Metabolic modulation of glutathione in whole blood components against lead-induced toxicity

Abstract

Lead has been found to have the ability to interfere in the metabolism and biological activities of many proteins. It has also been found that metalloelements have strong affinity for sulfhydryl (-SH) groups in biological molecules including glutathione (GSH) in tissues. Because of these facts, it was of interest to investigate further the interaction of lead acetate [Pb (CH₃COO)₂] with GSH as a biomarker of toxicity and the role of GSH in the detoxification and conjugation processes in whole blood components. Effects of different concentrations of Pb(CH₃COO)₂ on the level of reduced GSH in whole blood components (plasma and cytosolic fraction) were examined. GSH depletion in whole blood components was lead acetate concentration dependent. Depleted GSH level was however more pronounced with time. These findings show that changes in the GSH status produced by Pb(CH₃COO)₂ could be due to either by adduct (Pb-SG) formation or by increased production of oxidized glutathione (2GSH ^Pb+2 GSSG). This change in GSH metabolic status provides information regarding the mechanism of toxicity of Pb(CH₃COO)₂. These findings are therefore important for the rational design of antidote against  the prevention of lead induced toxicity.

Key words: Lead acetate, glutathione (GSH), dithiobisdinitrobenzoic acid (DTNB), plasma and cytosolic fraction (CF).