Molecular hydrogen downregulates acute exhaustive exercise-induced skeletal muscle damage.

Abstract

Acute exhaustive exercise in sedentary rats causes skeletal muscle damage characterized by elevated oxidative stress, inflammatory cytokine release, and apoptotic signaling. This study examined whether inhalation of molecular hydrogen (H2) could mitigate these responses. Sedentary rats ran to exhaustion on a sealed treadmill while breathing either an H2-containing gas mixture or a control gas. Oxidative stress markers (SOD activity, GSH, TBARS), inflammatory markers (TNF-α, IL-1β, IL-6, IL-10, NF-κB phosphorylation), and apoptotic markers (cleaved caspase-3, Bcl-2, HSP70 expression) were subsequently assessed in skeletal muscle. Exercise alone did not alter SOD activity but elevated TBARS levels; H2 inhalation increased SOD activity and suppressed the TBARS rise. Exercise-induced surges in TNF-α and IL-6, along with NF-κB phosphorylation, were attenuated by H2. Additionally, the exercise-induced increase in cleaved caspase-3 expression was reduced in H2-treated animals. These findings indicate that H2 inhalation effectively suppresses multiple pathways of exercise-induced skeletal muscle damage in unaccustomed organisms.

Mechanism

H2 inhalation enhances SOD activity to reduce lipid peroxidation (TBARS), suppresses NF-κB phosphorylation thereby lowering TNF-α and IL-6 production, and decreases cleaved caspase-3 expression, collectively attenuating exercise-induced skeletal muscle damage.