α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats

Abstract

α -lipoic acid (ALA) is an eight-carbon saturated fatty acid with strong antioxidant activity. Despite previous reports of ALA's protective properties in treating cardiovascular and metabolic diseases (including insulin resistance and diabetes), little is known about the compound's effects on skeletal muscle metabolism. In particular, the effect of ALA on glycooxidative and nitrosative damage in red muscles during insulin resistance is unknown. This study investigated the therapeutic potential of ALA on the antioxidant barrier as well as oxidative, nitrosative and carbonyl stress in the red skeletal muscle of rats with high-fat diet-induced insulin resistance. Male Wistar cmdb/outbred rats were divided into four equal groups: control diet (CTRL), high fat diet (HFD), CTRL + ALA (30 mg/kg body weight for 4 weeks; intragastrically) and HFD + ALA. Enzymatic and nonenzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory/apoptosis parameters were assessed using colorimetric, fluorimetric, and immune-enzymatic methods. ALA lowered body weight and glucose metabolism parameters in insulin-resistant rats. ALA not only strengthened enzymatic antioxidant defense (by increasing superoxide dismutase, catalase and glutathione peroxidase activity) but also stimulated the synthesis of non-enzymatic GSH. ALA supplementation inhibited lipid peroxidation (decreased lipid hydroperoxides and malondialdehyde content) and prevented protein oxidation (by lowering advanced oxidation protein products concentration) in red muscle. ALA's multifactorial actions on muscle tissue also included inhibition of inflammation and apoptosis, requiring further research to elucidate its effects in metabolic diseases.

Keywords: Alpha-lipoic acid; Antioxidant; Inflammation; Insulin resistance; Oxidative stress; Skeletal muscle.