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Issue 2, 2018
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Mitochondrial toxicity of organic arsenicals: membrane permeability transition pore opening and respiratory dysfunction

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Abstract

In order to clarify the mitochondrial toxicity mechanism of the organic arsenical MOPIMP (2-methoxy-4-(((4-(oxoarsanyl) phenyl) imino) methyl) phenol), research was carried out at the sub-cell level based on the previous finding that the compound MOPIMP can damage the mitochondria by triggering a burst of ROS. After investigating its influence on isolated mitochondria in vitro, it was demonstrated that a high dose of MOPIMP with short-term exposure can induce mitochondrial swelling, decrease the membrane potential, enhance the permeability of H+ and K+, and induce membrane lipid peroxidation, indicating that it can result in an MPT process in a ROS-mediated and Ca2+-independent manner. Additionally, MPT was also aggravated as a result of impairment of the membrane integrity and membrane fluidity. In addition, short-term incubation between mitochondria and compound MOPIMP promoted the inhibition of respiratory chain complexes I, II, III and IV, as well as damage to the respiration process, which supported the previous finding about the burst of ROS. On the other hand, after long-term exposure by the organic arsenical MOPIMP, mitochondrial metabolic dysfunction was triggered, which was in accordance with perturbation of the respiratory chain complexes as well as the respiration process. This work systematically sheds light on the mitochondrial toxicity mechanism of the organic arsenical MOPIMP, including induction of the MPT process and inhibition of respiratory metabolism, which provides a potential target for organic arsenicals as anti-tumor drugs.

Graphical abstract: Mitochondrial toxicity of organic arsenicals: membrane permeability transition pore opening and respiratory dysfunction

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Publication details

The article was received on 30 Aug 2017, accepted on 22 Nov 2017 and first published on 19 Dec 2017


Article type: Paper
DOI: 10.1039/C7TX00234C
Citation: Toxicol. Res., 2018,7, 191-200
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    Mitochondrial toxicity of organic arsenicals: membrane permeability transition pore opening and respiratory dysfunction

    X. Fan, L. Yuan, C. Wu, Y. Liu, F. Jiang, Y. Hu and Y. Liu, Toxicol. Res., 2018, 7, 191
    DOI: 10.1039/C7TX00234C

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