Diabetes mellitus (DM) constitutes one of the public health problems today. It is characterized by hyperglycemia through a defect in the β-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study’s goal was to dissect the possible mechanisms by which apocynin could mediate its cardioprotective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A). DM was induced with streptozotocin. Apocynin treatment (3 mg/kg/day) was applied for 5 weeks. Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme activity was reduced in the D group compared to the C group; the apocynin treatment significantly attenuated these responses. In heart mitochondria, Complexes I and II of the electron transport chain (ETC) were significantly enhanced in the D+A group. Total glutathione, the level of reduced glutathione (GSH) and the GSH/ oxidized glutathione (GSSG) ratio were increased in the D+A group. Superoxide dismutase (SOD) and the glutathione peroxidase (GSH-Px) activities were without change. Apocynin enhances glucose uptake and insulin sensitivity, preserving the antioxidant defense and mitochondrial function.
Aims/Introduction Myopathy is a common complication of any diabetes type, consisting in failure to preserve mass and muscular function. Oxidative stress has been considered one of the main causes for this condition. This study aimed to search if Nicorandil, a KATP channel opener, could protect slow‐ and fast‐twitch diabetic rat muscles from oxidative stress, and to unveil its possible mechanisms. Materials and Methods Diabetes was induced in male Wistar rats by applying intraperitoneally streptozotocin (STZ) at 100 mg/kg doses. Nicorandil (3 mg/kg/day) was administered along 4 weeks. An insulin tolerance test and assessment of fasting blood glucose (FBG), TBARS, reduced (GSH), and disulfide (GSSG) glutathione levels, GSH/GSSG ratio, and mRNA expression of glutathione metabolism‐related genes were performed at end of treatment in soleus and gastrocnemius muscles. Results Nicorandil significantly reduced FBG levels and enhanced insulin tolerance in diabetic rats. In gastrocnemius and soleus muscles, Nicorandil attenuated the oxidative stress by decreasing lipid peroxidation (TBARS), increasing total glutathione and modulating GPX1‐mRNA expression in both muscle’s types. Nicorandil also increased GSH and GSH/GSSG ratio and downregulated the GCLC‐ and GSR‐mRNA in gastrocnemius, without significative effect on those enzymes’ mRNA expression in diabetic soleus muscle. Conclusions In diabetic rats, Nicorandil attenuates oxidative stress in slow‐ and fast‐twitch skeletal muscles by improving the glutathione system functioning. The underlying mechanisms for the modulation of glutathione redox state and the transcriptional expression of glutathione metabolism‐related genes seem to be fiber type‐dependent.
In response to diabetes mellitus, skeletal muscle is negatively affected, as is evident by reduced contractile force production, increased muscle fatigability, and increased levels of oxidative stress biomarkers. Apocynin is a widely used NADPH oxidase inhibitor, with antioxidant and anti-inflammatory potential. It has been effective for amelioration of a variety of disorders, including diabetic complications. Therefore, the present study was conducted to evaluate the effects and action mechanisms of apocynin in slow- and fast-twitch diabetic rat muscles. Male Wistar rats were rendered diabetic by applying intraperitoneally a single dose of streptozotocin (45 mg/kg). Apocynin treatment (3 mg/kg/day) was administered over 8 weeks. Fasting blood glucose (FBG), insulin tolerance and body weight gain were measured. Both slow (soleus) and fast (extensor digitorum longus, EDL) skeletal muscles were used for muscle function evaluation, oxidative stress markers, and evaluating gene expression using qRT-PCR. Treatment with apocynin significantly reduced FBG levels and enhanced insulin tolerance. Apocynin also prevented muscle contractile dysfunction in EDL muscle but had no significant effect on this parameter in soleus muscles. However, in both types of muscles, apocynin mitigated the oxidative stress by decreasing ROS levels and increasing total glutathione levels and redox state. Concomitantly, apocynin also statistically enhanced Nrf-2 and GLU4 mRNA expression and downregulated NOX2, NOX4, and NF-κB mRNA. Collectively, apocynin exhibits properties myoprotective in diabetic animals. These findings indicate that apocynin predominantly acts as an antioxidant in fast-twitch and slow-twitch muscles but has differential impact on contractile function.
Despite the known benefits of exercise training in reducing the hyperglycemic state and the harmful effects of Diabetes Mellitus on skeletal muscle health, the optimal exercise intensity to elicit maximal outcomes is still under debate. PURPOSE: To compare the effects of moderate-intensity training (MIT) with those of high intensity interval training (HIIT) sessions on glycemia and changes in GSH antioxidant system in slow-twitch and fast-twitch muscles of streptozotocin-induced diabetic rats. METHODS: Male Wistar rats (30 days old) were randomly divided into four groups: control (C), sedentary diabetic (SD), diabetic with HIIT (HIIT) and diabetic with MIT (MIT). Diabetes was induced by a single streptozotocin injection (100 mg/kg body weight), animals with fasting blood glucose levels ≥ 300 mg/dL were considered as diabetic. Exercise training programs were performed on a treadmill (30 minutes daily, 5 days/week) for 8 weeks. At the end of the intervention, extensor digitorum longus (EDL) muscle (fast-twitch) and soleus (slow-twitch) muscles were dissected and the concentration of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were determined. RESULTS: Exercise with MIT, but not HIIT, reduces blood glucose levels by 30.18% (p=0.001) compared to DS group. In diabetes, GSH concentrations were significantly lower in both muscles compared to C group. Both MIT and HIIT induced significant changes by increasing the total glutathione levels (GSH+GSSG) in slow (32.33% and 25.37%, respectively) and fast (188.15% and 156.38%, respectively) muscles compared SD group. However, only HIIT increases the GSH/GSSG ratio in slow muscle (107.36%), instead the MIT promoted greater benefits on fast muscles (55.89%) compared to SD group. CONCLUSIONS: Both exercise protocols have positive effects on GSH antioxidant system in slow-twitch and fast-twitch muscles, however, MIT appeared most effective to reduce diabetesrelated hyperglycemia.
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.
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