Design of Antioxidant Nanoparticle, which Selectively Locates and Scavenges Reactive Oxygen Species in the Gastrointestinal Tract, Increasing The Running Time of Mice

Abstract

Excess reactive oxygen species (ROS) produced during strong or unfamiliar exercise cause exercise-induced gastrointestinal syndrome (EIGS), leading to poor health and decreased exercise performance. The application of conventional antioxidants can neither ameliorate EIGS nor improve exercise performance because of their rapid elimination and severe side effects on the mitochondria. Hence, a self-assembling nanoparticle-type antioxidant (RNP^O ) that is selectively located in the gastrointestinal (GI) tract for an extended time after oral administration is developed. Interestingly, orally administered RNP^O significantly enhances the running time until exhaustion in mice with increasing dosage, whereas conventional antioxidants (TEMPOL) tends to reduce the running time with increasing dosage. The running (control) and TEMPOL groups show severe damage in the GI tract and increased plasma lipopolysaccharide (LPS) levels after 80 min of running, resulting in fewer red blood cells (RBCs) and severe damage to the skeletal muscles and liver. However, the RNP^O group is protected against GI tract damage and elevation of plasma LPS levels, similar to the nonrunning (sedentary) group, which prevents damage to the whole body, unlike in the control and TEMPOL groups. Based on these results, it is concluded that continuous scavenging of excessive intestinal ROS protects against gut damage and further improves exercise performance.

Keywords: exercise-induced gastrointestinal syndrome; high-intensity running; leaky gut; polymeric nanoparticle antioxidants; reactive oxygen species.