Inhaled molecular hydrogen attenuates intense acute exercise-induced hippocampal inflammation in sedentary rats.

Physical exercise-induced inflammation may be beneficial when exercise is regular but it may be harmful when exercise is intense and performed by unaccustomed individuals/rats. Molecular hydrogen (H) has recently emerged as a powerful anti-inflammatory, antioxidant and anti-apoptotic molecule in a number of pathological conditions, but little is known about its putative role under physiological conditions such as physical exercise. Therefore, we tested the hypothesis that H decreases intense acute exercise-induced inflammation in the hippocampus, since it is a brain region particularly susceptible to inflammation. Moreover, we also assessed hippocampus oxidative status. Rats ran on a sealed treadmill inhaling either the H (2% H, 21% O, balanced with N) or the control gas (0% H, 21% O, balanced with N) and hippocampal samples were collected immediately or 3 h after exercise. We measured hippocampal levels of cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. Exercise increased TNF-α, IL-6 and IL-10 immediately after the session, whereas no change in IL-1β levels was observed. Conversely, exercise did not cause any change in SOD activity, TBARS and NOx levels. H inhibited the exercise-induced surges in TNF-α and IL-6, and potentiated the IL-10 surge, immediately after the exercise. Moreover, no change in IL1-β levels of rats inhaling H was observed. Regarding the oxidative stress markers, H failed to cause any change in SOD activity, TBARS and NOx levels. No significant change was observed in any of the assessed parameters 3 h after the exercise bout. These data are consistent with the notion that H acts as a powerful anti-inflammatory agent not only down-modulating pro-inflammatory cytokines (TNF-α and IL-6) but also upregulating an anti-inflammatory cytokine (IL-10) production without affecting the local oxidative stress status. These data indicate that H effectively decreases exercise-induced inflammation in the hippocampus, despite the fact that this region is particularly prone to inflammatory insults.