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

Abstract

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

Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity

“…Although the ameliorative effects of LA, Resveratol and Quercetin on cardiac oxidative stress has been demonstrated in past studies [35][36][37], the mechanisms have only been partially explained. In this study, the reduced antioxidant capacity in obese mice…”

“…Persistent inhibition of GSK3β induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility by suppressing mPTP opening [34]. Given the pivotal role of natural antioxidants in redox regulation, and considerable evidence supporting their ameliorative effects on oxidative stress [35][36][37], current interest is on mechanisms for their cardio-protection. Therefore, the objective of this study was to examine the possible mechanisms for protective effects of Lipoic acid (LA), Quercetin and Resveratrol on oxidative stress induced injury on the heart of obese C57BL/6 mice.…”

Quantitative proteomics study of protective effects of grape seed procyanidin B2 on diabetic cardiomyopathy in db/db mice

“…14) Cardiac fibrosis may cause myocyte hypertrophy and deranged myofibrils, which resulting from oxidative stress, AGEs, cellular growth and proliferation, inflammation, and some involved mediators. 15,16) However, effective treatments of diabetic cardiomyopathy are not available. Thus, identifying the biomarkers involved in cardiac fibrosis may provide novel therapeutic targets for reducing the detrimental effects of diabetes.…”

Alpha-lipoic acid attenuates cardiac hypertrophy via inhibition of C/EBPβ activation

“…Collective evidence confirmed that ALA is involved in mitochondrial dehydrogenase reactions and has recently gained a considerable amount of attention as a novel antioxidant (Li et al, 2012). ALA has also been regarded as a therapeutic agent for a number of conditions related to cardiovascular disease, including atherosclerosis (Xu et al, 2012), diabetic cardiomyopathy (Hegazy et al, 2013), cardiac fibrosis (Lee et al, 2012). Dietary supplementation with ALA has been successfully employed in a variety of in vivo models: ischemia-reperfusion, heart failure, and hypertension (Ghibu et al, 2009).…”