Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium: Interception by naringenin.
Industrial solvents pose a significant threat to the humankind. The mechanisms of their toxicity still remain in debate. Trichloroethylene (TCE) is a widespread industrial solvent responsible for severe liver dysfunction, cutaneous toxicity in occupationally exposed humans. We utilized an in vitro system of human epidermal keratinocyte (HaCaT) cells in this study to avoid complex cell and extracellular interactions. We report the cytotoxicity of organic solvent TCE in HaCaT and its reversal by a natural flavanone, naringenin (Nar). The cytotoxicity was attributed to the rapid intracellular free calcium (Ca(2+)) release, which might lead to the elevation of protein kinase C along with robust free radical generation, instability due to energy depletion, and sensitization of intracellular stress signal transducer nuclear factor κB. These effects were actually seen to induce significant amount of genomic DNA fragmentation. Furthermore, all these effects of TCE were effectively reversed by the treatment of Nar, a natural flavanone. Our studies identify intracellular Ca as a unique target used by organic solvents in the cytotoxicity and highlight the Ca(2+) ion stabilizer properties of Nar.
['Ali|F|F|', 'Khan|A Q|AQ|', 'Khan|R|R|', 'Sultana|S|S|']
D002118:Calcium D002460:Cell Line D002470:Cell Survival D053938:DNA Fragmentation D004734:Energy Metabolism D000078404:Epidermal Cells D004817:Epidermis D044950:Flavanones D005609:Free Radicals D006801:Humans D015603:Keratinocytes D053078:Membrane Potential, Mitochondrial D016328:NF-kappa B D011493:Protein Kinase C D012997:Solvents D014241:Trichloroethylene
naringenin TCE COX-2 NF-κB PKC calcium ions