IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2013;6(2):90-97

Original Article
The protective effect of α-Lipoic acid on mitochondria in the kidney of diabetic rats
Li Wang, Chen-Guang Wu, Chun-Qian Fang, Jing Gao, Ying-Zhao Liu, Yan Chen, Yu-Ning Chen, Zhi-Gang Xu

Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, China; College of
Pharmacy, Jiangsu University, Zhenjiang Jiangsu 212013, China

Received November 26, 2012; Accepted January 5, 2013; Epub January 26, 2013; Published February 6, 2013

Abstract: 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. α-lipoic acid (α-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 α-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), α-LA treated-diabetic group (α-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 α-LA group compared to the DM group. In the serum and renal cortex of α-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 α-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 α-LA group. Conclusion: Our findings indicate that antioxidant α-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. (IJCEM1211005).

Keywords: Diabetic nephropathy, reactive oxygen species, mitochondria, voltage-dependent anion channel, α-lipoic acid

Address correspondence to: Dr. Chen-Guang Wu, Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu
University, Zhen-jiang 212002, China. Phone: 13852943288; E-mail: Wcgzj1128@yahoo.com.cn