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Toxicol Lett. 2002 Nov 15;136(1):65-76.

Apoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidants.

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Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India.


Epidemiological studies on arsenic contamination in drinking water indicated presence of arsenic in fetal tissues. Experiments on human fetal brain explants on exposure to arsenic in culture showed disturbance in lipid peroxidation, generation of nitric oxide (NO), reactive oxygen species (ROS) and apoptosis. The oxidative stress challenged by antioxidant vitamins C, E or chelator dimercaptosuccinic acid (DMSA) may reverse arsenic toxicity on neuronal development. The concept was tested with the models: (A) human fetal brain explants exposed to arsenic, 0.3 mg/l in culture for 24 h; (B) rat neonatal brain explants from 1-day-old litters exposed to 0.3 mg/l arsenic in drinking water during gestation. Rats (n=10) were given oral administration of vitamin C, 2.5 mg/kg/day, vitamin E, 148 microg/kg/day during gestation and DMSA, 50 mg/kg for 2 days at the end of gestation. (A) The arsenic induced in human fetal brain explants increase in production of NO, 20% and ROS, 25%, and decrease in DNA, 62% and protein, 54% synthesis. The morphological analyses showed growth of viable cells, neural networking vis-à-vis apoptosis on exposure to arsenic for 24 h and necrosis and loss of ground matrix on arsenic exposure for 18 days. The occurrence of two processes of apoptosis and necrosis in different neurons of same culture indicated existence of a selective cellular defense against arsenic toxicity. (B) The rats exposed to arsenic showed increased generation of NO, 25% and ROS, 22%, loss of glutathione content from 42 to 35 microg/mg protein, 40% increase in lipid peroxidation and decreased superoxide dismutase at 32%. The administration of vitamins C, E and DMSA showed partial reversal of the effects indicating possible protection from arsenic toxicity.

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