Chapter 28 - Dietary Fish Oil Protects Against Gentamicin, Cisplatin, Uranyl Nitrate, and Nitric Oxide Donor/Metabolite-Induced Nephrotoxicity and Oxidative Damage in Rat Kidney

Abstract

Long-term exposure to certain pharmaceutical and environmental agents such as gentamicin, cisplatin, uranyl nitrate, sodium nitroprusside, sodium nitrite, and arginine, produce nephrotoxicity and cause severe damage to the kidneys. Dietary consumption of fish and/or fish oil (FO) containing long-chain n–3 (LCn3) polyunsaturated fatty acids is known to have extensive health benefits. They have been shown to retard the progression of various forms of cancers, depression, diabetes, arthritis, asthma, cardiovascular, neurological, and renal disorders and have also been found to improve kidney functions. Here, we discuss the protective effects of FO on drug- and chemical-induced nephrotoxicity and oxidative damage. The administration of the above mentioned agents caused severe renal damage as evident by an increase in serum creatinine, cholesterol, and blood urea nitrogen along with a decrease in certain enzymes of carbohydrate metabolism, brush border membrane (BBM), and oxidative stress. BBM phosphate (Pi) transport in the rat kidney was also reduced. However, dietary FO consumption markedly reversed the effects of these drugs and chemicals by increasing energy metabolism, BBM integrity, and Pi transport. These drugs are known to generate reactive oxygen species that cause damage to mitochondria, microsomes, peroxisomes, lysosomes, and BBM of renal proximal tubules, thus altering their functions. Dietary LCn3 fatty acids in FO affect membrane organization, fluidity, permeability, and other properties by altering membrane fatty acid composition. FO-induced changes, at least in part, can also be attributed to improved antioxidant defense mechanisms that accelerate repair and regeneration of damaged cellular membranes. In conclusion, we propose that dietary FO consumption may provide a cushion for prolonged clinical use of these drugs by ameliorating drug-induced nephrotoxicity and prevents multiple adverse effects inflicted upon by the exposure of these environmental contaminants.