High Intensity Aerobicexercise Preconditioning Decreases Oxidative Stress Damage Associated With Rat Liver Ischemia-reperfusion Injury

Hepatic ischemia-reperfusion injury (IRI) is a major cause of early organ disfunction following liver surgery. Exercise preconditioning reduces IRI in several settings, but it is unknown if it also protects against hepatic IRI. PURPOSE: Determine the protective effect of different aerobic exercise intensities in liver IRI. METHODS: Twenty-five Wistar rats were divided in 5 groups (n = 5): sedentary (SED), physically active (PA; cage with running wheel) and light (LIR treadmill running at 60% VO2max), moderate (MIR 75% VO2max) and high intensity (HIR 90% VO2max) isocaloric exercise protocols (5d/week, 12 weeks). VO2max was determined at baseline and 12 weeks by indirect calorimetry and aerobic capacity by a treadmill exhaustion test (10o slope, 25 m/min, 5 m/min increments/15 min). At 12 weeks, animals underwent 45 min partial liver ischemia and 24 h reperfusion and were sacrificed. Liver myeloperoxidase activity (colorimetry) and nitration, 4-hydroxynonenal, and carbonyl groups expression (slot blot) was quantified. RESULTS: VO2max was higher in all groups (MIR 67.5 ± 5.3 ml.kg.min-1, p = .009; HIR 66.8 ± 4.8; p = .013; PA 69.5 ± 7.2; p = .004) compared to SED (54.3 ± 3.5), with exception of LIR (62.0 ± 6.4). Aerobic capacity was also significantly higher in all groups (LIR 1247 ± 354 m, p = .024; MIR 1675 ± 384 m, p < .001; HIR 1988 ± 464 m, p < .001; PA 2045 ± 983 m, p < .001) compared to SED controls (410 ± 130 m). Myeloperoxidase activity, an indicator or neutrophil invasion, was lower in all exercised groups compared to SED and inversely correlated with VO2max (r = -.664, p < .001) and aerobic capacity (r = -.757, p < .001) and positively with liver nitration (r = .522, p < .001) and carbonylation (r = .517, p < .01). Nitration was only significantly lower in HIR (162 ± 44 OD, p = .024) compared to SED (243 ± 13 OD). The same was identified for liver protein carbonylation (HIR: 165 ± 34 OD, SED: 372 ± 200 OD; p = .015). VO2max also correlated inversely with carbonylation (r = -.551, p = .018), while aerobic capacity correlated inversely with carbonylation (r = -.430, p = .036) and nitration (r = -.523, p = .009). CONCLUSION: Higher intensity exercise induced greater improvements in VO2max and aerobic capacity. Higher VO2max and aerobic capacity correlated inversely with liver neutrophil invasion and oxidative stress following IRI. ACKNOWLEDGEMENTS: This work was funded by FCT grants UID/DTP/00617/2020, LA/P/0064/2020, PTDC/SAU-DES/4113/2020 and 2022.10037.BD.