Aluminum chloride caused liver dysfunction and mitochondrial energy metabolism disorder in rat.

Abstract

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 (AlCl3) treatment rat. To verify the hypothesis, forty male Wistar rats were randomly allocated and orally exposed to 0, 64mg/kg, 128mg/kg and 256mg/kg body weight AlCl3 in drinking water for 120days, respectively. We found that AlCl3 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 AlCl3 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 AlCl3, providing considerable direction for the prevention and clinical intervention of liver diseases.

• Authors: Feibo Xu, Yanfen Liu, Hansong Zhao, Kaiyuan Yu, Miao Song, Yanzhu Zhu, Yanfei Li
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 174 Pg. 55-62 (09 2017) ISSN: 1873-3344 [Electronic] United States
• PMID: 28605655 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• Aluminum Compounds
• Chlorides
• Aluminum Chloride

Topics

• Aluminum Chloride
• Aluminum Compounds (toxicity)
• Animals
• Chemical and Drug Induced Liver Injury (metabolism, pathology)
• Chlorides (toxicity)
• Energy Metabolism (drug effects)
• Liver (metabolism, pathology)
• Male
• Mitochondria, Liver (metabolism, pathology)
• Rats
• Rats, Wistar