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Rat Liver Mitochondrial Dysfunction Induced by an Organic Arsenical Compound 4-(2-Nitrobenzaliminyl) Phenyl Arsenoxide

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Abstract

Arsenic is successfully used in cancer chemotherapy and several cancer treatments on account of its apoptogenic effects. However, it is environmentally hazardous with potential for toxicity when distributed in the soil, water, and food, and long exposure to water contaminated with Arsenic may induce cancers. Some research studies have reported that liver is the storage site and an important target organ for Arsenic toxicity. In the present work, a new kind of organic arsenic compound, 4-(2-nitrobenzaliminyl) phenyl arsenoxide (NPA), was synthesized, and its potential involvement of mitochondria was explored. The results presented that the toxicology of NPA, at least in part, mediated mitochondrial function and may thoroughly destroy mitochondrial membrane physiological functions. NPA induced mitochondrial permeability transition pore (mtPTP) opening that induces mitochondrial biochemical abnormalities as evidenced by mitochondrial swelling, mitochondrial membrane potential breakdown, membrane fluidity alterations, and the strikingly remarkable protection of CsA. Meanwhile, both the decreased respiration rate of state 4 and the increased inner membrane H+ permeabilization revealed that the inner membrane function regarding important energy production chain was destroyed. The toxicity of NPA is due to its interaction with mitochondrial membrane thiol protein. This conclusion is based on the protective effects of RR, DTT, and MBM+.

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Acknowledgments

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (No. 21225313); Hubei Natural Science Foundation of China (No. 3013CFC027); B Plan of Hubei Provincial Education Office of China (No. B20114404) and the Hubei Polytechnic University Program of China (No.14xjz03A).

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Authors and Affiliations

  1. State Key Laboratory of Viology and Key Laboratory of Ananlytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, People’s Republic of China

    Yuan-Hong Jiao, Xin-You Chen, Jie Zhao, Feng-Lei Jiang & Yi Liu

  2. College of Chemistry and Chemical Engineering, Hubei Polytechnic University, Huangshi, 435003, People’s Republic of China

    Yuan-Hong Jiao & Qian Zhang

  3. Center Hospital of Huangshi City, Huangshi, 435002, Hubei, People’s Republic of China

    Ling-Li Pan

  4. School of Chemical Engineering and Food Science, Hubei University of Arts and Science, Xiangyang, 441053, People’s Republic of China

    Ke-Lin Lei

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  1. Yuan-Hong Jiao
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  2. Qian Zhang
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  4. Xin-You Chen
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Correspondence to Jie Zhao.

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Jiao, YH., Zhang, Q., Pan, LL. et al. Rat Liver Mitochondrial Dysfunction Induced by an Organic Arsenical Compound 4-(2-Nitrobenzaliminyl) Phenyl Arsenoxide. J Membrane Biol 248, 1071–1078 (2015). https://doi.org/10.1007/s00232-015-9818-5

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  • DOI: https://doi.org/10.1007/s00232-015-9818-5

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