Liver-Intestine Axis: Effects of Physical Exercise and Melatonin on Intestinal Implications in Secondary Biliary Cirrhosis

Abstract

Introduction  Modulation of the liver-gut axis, including interventions that reduce oxidative stress, is essential in the management of cirrhosis and in the prevention of its complications. Physical exercise and the use of antioxidants such as melatonin (MLT) improve oxidative stress by increasing the production of endogenous antioxidants, resulting in a better ability of the body to neutralize free radicals.

Objective  To investigate the effects of EX and the use of MLT, the possible biological markers and mechanisms involved in the disease process.

Materials and Methods  Twenty-six male Wistar rats were used, divided into 4 groups: Control (CO), Bile duct ligation (BDL), BDL + EX, and BDL + MLT. Physical exercise (swimming) was conducted daily, starting on the 15th day after BDL surgery, as well as MLT, intraperitoneally at a dose of 20 mg/kg, lasting until the 28th day, the end of the experiment. Blood, liver, and intestine were collected. Statistical analysis was performed using One-Way ANOVA followed by the student-Newman-Keuls test (p < 0.05).

Results  The treatments were effective in preserving the tissue architecture of the liver and intestine. Hepatic integrity enzymes showed a significant reduction in the EX and MLT groups. The treatments reduced lipid peroxidation (LPO) levels, restored antioxidant activity and total antioxidant capacity, as well as lowered the levels of nitric oxide metabolites. It was found that the treatments activated the Nrf2 pathway and reduced inflammatory mediators.

Conclusion  The treatments (EX and MLT) were effective against the damage assessed in this experimental model, suggesting that these interventions may be promising for future clinical use.

Keywords
Cirrhosis; intestine; oxidative stress; physical exercise; melatonin