Melatonin Prevents Cyclosporine-Induced Hepatotoxicity in Rats

Objectives: Cyclosporine A (CsA) is a widely used immunosuppressive agent that is implicated in the formation of free oxygen radicals. Melatonin is known to be a free radical scavenger and an antioxidant agent. This study was designed to investigate the effects of melatonin on CsA-induced liver damage by histopathological examination. Materials and Methods: Thirty-two male rats of Sprague-Dawley origin were divided into 4 groups of 8 and treated for 28 days as follows: group 1 received daily doses of 0.1 ml/kg olive oil s.c.; group 2 received 4 mg/kg of melatonin; group 3 received 10 mg/kg CsA diluted in 0.1 ml/kg olive oil; group 4 was treated with 4 mg/kg melatonin i.p. and 10 mg/kg CsA s.c. Finally, the rats were sacrificed by terminal anesthesia, and liver tissue specimens were processed for light microscopy, stained with HE and examined under a light microscope. Results: Specimens of the control group showed normal liver histology, whereas group 3 showed major histopathological changes, such as cytoplasmic vacuolization, dilatation of the sinusoids, apoptosis and many mitotic figures. In group 4, the normal histology of the liver was preserved, although apoptosis, mitotic figures and cytoplasmic vacuolization were still infrequently observed. Nevertheless, there were significant differences between group 2 (melatonin) and group 3 (CsA) and between group 3 (CsA) and group 4 (CsA + melatonin) concerning these 3 parameters (vacuolization, sinusoidal dilatation and apoptosis). Conclusion: The results of this study suggest that CsA-related liver toxicity in rats could be significantly reduced by melatonin administration.