Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging.

BACKGROUND: Mitochondria are central to energy production and are therefore fully integrated into the rest of the cell's physiological responses to stress. The age-related decline of capacity of each cell to manufacture energy (as ATP) is due to the progressive loss of structural integrity of mitochondria. It is apparent that as the body ages, the cells become less and less able to maintain threshold levels of cellular energy production. METHODS: In the present study we have evaluated the efficacy of carnitine, a mitochondrial metabolite and lipoic acid, a potent antioxidant on the activities of the tri carboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase, Isocitrate dehydrogenase and electron transport complex I-IV in young and aged heart mitochondria. RESULT: We observed that there was an age-dependent decrement in the levels of the TCA cycle enzymes and electron transport chain complexes. Supplementation of carnitine (300 mg/kg bw/day) and lipoic acid (100 mg/kg bw/day) for 30 days brought the activities of these enzymes to almost near normal levels. CONCLUSION: These findings suggest that the combination of these drugs raises the mitochondrial energy producing capabilities by reversing the age-associated decline in mitochondrial enzyme activities and thereby protecting mitochondria from aging.

Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat.

Impaired antioxidant defense mechanisms and oxidative stress are implicated in the pathogenesis of arsenic toxicity. Our study was designed to determine whether alpha-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (70 mg/kg body weight) once daily for 60 days along with arsenic (100 ppm sodium arsenite mixed in drinking water) would prevent arsenic-induced changes in antioxidant defense system, superoxide dismutase (SOD-total SOD, Mn SOD, Cu/Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in rat brain regions such as cortex, hypothalamus, striatum, cerebellum and hippocampus. The present study also examined the effect of alpha-lipoic acid over arsenic-induced oxidant production and lipid peroxidation level (LPO) in discrete brain regions of rats. The cortex, striatum and hippocampus showed greater decreases in GSH-Px enzyme activity than cerebellum and hypothalamus with arsenic exposure. Striatum had the greatest percentage of decreased activities of total SOD and Mn SOD, whereas cortex had the greatest percentage decrease in the activity of Cu/Zn SOD in arsenic-alone treated rats. Hypothalamus and cerebellum exhibited the lowest catalase activity among all tested regions in arsenic-only treated rats. Rate of dichlorofluorescin oxidation, an indication of reactive oxygen species and other intracellular oxidants production was increased with arsenic exposure in all brain regions studied. Cortex, hippocampus and striatum exhibited greater increase of LPO levels than cerebellum and hypothalamus. SOD, CAT, GSH-Px activities were upregulated in arsenic plus lipoic acid treated versus arsenic-only treated rats. Also, simultaneous lipoic acid treatment along with arsenic proved to be sufficient in reducing oxidant production and LPO level in all rat brain regions. Our results demonstrate that arsenic-induced deficits in antioxidant enzyme activities and increase in oxidant production and lipid peroxidation level in brain regions can be overcome through simultaneous treatment with lipoic acid.