Protective effect of docosahexaenoic acid against cyclosporine A-induced nephrotoxicity in rats: a possible mechanism of action.

The aim of this experimental study was to investigate whether, and how then, docosahexaenoic acid (DHA) could alleviate the cyclosporine A (CsA)-induced nephrotoxicity. Three main groups of Sprague-Dawley rats were treated orally with CsA (25 mg/kg), DHA (100 mg/kg), and CsA along with DHA. A corresponding control group was also used. DHA administration significantly reduced CsA-induced nephrotoxicity and associated hyperlipidemia and proteinuria as assessed by estimating serum triacylglycerol, serum total cholesterol, serum total protein, serum urea, and creatinine clearance. Furthermore, urinary excretions of protein and N-acetyl-β-D-glucosaminidase were significantly inhibited following DHA administration. DHA supplementation slightly attenuated the oxidative damage in kidney tissues as evaluated by the levels of thiobarbituric acid-reacting substances and protein carbonyl content in the kidney homogenate, although there were no significant differences between CsA-intoxicated and DHA-treated animals. Moreover, DHA treatment significantly restored total nitric oxide (NO) levels in both renal tissues and urine. This study demonstrates the ability of DHA to ameliorate CsA-induced renal dysfunction, which might be beneficial to enhance the therapeutic index of CsA. The data suggest that the protective potential of DHA in the prevention of CsA nephrotoxicity in rats was mainly associated with the increase of total NO bioavailability in renal tissues. Nevertheless, the exact independent mechanism in which DHA exerts its beneficial effect is yet to be fully elucidated.