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.
Shila
S
S
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Kokilavani
V
V
Subathra
M
M
Panneerselvam
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001151:Arsenic / Q000032:analysis / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry; D002374:Catalase / Q000378:metabolism; D005452:Fluoresceins; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D000975:Antioxidants; D005452:Fluoresceins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014874:Water Pollutants, Chemical; C037631:2',7'-dichlorofluorescein; D008063:Thioctic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001151:Arsenic