Monoamine oxidase (MAO) activity and MAO-derived hydroxyl radical production in mouse model of hepatic ischemia-reperfusion injury

Objective: There are various studies that have been published indicating that reactive oxygen species are produced in large quantities in post-ischemic reperfusion and this oxidative burst mediates the severity of the damage. It has been previously suggested that monoamine oxidase (MAO) is a potential source of hydrogen peroxide (H₂O₂) in early reperfusion; and mitochondrial hydroxyl radicals generated from H₂O₂ during MAO metabolism serve as a contributor to tissue injury. The aim of this study was to investigate the possible contribution of elevated activities of MAO isoforms to the generation of reactive oxygen species and lipid peroxidation in hepatic ischemia-reperfusion injury in mice. Methods: After 45 minutes of partial ischemia followed by 5 hours of reperfusion performed on mouse liver. Serum lactate dehydrogenase and transaminase activities were measured as indices of hepatic injury. Lipid peroxidation, glutathione content and redox state, antioxidant enzyme activities, total MAO, MAO-A and -B activities and MAO-dependent H₂O₂ release in liver tissue were determined. Results: MAO-A and -B activities, lipid peroxidation, oxidized glutathione content and H₂O₂ release were found to be increased, while reduced glutathione content, reduced/oxidized glutathione ratio as indice of redox state and antioxidant enzyme activities were decreased in liver tissues of ischemia-reperfusion group when compared to those of control group. A strong positive correlation was found between MAO isoform activities and H₂O₂ release in ischemia-reperfusion group, suggesting that MAO is a potential source of H₂O₂ generation during ischemia-reperfusion. Conclusion: Our study suggests that both MAO isoforms may contribute to reactive oxygen species generation during ischemia-reperfusion, and MAO inhibitors may be used against liver ischemia-reperfusion injury.