The Beneficial Effect of Melatonin for Cyclosporine Hepatotoxicity in Rats

Abstract

In humans the immunosuppressive drug cyclosporine A (CsA) has been used successfully in organ transplantation and in the treatment of autoimmune disorders.1 CsA, however, causes side effects that occur mainly in the kidney2 and 3 but also in the liver.1 and 2 Although, the mechanisms leading to the hepatic side effects are not fully understood, several reports have strongly suggested that reactive oxygen production is a common mechanism of CsA toxicity.1

Melatonin, a pineal secretory product, has been reported to have antioxidant properties in addition to its known hormonal activities.4, 5, 6 and 7 Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals.4, 5, 6 and 7 Melatonin may have a protective effect on the deteriorated hepatic function that results from oxygen free radicals in the CsA-induced hepatotoxicity.

To test this hypothesis, CsA hepatotoxicity was induced by subcutaneous injection of CsA for 14 days. Protection by melatonin was done by the injection with melatonin intraperitoneally at the time of CsA injection. Total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (γ-GT) levels in serum were measured to estimate hepatic function. Malondialdehyde, which gives an indirect index of oxidative injury,8 was also measured.