Alpha lipoic acid protects against dexamethasone-induced metabolic abnormalities via APPL1 and PGC-1 α up regulation

Background: Glucocorticoids (GCs) have various uses in the medicine in different specialties. However, GCs administration is usually accompanying with multiple side effects such as hyperglycemia and hyperlipidemia. Alpha lipoic acid (ALA) has been documented to posse anti-diabetic properties. Aim of the study: this study highlights the role of ALA in avoiding dexamethasone induced metabolic disturbance. Materials & Methods: 30 rats were randomly divided into 5 groups: Group (1): Control group; Groups 3, 4, and 5: rats received dexamethasone 1 mg/kg/day for 10 days; Groups 2, 4, and 5: Rats received ALA 100 mg/kg/day all the duration of the study, 2 weeks before dexamethasone, or concomitant with dexamethasone respectively. For each rat, we collected blood samples for measurement of glucose, lipid profiles, adiponectin, irisin, and Phosphoinositide 3-kinase (PI3K). We also isolated gastrocnemius muscles for measurement of insulin receptor substrate-1(IRS-1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC1-alpha), and adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1(APPL) gene expression. Results: Dexamethasone administration caused hyperglycemia, hyperlipemia, decrease the level of adiponectin, irisin, and PI3K besides decreasing the gene expression of IRS-1, PGC-1 alpha, and APPL1. ALA administration pre or concomitant to dexamethasone avoided these results. Conclusion: ALA can prevent metabolic abnormalities induced by dexamethasone via PGC1 alpha and APPL1 upregulation.