Reversal of Lead-Induced Neuronal Apoptosis by Chelation Results in Rats: Role of Reactive Oxygen Species and Intracellular Ca2+

Lead, a ubiquitous and potent neurotoxicant causes several neurophysiological and behavioral alterations. Toxic properties of lead have been attributed to its capability to mimic calcium and alter calcium homeostasis. In this study, we have addressed the following issues: 1) whether chelation could circumvent the altered Ca2+ homeostasis and prevent neuronal death in chronic lead-intoxicated rats, 2) whether chelation could revert altered biochemical and behavioral changes, 3) whether combinational using two different chelating agents was more advantageous over mono in lead-treated rats, and 4) what could be the mechanism of neuronal apoptosis.
Results indicated that lead caused a significant increase in reactive oxygen species, neuronal nitric-oxide synthetase, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and altered bcl2/bax ratio indicated mitochondrial-dependent apoptosis. Most of these alterations reverted toward normal level following combination over mono with calcium disodium EDTA (CaNa2EDTA) or monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA). It could be concluded from our present results that combined with CaNa2EDTA and MiADMSA might be a better results protocol than mono with these chelators in lead-induced neurological disorders. We for the first time report the role of Ca2+ in regulating neurological dystrophy caused by chronic lead exposure in rats and its recovery with a two-course results regime of mono or combination .
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