Genistein attenuates genioglossus muscle fatigue under chronic intermittent hypoxia by down‐regulation of oxidative stress level and up‐regulation of antioxidant enzyme activity through ERK1/2 signaling pathway

Abstract

This study aims to investigate the effects of genistein on contractile properties of genioglossus under chronic intermittent hypoxia (CIH) conditions and its relationship with oxidative stress, antioxidant enzyme, and ERK1/2 signaling pathway. Fifty female Sprague-Dawley rats were randomly divided into five groups 1 week after ovariectomy: the normal control group, the CIH group, the CIH with low-dose, medium-dose, and high-dose genistein groups. Rats in the latter four groups were exposed to CIH for 5 weeks. Twitch tension, tetanic tension, and fatigue resistance of genioglossus were investigated. Malondialdehyde (MDA) and mitochondrial reactive oxygen species (ROS), enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and ERK1/2 were detected. Muscle fatigue resistance and enzymatic activity of GPx, CAT, and SOD were reduced after CIH exposure and improved by different doses of genistein at different degrees. CIH increased the level of ROS and MDA, and they were returned to normal by genistein. The expression of phospho-ERK1/2 is opposite to the changes in muscle fatigue resistance. Chronic intermittent hypoxia decreases fatigue resistance of genioglossus, and genistein treatment reverses the fatigability of genioglossus by down-regulation of oxidative stress level and up-regulation of antioxidant enzymatic activity probably through ERK1/2 signaling pathway.