Study of seal oil in reducing the nephrotoxicity of cyclosporine A

Yang, Wei, 1975- (2003) Study of seal oil in reducing the nephrotoxicity of cyclosporine A. Masters thesis, Memorial University of Newfoundland.

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Abstract

Nephrotoxicity is a common and serious side effect associated with cyclosporine A (CsA). Fish oil, rich in ω-3 polyunsaturated fatty acids (PUFAs), has been reported to be beneficial in alleviating the toxicities induced by CsA. Seal oil is another source of ω-3 PUFAs. This project was designed to investigate the potential of using seal oil to reduce the nephrotoxicity of CsA. -- The cytotoxicity of CsA alone and in combination with seal oil emulsion, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), main PUF As in seal oil, was determined using the MTT assay and lactate dehydrogenase (LDH) leakage in LLC-PK1 cell line. The effects of seal oil on the in vivo nephrotoxicity of CsA were investigated on two different experimental protocols: In the first experiment, CsA in 20% of seal oil or com oil emulsion was administered to SD rats at 50 mg/kg/day p.o. or 25 mg/kg/day i.p. for 28 days. In the second experiment, rats were kept on diets containing 7% sunflower oil, or mixture of 5.95% seal oil with 1.05% sunflower oil, four weeks prior to and during the four-week i.v. administration of normal saline (control) or CsA (15 mg/kg/day). -- The results of the in vitro studies revealed that DHA reduced the cytotoxicity induced by CsA. In vivo studies demonstrated that the nephrotoxicity associated with CsA was attenuated by the concomitantly supplemented seal oil. The possible mechanism of beneficial effects of seal oil may be exerted via modulating biosynthesis of prostanoids, leading to a higher ratio of prostaglandins to thromboxanes production, with a net favorable vasodilatory effect.

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