Coumarin attenuates tamoxifen-caused liver damage by reducing oxidative stress index

Introduction: Tamoxifen (TMX) is an anti-estrogen medication used in the treatment and prevention of all stages of estrogen-dependent breast cancer. However, one of the most important side effects of TMX was hepatotoxicity. In this study, we investigated the therapeutic effects of coumarin (CM) as a natural antioxidant, on TMX-induced acute liver injury in rats. Methods: Five groups of rats were used: Control; TMX (۵۰ mg/kg, PO); TMX+ Low CM (۱۰ mg/kg); TMX+ Med CM (۵۰ mg/kg) and TMX+ High CM (۱۰۰ mg/kg). TMX and CM were given intragastrically for ۱۰ consecutive days. Sera was test for albumin as negative acute phase protein, liver enzymes and total oxidant status to total antioxidant capacity ratio (OSI) using commercial kits. Results: Our data showed that oral administration of TMX causes liver injury and oxidative stress. Treatment with coumarin could reduce TMX hepatotoxicity side effects evidenced through dose-dependent reduction of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities with considerable elevation in serum albumin and total protein. Moreover, treatment with coumarin ameliorated TMX-induced oxidative stress, evidenced by a considerable decrease in oxidative stress index (OSI). Somehow, this index has decreased significantly (p<۰.۰۵) from ۲.۶۷۵±۰.۲۱ in TMX group to ۱.۵۰۱±۰.۲۴ in Low concentration of coumarin. Conclusion: Our outcomes recommend that coumarin protects the integrity of the hepatic tissue by stabilizing the reactive oxygen species, decreasing Liver enzymes. According to the results of the study, coumarin in patients receiving Tamoxifen could be useful to reduce side effects and oxidative stress.

کلیدواژه ها:

Tamoxifen ، Oxidative stress Index ، Coumarin ، Liver injury ، Albumin