Inhibition of NOX2 Improves Muscle Tension and Fatigue Resistance in Fast Twitch Skeletal Muscle of Diabetic Rats

Abstract

Chronic hyperglycemic state during diabetes mellitus (DM) has been related to an increase in oxidative stress, which causes damage to skeletal muscle tissue, contributing to the appearance of muscle fatigue, characterized by decreased strength. An increase in the activity of the enzyme NADPH oxidase 2 (NOX2) has been observed in skeletal muscle, and with it an increase in basal ROS production; It has been linked to the alteration of insulin signaling in tissue. Consequently, normal muscle metabolism is affected, compromising the ability of individuals to perform physical activity. Apocynin is a drug that, in addition to being a specific inhibitor of NADPH oxidase, has antioxidant properties reported in experimental models of insulin resistance. However, the effect of NOX2 inhibition on skeletal muscle health during DM is unknown. Therefore, in order to preserve muscle structure and function, the objective of this study was to evaluate the effect of NOX2 inhibition by apocynin on muscle function in an experimental diabetes model. Male Wistar rats (230–250 g) were randomly divided into four groups, among them: control, apocynin control, diabetic and apocynin diabetic, in which diabetes was induced intraperitoneally with streptozotocin (45 mg / kg). Treatment with apocynin (3 mg / kg / day) was administered for 8 weeks and at the end of the treatment, the extensor digitorum longus (EDL) muscles were isolated and an isometric tension protocol was performed (repetitive electrical stimulation: pulses of 100 V, 300 ms duration and frequency 45 and 50 Hz, respectively). Treatment with apocynin contributed to a significant increase in the time of resistance to fatigue (88.23%; p <0.05) and improved the maximum muscle tension (72.23%; p <0.5) and total (80%; p <0.5) compared to the diabetic group. Additionally, a positive effect on weight and a decrease in blood glucose level was observed. Together, these results indicate that NOX2 inhibition exerted a protective effect on skeletal muscle tissue during diabetes.