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