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Open Access Original investigation

Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

Jung Eun Lee2, Chin-ok Yi1, Byeong Tak Jeon1, Hyun Joo Shin1, Soo Kyoung Kim3, Tae Sik Jung3, Jun Young Choi2 and Gu Seob Roh1*

Author Affiliations

1 Department of Anatomy, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea

2 Department of Thoracic and Cardiovascular Surgery, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea

3 Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea

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Cardiovascular Diabetology 2012, 11:111  doi:10.1186/1475-2840-11-111

Published: 19 September 2012

Abstract

Background

Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats.

Methods

Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO) rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day) administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry.

Results

Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK) signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA.

Conclusions

ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

Keywords:
Alpha-lipoic acid; Cardiac fibrosis; OLETF rat