Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status

Physical exercise induces inflammatory and oxidative markers production in the skeletal muscle and this process is under the control of both endogenous and exogenous modulators. Recently, molecular hydrogen (H-2) has been described as a therapeutic gas able to reduced oxidative stress in a number of conditions. However, nothing is known about its putative role in the inflammatory and oxidative status during a session of acute physical exercise in sedentary rats. Therefore, we tested the hypothesis that H-2 attenuates both inflammation and oxidative stress induced by acute physical exercise. Rats ran at 80% of their maximum running velocity on a closed treadmill inhaling either the H-2 gas (2% H-2, 21% O-2, balanced with N-2) or the control gas (0% H-2, 21% O-2, balanced with N-2) and were euthanized immediately or 3 h after exercise. We assessed plasma levels of inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. In addition, we evaluated the phosphorylation status of intracellular signaling proteins [glycogen synthase kinase type 3 (GSK3 alpha/beta) and the cAMP responsive element binding protein (CREB)] that modulate several processes in the skeletal muscle during exercise, including changes in exercise-induced reactive oxygen species (ROS) production. As expected, physical exercise increased virtually all the analyzed parameters. In the running rats, H-2 blunted exercise-induced plasma inflammatory cytokines (TNF-alpha and IL-6) surges. Regarding the oxidative stress markers, H-2 caused further increases in exercise-induced SOD activity and attenuated the exercise-induced increases in TBARS 3 h after exercise. Moreover, GSK3 alpha/beta phosphorylation was not affected by exercise or H-2 inhalation. Otherwise, exercise caused an increased CREB phosphorylation which was attenuated by H-2. These data are consistent with the notion that H-2 plays a key role in decreasing exercise-induced inflammation, oxidative stress, and cellular stress.