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Mitochondrial oxidative stress-induced hepatocyte apoptosis reflects increased molybdenum intake in caprine

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Abstract

Molybdenum (Mo) is an essential trace element for animals and humans. However, the high dietary intake of Mo leads to disease conditions in heavy metal pollution areas. To the best of our knowledge, the effect of high levels of Mo on the apoptosis of hepatocyte in goats has not been investigated. Therefore, the aim of the present in vivo study was to investigate the impact of Mo on mitochondrial oxidative stress and apoptosis genes in the liver using real-time quantitative polymerase chain reaction (RT-qPCR) and transmission electron microscopy, respectively. Thirty-six healthy goats were randomly divided into three groups: two groups treated with ammonium molybdate [(NH4)6·Mo7O24·H2O] at 15 and 45 mg Mo kg−1 BW, respectively, and a control group without treatment. Liver samples were collected from individual goats at different time intervals. The levels of oxidative stress in the mitochondrial membrane and expression of liver-related apoptosis genes, including Bcl-2, Cyt c, caspase-3, and Smac, were examined. The results demonstrated that the levels of superoxide dismutase (SOD) and catalase (CAT) expression were significantly down-regulated in liver cells, whereas malondialdehyde (MDA), nitric oxide (NO), and total nitric oxide synthase (T-NOS) expression was up-regulated (P < 0.01). The expression of Smac, Cyt c, and caspase-3 was significantly up-regulated, whereas Bcl-2 expression was down-regulated in liver cells (P < 0.01). In addition, histopathological examination revealed varying degrees of vacuolization, irregularity, nuclear fission, and mitochondrial swelling and high-density electrons in the cytoplasm of hepatocytes in groups treated with 15 and 45 mg Mo kg−1 BW. Thus, these results suggested that high molybdenum induced hepatocyte apoptosis and might involve a mitochondrial pathway.

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Acknowledgments

The research was financially supported through grants from the Program of the National Nature Science Foundation (no. 31101863, Beijing, People’s Republic of China), the Training Plan for Young Scientists of Jiangxi province (no. 2014BCB23040, Nanchang, People’s Republic of China), and the Educational Departmental Science Foundation of Jiangxi province (No.GJJ14294, Nanchang, People’s Republic of China) to Huabin Cao.

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The authors declare that there are no conflicts of interests.

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Correspondence to Guoliang Hu or Huabin Cao.

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Yu Zhuang and Ping Liu contributed equally to this work.

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Zhuang, Y., Liu, P., Wang, L. et al. Mitochondrial oxidative stress-induced hepatocyte apoptosis reflects increased molybdenum intake in caprine. Biol Trace Elem Res 170, 106–114 (2016). https://doi.org/10.1007/s12011-015-0450-0

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  • DOI: https://doi.org/10.1007/s12011-015-0450-0

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