Chronic Treatment with α-Lipoic Acid Improves Endothelium-Dependent Vasorelaxation of Aortas in High-Fat Diet-Fed Mice

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  • Takenouchi Yasuhiro
    Department of Pharmacology, Kawasaki Medical School Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University
  • Tsuboi Kazuhito
    Department of Pharmacology, Kawasaki Medical School
  • Ohsuka Kenji
    Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University
  • Nobe Koji
    Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University
  • Ohtake Kazuo
    Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University
  • Okamoto Yasuo
    Department of Pharmacology, Kawasaki Medical School
  • Kasono Keizo
    Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University

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Abstract

<p>α-Lipoic acid (ALA) is used as a dietary supplement and known as an anti-oxidant. The present study aimed to examine whether ALA improves endothelial dysfunction in high-fat diet-fed obese mice. After feeding a high-fat diet to Institute of Cancer Research (ICR) mice for 4 weeks, the mice were maintained with a high-fat diet (group HF) or a high-fat diet containing ALA (25 mg/d, group HF + ALA) for an additional 20 weeks. Age-matched normal diet-fed mice were also used (group Normal). Chronic oral treatment with ALA did not affect various plasma parameters or body weights. As compared with the aortas of Normal mice, those from HF mice showed impaired endothelium-dependent relaxation in response to clonidine. However, such an impairment was not observed in the aortas from HF + ALA mice. The plasma levels of thiobarbituric acid reactive substances, an indicator of oxidative stress, were significantly decreased in HF + ALA mice compared with HF mice, confirming the anti-oxidative effects of ALA. In addition, when the impaired clonidine-induced vasorelaxation of aortas from normal mice under high glucose conditions was used as a model of acute oxidative stress, the vasorelaxation responses were improved in the presence of ALA at 100 µM. Our results suggested that the chronic oral administration of ALA improves endothelial dysfunction in high-fat diet-fed obese mice possibly through the reduction in oxidative stress in vivo.</p>

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