Effects of melatonin or physical exercise application in rats with hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) is characterized by liver abnormalities, hypoxemia, and intrapulmonary vasodilatation. Currently, liver transplant is the only effective treatment, as there are no established pharmacological therapies for HPS. Bile duct ligation (BDL) is an experimental model widely used to study the pathophysiology of HPS, as it replicates disease abnormalities. This study aimed to evaluate the effects of melatonin (MLT) or physical exercise (EX) on BDL-induced HPS. Twenty-six male Wistar rats were divided into 4 groups: control (CO), BDL, BDL + MLT, and BDL + EX. Starting on day 15, MLT (20 mg/kg) was administered intraperitoneally once daily, and the EX protocol was implemented, consisting of swimming sessions in a 50-cm-deep tank every other day. All animals were euthanized on day 29, when blood, liver, and lung samples were collected for analysis. The BDL group showed significant liver damage, as evidenced by elevated liver enzyme levels, the presence of fibrous septa and nodules in the liver, an increased diameter of intrapulmonary vessels, impaired gas exchange in arterial blood gas analysis, increased oxidative stress, and DNA damage. The BDL + MLT and BDL + EX groups showed liver parenchyma restructuring, reduced intrapulmonary vasodilatation, improved gas exchange, and reduced oxidative stress and DNA damage compared with the BDL group. Our results suggest that both MLT and EX exert beneficial effects on BDL-induced HPS, reducing liver and lung abnormalities, improving antioxidant defenses, and decreasing DNA damage through modulation of the antioxidant system.