期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 174, 期 -, 页码 55-62出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2017.04.016
关键词
Aluminum chloride; Liver dysfunction; Mitochondria; Energy metabolism; Oxidative stress
资金
- National Science Foundation [31372496, 31302147]
Aluminum (Al) is known to exert hepatotoxicity. However, the mechanisms mostly are unclear. Liver is a metabolism organ that maintains the energy level and structural stability of body, mitochondria are the main sites of energy metabolism, thus, we hypothesized that mitochondrial energy metabolism disorder contributes to liver dysfunction in aluminum chloride (AICl(3)) treatment rat. To verify the hypothesis, forty male Wistar rats were randomly allocated and orally exposed to 0, 64 mg/kg, 128 mg/kg and 256 mg/kg body weight AICl(3) in drinking water for 120 days, respectively. We found that AICl(3) exposure reduced the electron transport chain complexes I-V activities and adenosine triphosphate (ATP) level, as well as disturbed mitochondrial DNA transcript, presenting as the inhibited mRNA expressions of NADH dehydrogenase 1, NADH dehydrogenase 2, cytochrome b, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3 and ATP synthase 6, indicating that AICl(3) exposure disturbs the mitochondrial energy metabolism, and it caused an increase in liver enzymes (Aspartate aminotransferase and Alanine aminotransferase) and histopathological lesions. Additionally, we found that reactive oxygen species accumulation and decreased superoxide dismutase activity in mitochondria, and increased 8-Hydroxydeoxyguanosine levels in mitochondrial DNA, demonstrating AlCl3 exposure promotes mitochondrial oxidative stress, which may be a contributing factor to mitochondrial energy metabolism disorder and liver dysfunction. The study displayed that mitochondria are the potential target of liver damage induced by AICl(3), providing considerable direction for the prevention and clinical intervention of liver diseases.
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