Molecular mechanism in pathogenesis of arsenic intoxication-toward forensic molecular toxicological clarification-

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We analyzed pathophysiological roles of inflammatory cytokine, IL-6, and female sex hormone, estrogen, in arsenite-induced renal injury by using mouse models. We found a crucial involvement of autophagic cell death of renal tubular epithelial cells in pathogenesis of arsenite-induced renal injury. We clarified that IL-6 played a protective role in pathogenesis of arsenite-induced renal injury by reduction of autophagy through suppression of ERK phosphorylation. We also found a gender difference in susceptibility to renal toxicity of arsenite, which was caused by an interference of IL-6/Stat3 signaling by estrogen.