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Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy.
Chin Med J (Engl). 2009 Nov 05; 122(21):2580-6.CM

Abstract

BACKGROUND

Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant alpha-lipoic acid (alpha-LA) could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy.

METHODS

A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin (STZ) 45 mg/kg. Experimental animals were randomly assigned to 3 groups: normal control (NC), diabetes (DM) and DM treated with alpha-LA (alpha-LA). The latter group was administered with alpha-LA (100 mg/kg ip per day), the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde (MDA), reduced glutathione (GSH) and the activity of manganese superoxide diamutase (Mn-SOD) in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting.

RESULTS

At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the alpha-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by alpha-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while alpha-LA reversed this structural derangement. The index of cardiac function (+/-dp/dtmax) in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but alpha-LA delayed deterioration of cardiac function (P < 0.05).

CONCLUSIONS

Our findings indicate that the antioxidant alpha-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of alpha-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.

Authors+Show Affiliations

The Ministry of Health Key Laboratory of Hormone and Development, Department of Endocrinology, Metabolic Disease Hospital of Tianjin Medical University, Tianjin 300070, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19951573

Citation

Li, Chun-jun, et al. "Attenuation of Myocardial Apoptosis By Alpha-lipoic Acid Through Suppression of Mitochondrial Oxidative Stress to Reduce Diabetic Cardiomyopathy." Chinese Medical Journal, vol. 122, no. 21, 2009, pp. 2580-6.
Li CJ, Zhang QM, Li MZ, et al. Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Chin Med J (Engl). 2009;122(21):2580-6.
Li, C. J., Zhang, Q. M., Li, M. Z., Zhang, J. Y., Yu, P., & Yu, D. M. (2009). Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Chinese Medical Journal, 122(21), 2580-6.
Li CJ, et al. Attenuation of Myocardial Apoptosis By Alpha-lipoic Acid Through Suppression of Mitochondrial Oxidative Stress to Reduce Diabetic Cardiomyopathy. Chin Med J (Engl). 2009 Nov 5;122(21):2580-6. PubMed PMID: 19951573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. AU - Li,Chun-jun, AU - Zhang,Qiu-mei, AU - Li,Ming-zhen, AU - Zhang,Jing-yun, AU - Yu,Pei, AU - Yu,De-min, PY - 2009/12/3/entrez PY - 2009/12/3/pubmed PY - 2010/3/5/medline SP - 2580 EP - 6 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 122 IS - 21 N2 - BACKGROUND: Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant alpha-lipoic acid (alpha-LA) could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. METHODS: A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin (STZ) 45 mg/kg. Experimental animals were randomly assigned to 3 groups: normal control (NC), diabetes (DM) and DM treated with alpha-LA (alpha-LA). The latter group was administered with alpha-LA (100 mg/kg ip per day), the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde (MDA), reduced glutathione (GSH) and the activity of manganese superoxide diamutase (Mn-SOD) in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting. RESULTS: At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the alpha-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by alpha-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while alpha-LA reversed this structural derangement. The index of cardiac function (+/-dp/dtmax) in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but alpha-LA delayed deterioration of cardiac function (P < 0.05). CONCLUSIONS: Our findings indicate that the antioxidant alpha-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of alpha-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria. SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/19951573/Attenuation_of_myocardial_apoptosis_by_alpha_lipoic_acid_through_suppression_of_mitochondrial_oxidative_stress_to_reduce_diabetic_cardiomyopathy_ L2 - https://Insights.ovid.com/pubmed?pmid=19951573 DB - PRIME DP - Unbound Medicine ER -