Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

World J Gastroenterol. 2022 Jan 21;28(3):348-364. doi: 10.3748/wjg.v28.i3.348.

Abstract

Background: Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential.

Aim: To evaluate MLT's effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis.

Methods: Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis.

Results: BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower (P < 0.001) n the groups that received MLT. DNA damage was also lower (P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1β, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT (P < 0.001).

Conclusion: When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

Keywords: Antioxidants; Bile duct ligation; Melatonin; Oxidative stress; Secondary biliary cirrhosis.

MeSH terms

  • Animals
  • DNA Damage
  • Liver Cirrhosis, Biliary*
  • Male
  • Melatonin* / pharmacology
  • Oxidative Stress
  • Rats
  • Rats, Wistar

Substances

  • Melatonin