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J Inorg Biochem. 2019 Mar;192:62-71. doi: 10.1016/j.jinorgbio.2018.12.008. Epub 2018 Dec 26.

Trehalose prevents cadmium-induced hepatotoxicity by blocking Nrf2 pathway, restoring autophagy and inhibiting apoptosis.

Author information

1
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China.
2
College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
3
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China. Electronic address: fanruifeng@sdau.edu.cn.
4
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province 271018, China. Electronic address: wanglin2013@sdau.edu.cn.

Abstract

Cadmium (Cd) is a ubiquitously distributed environmental pollutant that is highly toxic to liver. Trehalose (Tr), a novel autophagy activator, has been shown to exert cytoprotective effect in numerous pathological processes. However, it is yet to be established whether Tr affords protection against Cd-induced hepatotoxicity. Here, we aimed to investigate the protective effect of Tr on Cd-induced hepatic injury in rats. First, Cd-elevated serum hepatic enzymes and liver pathological changes were significantly ameliorated by Tr treatment. Also, Tr remarkably improved Cd-mediated oxidative stress and antioxidant status in serum, indicating its anti-oxidant action for the whole body. Cd-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent elevated expression of Nrf2-downstream targets in rat liver were significantly inhibited by Tr treatment. Simultaneously, Cd-elevated protein levels of hepatic antioxidant enzymes were markedly downregulated by administration with Tr. Moreover, Cd-induced autophagy inhibition in liver tissues was noticeably restored by Tr, evidenced by immunohistochemical analysis and immunoblot assays. Additionally, Tr treatment significantly mitigated Cd-induced apoptosis in hepatic tissues via inhibiting caspase-dependent apoptotic pathway. In conclusion, these observations demonstrate that Tr treatment alleviates Cd-induced liver injury by blocking Nrf2 pathway, restoring autophagy and inhibiting apoptosis.

KEYWORDS:

Apoptosis; Autophagy; Cadmium; Liver; Nrf2; Trehalose

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