Does Physical Inactivity Aggravate Liver Ischemia-Reperfusion Injury? Evidence from a Preclinical Wistar Rat Model

Ischemia-reperfusion injury (IRI) is a major cause of postoperative liver dysfunction after hepatic resection. Physical activity has been shown to protect against cardiac IRI but its effects on hepatic IRI are largely unknown. This study determined, in a preclinical rat model, whether physical activity modulates the hepatic response to ischemia-reperfusion.

Twenty-eight male Wistar rats were assigned to four groups (n = 7) in a 2 × 2 design combining housing (physically inactive vs. voluntary running wheel) and surgery (30 min partial hepatic ischemia followed by 24 h reperfusion vs. sham). Liver injury, inflammation, apoptosis, oxidative stress, endothelial and mitochondrial markers were assessed.

Ischemia increased transaminases, ALP, bile acids and total bilirubin and reduced albumin, confirming IRI. The transaminase rise was similar in physically inactive and active animals (ALT, p = 0.867), indicating that physical activity did not prevent hepatocellular necrosis. However, physically active animals exhibited lower MPO activity, TNF-α, Bax/Bcl-2 ratio and caspase-8, together with higher citrate synthase activity, with significant surgical procedure × activity interactions for MPO (p = 0.035), TNF-α (p = 0.008) and Bax/Bcl-2 (p = 0.026). Oxidative stress, endothelial and mitochondrial markers, mitochondrial respiration and H₂O₂ emission were similar between groups.

Physical activity did not reduce hepatocellular necrosis but attenuated inflammatory and apoptotic responses following hepatic IRI and increased liver mitochondrial content.