title: Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium: Interception by naringenin.
abstract: 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.
authors: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, Jamia Hamdard, New Delhi, India.
authors: F
authors: F
authors: Ali
authors: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, Jamia Hamdard, New Delhi, India.
authors: A Q
authors: AQ
authors: Khan
authors: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, Jamia Hamdard, New Delhi, India.
authors: R
authors: R
authors: Khan
authors: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, Jamia Hamdard, New Delhi, India sarwat786@rediffmail.com.
authors: S
authors: S
authors: Sultana
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004734:Energy Metabolism / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012997:Solvents / Q000633:toxicity*; D014241:Trichloroethylene / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D044950:Flavanones; D005609:Free Radicals; D016328:NF-kappa B; D012997:Solvents; D014241:Trichloroethylene; D011493:Protein Kinase C; C005273:naringenin; D002118:Calcium
keywords: COX-2; NF-κB; PKC; TCE; calcium ions; naringenin