Oxytocin for Oxidative Stress and Inflammation

Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure gases at depth, prolonged cold water immersion and inadequate recovery from sustained physical exertion negatively impact individual and team performance. Biotechnologies that could mitigate the effects of cold as well as support physical recovery represent a significant unmet need for the NSW operational community. Oxytocin (OT) has a wide range of actions both locally in the brain and peripherally in the body including skeletal muscle. These peripheral effects can be mediated by classic ligand-receptor activation given the abundant expression of the oxytocin receptor in peripheral tissues, along with local expression of OT in peripheral tissues where it is likely to act in an autocrine manner. Exogenous OT via intranasal administration is FDA Investigational New Drug (IND)-approved and has been demonstrated as an easy and safe method to increase circulating OT concentrations that may augment actions on peripheral tissues. Due to the pleiotropic effects of OT on whole body metabolism, thermogenesis, stress responses, pain, mood, inflammation, appetite, glycemic control, skeletal homeostasis, and skeletal muscle repair and regeneration, there is increasing interest in the administration of exogenous OT for benefits to human health, performance and resilience. However, the biological mechanisms by which OT exerts tissue-specific effects (e.g., skeletal muscle) remain poorly understood, particularly in humans. This project is designed to significantly advance this understanding while testing the central hypothesis that intranasally administered OT attenuates systemic and skeletal muscle oxidative stress and inflammation induced by the combined stressor of resistance swim exercise and hyperoxia.