Sedentary Lifestyle Worsens Liver Ischemia-Reperfusion Injury Via Inflammation Mediated By Myeloperoxidase In Animal Model

Strategies to prevent or reduce the extent of liver ischemia-reperfusion Injury (IRI) are necessary to improve patient´s health outcomes and tolerability to liver surgery. However, the molecular mechanisms underlying the impact of lifestyle (sedentary behavior or physical activity) on the liver IRI is unclear PURPOSE: Evaluate if sedentary behavior prior to liver surgery worsens the extent of IRI. METHODS: Twenty-eight male Wistar rats were randomly divided into four experimental groups (n = 7): Sedentary Control (SED), Sedentary IRI (SEDIR), Physically Active Control (PA), and Physically Active IRI (PAIR), maintained in12/12 h inverted light/dark cycle, 23 °C, 50-60% humidity, with food and water ad libitum for 4 weeks. Animals in the sedentary group were housed individually in standard cages, and their physical activity was restricted to the limited cage area. Animals in the physically active group were housed in cages equipped with running wheels, allowing them to be physically active. At 4 weeks, animals underwent 30 min partial liver ischemia and 24 h reperfusion and were sacrificed. Blood and liver were collected for biochemical analysis. Liver function, hepatic oxidative stress, as well as inflammatory markers, were measured at the end of the experiment. RESULTS: Liver IRI was manifested by a significant increase in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in IRI groups (p < 0,05). However, no differences were found in the liver ALT activity. Myeloperoxidase (MPO) activity, an indicator of neutrophil invasion, was significantly higher in both IRI groups (SEDIR vs. SED, p < 0,05 and PAIR vs. PA, p < 0,05), and sedentary behavior worsened this tendency (SEDIR vs. PAIR, p < 0,001). No differences were noticed in serum protein C reactive and in liver oxidative markers levels (3-nitrotyrosine, 4-hydroxynonenal, and carbonyl proteins). Even though there is a higher tendency in liver 3-nitrotyrosine and 4-hydroxynonenal levels in the SEDIR group (SEDIR vs. PAIR). CONCLUSIONS: The sedentary behavior seemed to be more prone to increase the extent of liver IRI, suggesting a link between liver inflammation mediated by MPO and sedentary behavior. This work was funded by FCT grants UID/DTP/00617/2020, LA/P/0064/2020 and PTDC/SAU-DES/4113/2020 and 2022.10037.BD.