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Food Chem Toxicol. 2019 Jan;123:536-545. doi: 10.1016/j.fct.2018.12.012. Epub 2018 Dec 10.

Pterostilbene protects against acetaminophen-induced liver injury by restoring impaired autophagic flux.

Author information

1
School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
2
School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea. Electronic address: allzzangjk@naver.com.
3
School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea. Electronic address: sunmee@skku.edu.

Abstract

An overdose of acetaminophen (APAP) causes liver injury through formation of N-acetyl-p-benzoquinoneimine, which overproduces reactive oxygen species (ROS). Autophagy maintains cellular homeostasis and is regulated by generation of ROS. Pterostilbene (PTE) has been shown to have antioxidant and anti-inflammatory properties. In this study, we investigated the protective mechanisms of PTE against APAP-induced liver injury, focusing on autophagy. ICR mice were intraperitoneally (i.p.) treated with 400 mg/kg of APAP. PTE (15, 30, and 60 mg/kg, i.p.) and chloroquine (CQ, 60 mg/kg, i.p.) were injected 1 h after APAP treatment. Blood and liver tissues were isolated 6 h after APAP treatment. PTE decreased serum aminotransferase activities and hepatic oxidative stress; this protective effect was abolished by CQ. APAP impaired autophagic flux, as evidenced by increased microtubule-associated protein-1 light chain 3-II and p62 protein expression; this impaired autophagic flux was restored by PTE, while CQ abolished this effect. APAP decreased beclin-1 and autophagy related protein 7 protein expressions, while PTE attenuated these decreases. PTE increased the lysosome-associated membrane protein-2 protein expression and decreased the mammalian target of rapamycin and Unc-51 like autophagy activating kinase 1 phosphorylation. Our findings suggest that PTE protects against APAP-induced hepatotoxicity by enhancing autophagic flux.

KEYWORDS:

Acetaminophen; Autophagic flux; Hepatotoxicity; Oxidative stress; Pterostilbene

PMID:
30543896
DOI:
10.1016/j.fct.2018.12.012
[Indexed for MEDLINE]

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