0.43 meq/l). CsA also caused significant increase (p<0.01) in MDA (from 0.74 +/- 0.13 to 2.96 +/- 0.43 nmol/mg protein) and significant decrease (p<0.01) in GSH and catalase in renal tissue. Telmisartan failed to restore the altered renal functions. On the other hand, it causes a significant improvement in the histological changes including the tubulointerstitial fibrosis and arteriolopathy (p<0.01). It also caused significant reduction (p<0.01) in CsA-induced oxidative stress. These findings suggested that telmisartan has a promising renoprotective effect against chronic CsA induced nephrotoxicity.

• 出版日期2011-4