Investigation of effects of alpha-lipoic acid and quercetin on diaphragm function in streptozotocin-induced diabetic rat model

Diabetes mellitus is a metabolic disease characterized by changes in glucose, lipid and amino acid metabolism, leading to chronic complications that also affect the respiratory system. This study aimed to investigate the effects of α-lipoic acid (ALA) and quercetin (QUE) on diaphragm muscle contraction in streptozotocin (STZ)-induced diabetic rats. The diaphragm is a muscle that plays an important role in respiration, and the study was investigated how diabetes affects the function of this muscle and the relationship of this effect with oxidative stress. A total of 83 male Sprauge Dawley rats (8-10 weeks old) were used in the study. After diabetes was induced with STZ, rats were divided into 13 groups and intraperitoneally saline, sodium bicarbonate, ALA (30, 60 and 120 mg/kg), QUE (30, 60 and 120 mg/kg), and subcutaneous insulin (8 IU/kg) were administered for eight weeks. In addition, ALA (30, 60, 120 mg/kg) was administered subcutaneously in combination with insülin. The biomechanical properties of the diaphragm were determined by applying electrical field stimulation to the diaphragm muscle preparation in the isolated organ bath system. Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured to determine the oxidative stress in the diaphragm tissue. Compared to the control group, all diabetic groups showed a significant reduction in maximum contraction and tetanic contraction forces in the diaphragm (p<0.05). The administration of 120 mg/kg ALA in combination with insulin increased maximum contraction response and tetanic contraction force in the diaphragm of diabetic rats (p<0.05). ALA and QUE applications decreased the high MDA level in diabetic animals (p<0.05). ALA and QUE applications increased the CAT and GPx activities, which were found to be low in diabetic animals (p<0.05). As a result, it was determined that STZ-induced diabetes negatively affected the biomechanical functions of the diaphragm and caused a decrease in contraction force. It was observed that 120 mg/kg ALA administered in combination with insulin significantly improved diaphragm muscle performance. It is thought that ALA may be a potential treatment to reduce the negative effects of diabetes on muscle and oxidative stress. Therefore, we suggest that approaches targeting oxidative stress in diabetes treatment may have long-term positive effects on respiratory muscle function. Keywords: Alpha-lipoic acid, Diabetes Mellitus, Diaphragm, Quercetin, Streptozotocin