Influence of Oxidative Stress on Muscle and Bone

University dissertation from Uppsala : Acta Universitatis Upsaliensis

Abstract: Reactive oxygen species (ROS) induce oxidative stress and although are primarily recognized for playing a deleterious biological role, they can be beneficial to cell systems. ROS are extremely short-lived and normally tightly regulated by antioxidant defence systems. Cells react to oxidative stress in different ways, which primarily depends on cell type, stress severity, or both. There is a general limitation in extrapolating to humans conclusions drawn from in vitro and animal studies because of important species-specific differences. Therefore, the general aim of this thesis was to study the influence of oxidative stress on human muscle and bone in vivo.In paper I we presented a one-step HPLC method optimized for the simultaneous determination of purine degradation products in small microdialysis samples. The clinical utility of the method was successfully tested in a patient with traumatic brain injury. In paper II we evaluated microdialysis as an in vivo method to characterize the relative kinetics of ROS-related metabolites in human skeletal muscle exposed to ischaemia-reperfusion. Results indicated that microdialysis was feasible and safe to use in monitoring metabolic events during tourniquet-assisted surgery. In paper III we investigated the association between an oxidative stress marker (urinary 8-iso-PGF2?) and bone mineral density (BMD) and whether ?-tocopherol modified the association. The main finding was the negative association between 8-iso-PGF2? and BMD and that the association was further dependent on serum ?-tocopherol level. In paper IV we performed a randomized controlled trial to evaluate the influence of Q10 supplementation on exercise performance and metabolites of muscular damage. We did not observe any effects on exercise capacity after 8 weeks of Q10 administration. Nor did we find a significant effect on serum markers related to oxidative stress.In conclusion we have studied the influence of oxidative stress on muscle and bone in vivo in humans. The oxidative stress was triggered by four different causes (trauma, ischemia-reperfusion, ageing, and exercise exhaustion).