Abstract

Arsenic is a major threat to a large part of the population due to its carcinogenic nature. The toxicity of arsenic emerges from glutathione (GSH) depletion caused by arsenic with unknown mechanism. GSH depletion leads to apoptosis, lipid peroxidation and eventual cell death. The present study was designed to provide insight into the extent of changes in GSH level by arsenic. Plasma and cytosolic fraction were investigated for determination of changes in GSH metabolic status caused by arsenic in the form of arsenic trioxide (ATO). The depletion of GSH level was found to be positively correlated with increasing parameters, that is, arsenic concentration and time of incubation. Our findings show that changes in GSH status produced by arsenic could be due to adduct (As-(SG)₃) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of ATO. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity.

Key words: Arsenic trioxide (ATO), glutathione (GSH), dithiobisnitrobenzoic acid (DTNB), plasma, cytosolic fraction (C.F).