Abstract of research

PROTECTIVE EFFECT OF DIETARY FISH OIL ON CYCLOSPORINE AINDUCED NEPHROTOXICITY IN RATS

Samy Ali Hussein, Omayma A. Ragab and Mohammed A. El-Eshmawy

Abstract

Cyclosporine A (CsA) is a lipophilic cyclic polypeptide composed of 11 amino acids, seven of which are N-methylated. It has been utilized clinically as a potent immunosuppressant to prevent allograft rejection in various organ transplantations and to treat systemic and local autoimmune disorders, but it can impair renal function. CsA-induced nephrotoxicity results from increased production of free radical species in the kidney. The present study was designed to investigate the possible protective effect of dietary fish oil (FO) on CsA-induced nephrotoxicity in rats. Eighty male rats were divided into four equal groups. Group 1 rats received no drugs and served as control, group 2 normal rats were treated with (dietary fish oil) omega-3 fatty acids 270 mg/kg b.w oral dose daily, group 3 rats treated with CsA (25 mg/kg body weight, orally for 21 days) to induce nephrotoxicity, groups 4 rats received dietary fish oil for 21 days before, 21 days concurrently during CsA administration and 21 days later after nephrotoxicity induction. Blood samples for serum separation and kidney tissue specimens were collected three times at weekly interval from the last dose of CsA administration. Serum glucose, total cholesterol, triacylglycerols, phospholipids, creatinine, uric acid, urea, sodium, potassium, inorganic phosphorus, total protein, albumin, haptoglobin levels, lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) activities were also determined. Moreover, kidney tissue malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), total antioxidant capacity (TAO) levels, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were also determined. The results revealed that CsA-induced nephrotoxicity caused asignificant increase in serum glucose, renal functions tests, lipid profiles and serum marker enzymes (LDH and GGT) with a significant decrease in serum total protein, albumin and electrolytes concentrations, which were reversed upon treatment with dietary fish oil. In addition, CsA administration induced a significant elevation in lipid peroxidation (MDA) along with a significant decrease in antioxidant enzyme activities, non enzymatic antioxidant, total antioxidant capacity and nitric oxide level in the rat kidney. Meanwhile, dietary fish oil administration improved renal functions, by a significant decrease in peroxidative levels and increase in antioxidant status. These results indicate the renoprotective potential and usefulness of dietary fish oil, as an excellent source of antioxidants, in modulating CsA-induced nephrotoxicity.