Effects of Alpha-lipoic Acid on Nitric Oxide Synthase Expression and Ultrastructural Changes in the Bladder of Rats with Streptozotocin-induced Diabetes.
10.4111/kju.2007.48.2.212
- Author:
Dong Il KANG
1
;
Sun Hyun KIM
;
Sang Don LEE
;
Ho Sup KWAK
;
Sung Hyup CHOI
;
Do Ri KIM
;
Kweon Sik MIN
Author Information
1. Department of Urology, Inje University College of Medicine, Korea. kweonsikmin@ medimail.co.kr
- Publication Type:Original Article
- Keywords:
Antioxidants;
Bladder;
Diabetes mellitus;
Oxidative stress
- MeSH:
Animals;
Antioxidants;
Diabetes Mellitus;
Humans;
Injections, Intraperitoneal;
Male;
Mitochondria;
Muscle Cells;
Myocytes, Smooth Muscle;
Nitric Oxide Synthase*;
Nitric Oxide*;
Oxidative Stress;
Rats*;
Rats, Sprague-Dawley;
Thioctic Acid*;
Urinary Bladder*
- From:Korean Journal of Urology
2007;48(2):212-218
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: To evaluate whether alpha-lipoic acid (ALA) is effective at restoring the levels of nitric oxide synthase (NOS) expression and preventing ultrastructural changes in the bladder of rats with streptozotocin- induced diabetes. MATERIALS AND METHODS: Nine-week-old male Sprague-Dawley rats were used. The experimental groups included a control group (n=6), a diabetes group (n=6), and two groups of diabetic rats treated with intraperitoneal injections of ALA (n=12) at either 50 (ALA50) or 100mg/kg/day (ALA100) for 8 weeks after the induction of diabetes. Diabetic oxidative stress was determined based on evaluation of immunohistochemical staining for 8-hydroxy-2-deoxyguanosine (8-OHdG). The measurements of the levels of eNOS and nNOS expressions, as well as an assessment of the ultrastructural changes in detrusor smooth muscle cells were performed. RESULTS: The highest expression of 8-OHdG was observed in the diabetes group; whereas, the 8-OHdG expression in the ALA-treated groups was similar to that in the control group. Both eNOS and nNOS were constitutively expressed in the control group. The expression levels of both eNOS and nNOS proteins were higher in the diabetes group, which had experienced increased oxidative stress, than in the ALA50 and ALA100 groups. Compared with the control group, the diabetes group exhibited severe degeneration of the detrusor muscle cells. In the rats treated with ALA, the detrusor muscle cells showed mild to moderate degeneration. The mean numbers of mitochondria per smooth muscle cell in the control, diabetes, ALA50 and ALA100 groups were 12.6+/-1.5, 5.1+/-0.7, 18.3+/-0.7 and 19.3+/-1.3, respectively (p<0.01). CONCLISIONS: Our data suggest that diabetes enhanced the levels of eNOS and nNOS expressions in the bladder, and ALA inhibited the expressions of eNOS and nNOS. ALA had a protective effect against the degeneration of intracellular micro-organelles produced by diabetic oxidative damage in detrusor muscle cells. This study suggests that early treatment with ALA can reduce the damage caused by diabetic oxidative stress.
