Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases

Abstract

Alpha-lipoic acid is a naturally occurring substance, essential for the function of different enzymes that take part in mitochondria’s oxidative metabolism. It is believed that alpha-lipoic acid or its reduced form, dihydrolipoic acid have many biochemical functions acting as biological antioxidants, as metal chelators, reducers of the oxidized forms of other antioxidant agents such as vitamin C and E, and modulator of the signaling transduction of several pathways. These above-mentioned actions have been shown in experimental studies emphasizing the use of alpha-lipoic acid as a potential therapeutic agent for many chronic diseases with great epidemiological as well economic and social impact such as brain diseases and cognitive dysfunctions like Alzheimer disease, obesity, nonalcoholic fatty liver disease, burning mouth syndrome, cardiovascular disease, hypertension, some types of cancer, glaucoma and osteoporosis. Many conflicting data have been found concerning the clinical use of alpha-lipoic acid in the treatment of diabetes and of diabetes-related chronic complications such as retinopathy, nephropathy, neuropathy, wound healing and diabetic cardiovascular autonomic neuropathy. The most frequent clinical condition in which alpha-lipoic acid has been studied was in the management of diabetic peripheral neuropathy in patients with type 1 as well type 2 diabetes. Considering that oxidative stress, a imbalance between pro and antioxidants with excessive production of reactive oxygen species, is a factor in the development of many diseases and that alpha-lipoic acid, a natural thiol antioxidant, has been shown to have beneficial effects on oxidative stress parameters in various tissues we wrote this article in order to make an up-to-date review of current thinking regarding alpha-lipoic acid and its use as an antioxidant drug therapy for a myriad of diseases that could have potential benefits from its use.Electronic supplementary materialThe online version of this article (doi:10.1186/1758-5996-6-80) contains supplementary material, which is available to authorized users.

Protective effects of alpha lipoic acid on high glucose-induced neurotoxicity in PC12 cells

“…ALA rapidly crosses the cell membranes, cytosol and blood-brain barrier. Due to amphiphilic properties, ALA has more advantages compared with other antioxidants such as vitamin C and E. Interestingly, Lipoic acid and its reduced form, dihydrolipoic acid (DHLA) has a redox potential of −0.32 V while the redox potential of GSH/ GSSG is −0.24 V. This difference reflects the fact that ALA has a greater defense capacity against oxidative damage than does GSH and ALA is able to reduce oxidized glutathione to GSH (Dwivedi et al 2014;Gomes and Negrato 2014;Rochette et al 2013;Smith et al 2004). It displays antioxidant effects by scavenging ROS and regenerates other endogenous oxidized antioxidants to their active reduced form (Hussein et al 2012).…”

Beneficial Effect of Bis(Hinokitiolato)Zn Complex on High-fat Diet-induced Lipid Accumulation in Mouse Liver and Kidney

“…Numerous researchers have reported the effects of many organic or inorganic compounds on various organs, leading to disorders such as fatty liver or diabetic nephropathy (5,6). Furthermore, other studies have reported that some compounds, even known as beneficial food materials, can worsen a disease condition (7,8).…”

Alpha-lipoic acid in treatment of diabetes mellitus complications

“…Перші випадки терапевтичного застосування α-ЛК описали 1959 року в Німеччині E. Bock та J. Schneeweiss -для лікування хворих із гострим отруєнням грибами Аmanita phalloides. А невдовзі ті самі автори виявили лікувальні властивості α-ЛК при невропатіях [1].…”

“…У наш час α-ЛК та її відновленій хімічній формі -дигідроліпоєвій кислоті приписують низку корисних біохімічних та епігенетичних властивостей: вони діють як універсальні антиоксиданти, здатні відновлювати окислені форми інших ферментів антиоксидантного захисту організму, а також модулюють численні внутрішньоклітинні сигнальні шляхи, зокрема інсуліновий та ядерний фактор каппа В (NFkB) [1,2]. Перераховані властивості, а також безпека α-ЛК як ендогенного метаболіту організму людини обгрунтовують напрямок вивчення препаратів на її основі при лікуванні захворювань, у патогенезі яких важливу роль відіграють оксидантний стрес, інсулінорезистентність та системна запальна відповідь, зокрема -цукрового діабету (ЦД) та його ускладнень.…”

“…Вважається, що основними рушійними факторами є хронічна гіперглікемія, інсулінорезистентність тканин, оксидантний стрес, та порушення кровопостачання органів-мішеней, зумовлені мікроангіопатією [1]. Оксидантний стрес призводить до порушень у сигнальних ланцюжках багатьох внутрішньоклітинних процесів.…”