The Effects of Melatonin on Elevated Liver Enzymes During Statins Treatment

Introduction Statins are widely used in the treatment and prevention of lipid metabolism disorders. They are generally well tolerated but not devoid of side effects. These include, among others, muscular symptoms, arthritis, headaches, gynecomastia. Myositis and rhabdomyolysis associated with increased activity of creatinine kinase and serum creatinine levels are rare but serious adverse events of statin therapy. The risk of these complications is increased in elderly patients with chronic diseases and in alcohol abusers.

Furthermore, statins cause hepatotoxic effect which is observed in several percent of treated patients, usually in the first weeks of the therapy . Most frequently it is manifested by asymptomatic increase in the level of aspartate and alanine aminotransferase. This is usually a temporary increase, but in some patients the level of these enzymes exceeds 3 times the normal limit, which is a matter of concern. In such cases, patients expect the decision to discontinue the treatment or to administer hepatoprotective drugs. Acetylcholine, sylibinin, phospholipids and other drugs used for this purpose are not always effective. Therefore, there is still search for alternative drugs for the protection of liver.

In own study melatonin was used for this purpose because previous experimental studies had demonstrated that it protected liver against harmful effects of many toxic agents as well as the consequences of ischemia-reperfusion model.

The liver is an organ in which there comes to intensive metabolic and detoxification processes. In their course large amounts of reactive oxygen species are generated and they exert a toxic effect on hepatocytes. A complex antioxidant system - in which metabolized there melatonin (pineal and from other sources) is an important part - prevents that.

The main melatonin metabolic pathway in the liver is through hydroxylation pathway at the C-6 position by 6-hydroxylase and P450 cytochromes (CYP1A1, CYP1A2, CYP2P19, CYP1B1 isozymes). The 6-hydroxymelatonin, formed in this process, is conjugated with sulphate and glucuronide to 6-hydroxymelatonin sulphate or glucuronide. In this process melatonin and its metabolites exert high antioxidant activity.