Investigating the mechanistic role of oxidative stress in brain–gut axis disruption in rat model

Abstract

This study investigated the impact of endotoxin exposure on intestinal oxidative stress and white blood cell (WBC) subtypes in a rat model to understand its role in disrupting brain–gut communication. Lipopolysaccharide (LPS)-derived endotoxin was intraperitoneally injected into Sprague Dawley rats at varying doses of 250, 500, 750, and 1,000 μg per kg body weight four times weekly. The intestinal oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA)) and WBC differentials (WBCs, lymphocytes, monocytes, neutrophils) were measured. The endotoxin exposure significantly increased intestinal oxidative stress by decreasing the levels of SOD, CAT, and GSH, and it increased the level of MDA compared with the control group (p < 0.05). The endotoxin exposure caused nonspecific inflammatory response marked with increased counts of WBCs and neutrophils (p < 0.05). The monocyte percentage decreased (p < 0.05), while the lymphocyte percentage remained unchanged (p > 0.05). These findings suggest that endotoxin disrupts the gut’s antioxidant system and triggers inflammation, which could potentially lead to gut dysfunction. The findings also suggest a link between gut dysfunction and brain function, which implies a possible indirect effect of endotoxin on body reserve and reproduction via the brain–gut axis compromise. The study concluded that an understanding of oxidative stress and immune compromise, as reflected by changes in intestinal oxidative stress biomarkers and WBC subtypes, offers potential targets for therapeutic development against various diseases and performance issues related to the brain–gut axis.