The naturally occurring antioxidant lipoic acid (LA) was first described as an essential cofactor for the conversion of pyruvate to Acetyl-CoA, a critical step in respiration. LA is now recognized as a compound that has many biological functions. Along with its reduced form dihydrolipoic acid (DHLA), LA reduces and recycles cellular antioxidants such as glutathione, and chelates zinc, copper and other transition metal ions in addition to heavy metals. LA can also act as a scavenger of reactive oxygen and nitrogen species. By acting as an insulin mimetic agent, LA stimulates glucose uptake in many different cell types and can also modulate insulin signaling. The p38 and ERK MAP kinase pathways, AKT and NFκB are all regulated by LA. In addition, LA activates the prostaglandin EP2 and EP4 receptors to stimulate the production of the small molecule cyclic adenosine 5' monophosphate (cAMP). These diverse actions suggest that LA may be therapeutically effective in treating oxidative stress associated diseases. This review discusses the known biochemical properties of LA, its antioxidant properties, its ability to modulate signal transduction pathways, and the recent progress made in the utilization of LA as a therapeutic alternative for multiple sclerosis, Alzheimer's disease and diabetic neuropathy.
Biogerontology. 2006 Apr;7(2):111-8.
Oxidative stress and DNA single strand breaks in skeletal muscle of aged rats: role of carnitine and lipoicacid.
Sundaram K, Panneerselvam KS.
Department of Medical Biochemistry, Dr. AL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India, kumaransundaram@yahoo.com.
The exposure of biological system to various conditions of oxidative stress is the major contributor for aging process. Oxidative stress in turn increases the cellular levels of oxidatively modified proteins, lipids and nucleic acids resulting in a loss of physical activity and metabolic integrity. In this study, we evaluated the role of L-carnitine and DL-alpha-lipoic acid in minimizing oxidant generation and macromolecular damage in skeletal muscle of aged rats. We found that the oxidant generation was increased in aged rat skeletal muscle when compared to young rats. There was a simultaneous increase in the levels of lipid peroxidation, protein carbonyl content and DNA strand breaks in aged rat skeletal muscle. Administration of L-carnitine (300 mg/kg body wt/day) and DL-alpha-lipoic acid (100 mg/kg body wt/day) to aged rats for 30 days, decreased the oxidant generation, lipid peroxidation, protein carbonylation and DNA strand breaks. We concluded that co-administration of carnitine and lipoic acid to aged rats has the potential to prevent oxidative stress mediated macromolecular damage in skeletal muscle of aged rats by their putative role as efficient antioxidants.
PMID: 16802114 [PubMed - in process]
Arivazhagan P, Ayusawa D, Panneerselvam C.
Department of Biochemistry, Dr. ALM PGIBMS, University of Madras, Taramani Campus,
The purpose of the present investigation was to measure the activity of acetylcholinesterase in discrete regions of young and aged rat brain before and after DL-alpha-lipoic acid supplementation. Two groups of male albino rats were used in this study (4 and 24 months of age). DL-alpha-lipoic acid was administered intraperitoneally with a regimen of 100 mg/kg body weight per day using alkaline saline as a vehicle for 7 and 14 days. The activity was measured in the cerebral cortex, cerebellum, striatum, hippocampus and hypothalamus, and found to be significantly decreased in some of the brain regions in aged rats. Administration of lipoic acid into aged rats reversed the decrease in the activity in the discrete brain regions. These results suggest that lipoic acid is effective in restoration of the activity of acetylcholinesterase in aged rats.
PMID: 16706642 [PubMed - indexed for MEDLINE]
Puizina-Ivić N. Acta Dermatovenerol Alp Panonica Adriat. 2008 Jun;17(2):47-54.
Department of Dermatovenerology, Split Clinical Hospital Center, Soltanska 1, 21 000 Split, Croatia. neira@radogost.com
There are two main processes that induce skin aging: intrinsic and extrinsic. A stochastic process that implies random cell damage as a result of mutations during metabolic processes due to the production of free radicals is also implicated. Extrinsic aging is caused by environmental factors such as sun exposure, air pollution, smoking, alcohol abuse, and poor nutrition. Intrinsic aging reflects the genetic background and depends on time. Various expressions of intrinsic aging include smooth, thinning skin with exaggerated expression lines. Extrinsically aged skin is characterized by photo damage as wrinkles, pigmented lesions, patchy hypopigmentations, and actinic keratoses. Timely protection including physical and chemical sunscreens, as well as avoiding exposure to intense UV irradiation, is most important. A network of antioxidants such as vitamins E and C, coenzyme Q10, alpha-lipoic acid, glutathione, and others can reduce signs of aging. Further anti-aging products are three generations of retinoids, among which the first generation is broadly accepted. A diet with lot of fruits and vegetables containing antioxidants is recommended as well as exercise two or three times a week.