Objectives: In this study, it was aimed to investigate the effects of melatonin on oxidative stress parameters, expression levels of dimethylarginine dimethylaminohydrolase (DDAH) which involved in nitric oxide metabolism, and histopathological changes in the liver tissue in experimental hypercholesterolemia.

Material and Methods: Rats were divided into 4 groups: a) Control, b) Hypercholesterolemia (HCT), c) Melatonin administrated concurrently with cholesterol diet (HCT-MEL, prophylactically), d) Melatonin administrated only during the last 2 weeks of cholesterol diet feeding (HCT-2MEL, therapeutically) groups.

Results: Although an increase was observed in the MDA levels, the DDAH protein expression and GSH levels were found to decrease with hypercholesterolemia. MDA levels, GSH activity and DDAH expression were normalized with melatonin administrations. Significant changes such as sinusoidal congestion, cloudy bloating, periportal cell infiltration, periacinary lubrication, and apoptosis were observed in the liver tissue by hypercholesterolemia. In the HCT-MEL group, the severity of the fat in the periportal and midzonal region was lowere compared to the HCT group. Histopathologically when the two treatment groups are compared, prophylactic melatonin was more effective than its therapeutic use.

Conclusion: Melatonin may be a hepatoprotective and/or therapeutic agent with antioxidant effect, and regulator of nitric oxide metabolism in prevention of histopathological changes in liver pathology in diet-induced hypercholesterolemia.