Alpha-lipoic acid: mechanisms of action and beneficial effects in the prevention and treatment of diabetic complications

Abstract

Alpha-lipoic acid (ALA) has been widely prescribed drug for treatment and prevention of diabetic complications since it affects the main pathogenesis links. ALA has many biochemical functions acting as a biological antioxidant, anti-inflammatory properties, metal chelators, reducing the oxidized forms of other antioxidant agents such as vitamin C and E and glutathione, and modulating the signaling transduction of several pathways, like insulin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). ALA can protect albumin from glycation, improves the redox state of the plasma and endothelium-dependent vasodilation; induces protein kinase B phosphorylation in vascular endothelial cells; shows a protective effect on oxidative stress-induced apoptosis. In skeletal muscle ALA reduce triglyceride accumulation, enhances expression of the insulin receptor substrate 1 protein and improves insulin sensitivity by activating 5′-AMP-activated protein kinase, recruits glucose transporter type 4 from its storage site in the Golgi to the sarcolemma. Prescription of ALA can have both detrimental and cytoprotective effects on pancreatic β-cells.

Role of Alpha Lipoic Acid in Ameliorating the Histological Alterations of Pituitary-Testicular Axis –induced by Hydrogen Peroxide in Rats

“…Testicular sections of rats received ALA had normal seminiferous tubules with complete spermatogenesis and normal interstitial connective tissue figures (13, 14,) in comparison to control figure (15,16). H2O2 treated rats group T2 exhibited histopathological alterations in thewith degenerative changes of majority of seminiferous tubules characterized with incomplete spermatogenesis and edema figure (17 ). Besides the majority of seminiferous tubules were almost devoid of spermatids and spermatozoa with vacuolar degeneration of spermatogonia , Sertoli cells and Leydigs cells which evoked on cessation of spermatogenesis figures (18,19) .…”

“…It has been reported that ALA have powerful antioxidant abilities, equal to that of coenzyme Q 10, vitamin C, and vitamin E (16). Unlike other antioxidants, ALA alpha lipoic acid has ability to neutralize free radicals in intracellular and extracellular environments (17).…”

Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats

“…The mechanisms involved in the protective effects against lead and zinc oxide nanoparticles can be postulated depending on the previous studies. ALA improves the redox state of the plasma and shows a protective effect on oxidative stress-induced apoptosis (Serhiyenko et al, 2018). One study of α-LA against hydrogen peroxide-induced toxicity in human lymphocytes showed it to be an ideal compound that has profound protective effects on oxidation, inflammation, and apoptosis (Rahimifard et al, 2015).…”

Alpha-lipoic acid and diabetic cardiac autonomic neuropathy

“…Stimulating adenosine monophosphate-activated protein kinase, with each of these components having numerous consequences. 21,26,36,37 The positive influences of ALA on such metabolic and functional parameters are partly confirmed by its neurotropic, cardioprotective, angioprotective and cytoprotective properties; this finding suggests its usefulness in the treatment of T2D patients with diabetic cardiac autonomic neuropathy.…”