Antioxidant nutrients protect against cyclosporine A nephrotoxicity

• Published in: Toxicology (Amsterdam) 2003-07, Vol.189 (1), p.99-111
• Main Authors: Parra Cid, T., Conejo Garcı&#x0301, a, J.R., Carballo Álvarez, F., de Arriba, G.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Ascorbic Acid - pharmacology; Cyclosporine - adverse effects; Cyclosporine - antagonists & inhibitors; Cyclosporine A; Eicosanoids; Free radicals; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; Humans; Immunosuppressive Agents - adverse effects; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Kidney Diseases - prevention & control; Kidney Transplantation; Lipid peroxidation; Lipid Peroxides - biosynthesis; Lipid Peroxides - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Thiobarbituric acid reactive substances (TBARS); Thromboxane; Thromboxanes - biosynthesis; Thromboxanes - metabolism; Vitamin E; Vitamin E - pharmacology
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(03)00156-2

The immunosuppressive drug cyclosporine A (CsA) has been successfully used in several diseases with immunological basis and in transplant patients. Nephrotoxicity is the main secondary effect of CsA treatment. Although the mechanisms of nephrotoxitity are not completely defined, there is evidence that suggests the role of reactive oxygen species (ROS) in its pathogenesis. It has been demonstrated in numerous in vivo and in vitro experiments that CsA induced renal failure and increased the synthesis of ROS, thromboxane (TX) and lipid peroxidation products in the kidney. Furthermore, CsA modified the expression and activity of several renal enzymes (ciclooxygenase, superoxide-dismutase, catalase and glutathione-peroxidase). Antioxidant nutrients (e.g. Vitamins E and C) can neutralize some of the effects that CsA produced in the kidney. Thus, Vit E inhibited the synthesis of ROS and TX and the lipid peroxidation process induced by CsA in kidney structures. Antioxidants can also improve renal function and histological damage produced by CsA administration. Although there are few data in humans treated with CsA, the possibility exists that antioxidants can also neutralize CsA nephrotoxicity and LDL oxidation. Thus, antioxidant nutrients could have a therapeutic role in transplant patients treated with CsA.