Dual role of cadmium in rat liver: Inducing liver injury and inhibiting the progression of early liver cancer.

Autor: Zhang H; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Yan J; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, 730000, Gansu, People's Republic of China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Medical College Cancer Center of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Xie Y; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Chang X; Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Li J; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, 730000, Gansu, People's Republic of China., Ren C; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Zhu J; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Department of Pathology, Donggang District, First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Ren L; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Medical College Cancer Center of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Qi K; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, 730000, Gansu, People's Republic of China., Bai Z; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, 730000, Gansu, People's Republic of China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Medical College Cancer Center of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China., Li X; The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, 730000, Gansu, People's Republic of China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Medical College Cancer Center of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China. Electronic address: lxdr21@126.com.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2022 Feb 01; Vol. 355, pp. 62-81. Date of Electronic Publication: 2021 Nov 14.
DOI: 10.1016/j.toxlet.2021.11.004
Abstrakt: The heavy metal cadmium (Cd) can induce damage in liver and liver cancer cells; however, the mechanism underlying its toxicity needs to be further verified in vivo. We daily administered CdCl 2 to adult male rats at different dosages via gavage for 12 weeks and established rat liver injury model and liver cancer model to study the dual role of Cd in rat liver. Increased exposure to Cd resulted in abnormal liver function indicators, pathological degeneration, rat liver cell necrosis, and proliferation of collagen fibres. Using immunohistochemistry, we found that the area of GST-P-positive precancerous liver lesions decreased in a dose-dependent manner. Real-time quantitative polymerase chain reaction, western blot, immunohistochemistry, and transmission electron microscopy revealed that Cd induced mitophagy, as well as mitophagy blockade, as evidenced by the downregulation of TOMM20 and upregulation of LC3II and P62 with increasing Cd dose. Next, the expression of PINK1/Parkin, a classic signalling pathway protein that regulates mitophagy, was examined. Cd was found to promote PINK1/Parkin expression, which was proportional to the Cd dose. In conclusion, Cd activates PINK1/Parkin-mediated mitophagy in a dose-dependent manner. Mitophagy blockade likely aggravates Cd toxicity, leading to the dual role of inducing liver injury and inhibiting the progression of early liver cancer.
Competing Interests: Declaration of Competing Interest The authors report no declarations of interest.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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