Mitochondrial protective and antioxidant agents protect toxicity induced by depleted uranium in isolated human lymphocytes

Abstract

Depleted uranium (DU) is a by-product of the enrichment procedure of natural uranium. During production and usage, uranium may be released into the environment due to failure to follow standard procedures, thus causing environmental pollution. In this study, toxicity effects of uranium (VI) and protective role of mitochondrial permeability transition pore sealing and antioxidant agents studied by isolated human lymphocytes. Human lymphocytes were exposed to different concentrations (0.1, 0.5, 1, 2 and 5 mM) of DU for 6 h and cytotoxicity was measured by trypan blue assay. The mechanistic parameters were assessed after 1, 2 and 3 h of lymphocyte treatment with 1/2 IC506h (0.3 mM), IC506h (0.8 mM) and 2 IC506h (1.6 mM) of DU. The reactive oxygen species (ROS), lysosomal membrane destabilization, mitochondrial membrane potential (MMP), lipid peroxidation, GSH and GSSG levels on human lymphocytes exposed to UA, were measured. The results indicate that toxicity of U (VI) was concentration dependent on human lymphocytes. Also, U (VI) induced ROS production, MMP reduction, lysosomal membrane destabilization and lipid peroxidation in human lymphocytes. In U (VI) treated lymphocytes, decrease in intracellular GSH and raise in extracellular GSSG levels were observed. We report that mitochondrial permeability transition (MPT) pore sealing and antioxidant agents, have the capacity significantly to prevents, mitochondrial toxicity. Thus, the inhibition of mitochondrial oxidative stress and mitochondrial dysfunction by MPT pore sealing and antioxidant agents is associated with the inhibition of DU-induced mitochondrial damages and activation of apoptosis in lymphocytes.