Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8545883 | Environmental Toxicology and Pharmacology | 2018 | 5 Pages |
Abstract
Chlorothalonil, a polychlorinated aromatic fungicide, is considered non-toxic to small mammals. However, chlorothalonil inactivates sulfhydryl enzymes and depletes cellular glutathione. Chlorothalonil increases intracellular Zn2+ concentration ([Zn2+]i) in mammalian cells possibly because intracellular Zn2+ is released via zinc-thiol/disulfide interchange. The effects of chlorothalonil at sublethal concentrations on the cellular content of nonprotein thiols ([NPT]i) and [Zn2+]i were examined using flow cytometry in rat thymocytes. Low concentrations (0.3-1â¯Î¼M) of chlorothalonil increased, but high concentrations (3-10â¯Î¼M) decreased [NPT]i. These effects of chlorothalonil were partly attenuated by an intracellular Zn2+ chelator. Chlorothalonil at 0.3-10â¯Î¼M increased [Zn2+]i in a concentration-dependent manner, which was largely dependent on the release of intracellular Zn2+. Both the decrease in [NPT]i and increase in [Zn2+]i increase the vulnerability of cells to oxidative stress. Chlorothalonil at 1-10â¯Î¼M potentiated the cytotoxicity of H2O2 (300â¯Î¼M). It was also the case for 10â¯Î¼M pentachloronitrobenzene, but not 10â¯Î¼M pentachlorophenol. In conclusion, chlorothalonil at low (sublethal) micromolar concentrations is cytotoxic to mammalian cells under oxidative stress.
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Authors
Mizuki Ikeda, Junji Deguchi, Shota Fukushima, Ai Qingyu, Norihiro Katayama, Hajime Miura, Yasuo Oyama,