Effects of melatonin in a standard model of diethylnitrosamine-induced rat cirrhosis

Cirrhosis represents the final stage of chronic liver disease and is characterized by fibrosis with disruption of liver architecture and function. Diethylnitrosamine (DEN) is a hepatotoxin known to induce oxidative stress, while melatonin (MLT) is a potent antioxidant. This study aimed to investigate the effects of MLT in an experimental animal model of DEN-induced cirrhosis. Male Wistar rats (mean weight 180 g) were divided into 4 groups: control (CO), CO + MLT, DEN, and DEN + MLT. The experimental protocol involved intraperitoneal administration of DEN (50 mg/kg) twice a week for 7 weeks. MLT was administered daily from the fifth to the seventh week. The activity of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase was significantly elevated in the DEN group but was significantly decreased in the DEN + MLT group. Rats in the DEN + MLT group also exhibited greater weight gain. Inducible nitric oxide synthase and transcription factor NF-κB (p65) expression was increased in the DEN group but significantly decreased in the DEN + MLT group. Likewise, alpha smooth muscle actin was increased in the DEN group but significantly decreased in the DEN + MLT group. Overall, MLT significantly reduced all study parameters and showed a protective modulatory effect on inflammation, fibrosis, and cirrhosis.