The Protective Effect Of Alpha-Lipoic Acid On Mitochondria In The Kidney Of Diabetic Rats

Background: Diabetic nephropathy (DN) is one of the most common chronic complications of diabetes and the leading cause of end-stage renal disease. Recent research has found that oxidative stress participates in the development of diabetic nephropathy. alpha-lipoic acid (alpha-LA), a powerful antioxidant, plays an important role in renal protection against DN, but the underlying mechanism remains unknown. This study modeled the renal protective effects of alpha-lipoic acid in streptozotocin (STZ) induced diabetic rats and explore the underlying mechanism, which provides new theoretical bases for clinical treatment of diabetic nephropathy. Methods: The diabetic model was induced by intraperitoneal injection of STZ on Male SD and then the diabetic rats were randomly divided into two groups: untreated-diabetic group (DM group), alpha-LA treated-diabetic group (alpha-LA group), and the normal rats served as control group (NC group). After 8 weeks of STZ induction, Blood glucose (BG), Blood Urea Nitrogen (BUN), Serum Creatinine (SCr) and urinary albumin excretion rate (UAER) were examined, and morphological changes were assessed by histology. The levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) were also evaluated in serum and renal cortex. Additionally, kidney mitochondrial membrane potential and mitochondrial swelling were measured for different groups. The expression of voltage-dependent anion channel (VDAC) on mitochondria were evaluated by both Western blotting and Immunohistochemistry. Results: After 8 weeks induction of STZ, significant reductions in BUN, SCr, UAER (P<0.01 or P<0.05) and histological improvement were observed in the alpha-LA group compared to the DM group. In the serum and renal cortex of alpha-LA group, the content of MDA and the activities of SOC were both significantly decreased (P<0.05). Compared to the DM group, the mitochondrial membrane potential in the alpha-LA group was significantly increased (P<0.05) and mitochondrial swelling was reduced. Meanwhile, the expression of VDAC on mitochondrial was significantly increased (P<0.05) in the alpha-LA group. Conclusion: Our findings indicate that antioxidant alpha-LA exerts a protective role against the development of DN, and the underlying mechanism may involve effective suppression of the generation of oxidants, protection of mitochondrial function, and up-regulating of VDAC expression.