Research Paper Volume 14, Issue 17 pp 6993—7002
Phellinus linteus polysaccharides mediates acetaminophen-induced hepatotoxicity via activating AMPK/Nrf2 signaling pathways
- 1 Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, P.R. China
- 2 Reproductive Medical Center, The Second Hospital of Jilin University, Changchun 130041, Jilin, P.R. China
Received: May 25, 2022 Accepted: August 25, 2022 Published: September 1, 2022https://doi.org/10.18632/aging.204260
How to Cite
Copyright: © 2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Overdose of acetaminophen (APAP) is currently one of the main causes of hepatoxicity and acute liver injury, which is often linked to oxidative stress. Phellinus linteus polysaccharides (Phps) have shown many hepatoprotective effects, however, the mechanism of Phps on APAP-induced acute liver injury has not been further elucidated. The aim of this study is to investigate the underlying mechanism of Phps to acute liver injury. The expression of AMPK/Nrf2 and autophagy were detected using western blot. The results indicated that Phps treatment effectively alleviated APAP-induced acute liver injury by reducing alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum. Phps significantly attenuated myeloperoxidase (MPO) activity and glutathione (GSH) depletion. Meanwhile, Phps remarkably alleviated histopathological changes. Further research found that Phps promoted AMPK pathway and up-regulated nuclear factor erythroid-2-related factor (Nrf2) transported into nucleus, and elevated heme oxygenase 1(HO-1), glutamate-cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM) and quinone oxidoreductase (NQO1). Additionally, Phps apparently facilitated the expression of autophagy proteins (ATG3, ATG5, ATG7, and ATG12). However, the protection of pathologic changes was nearly absent in Nrf2-/- mice. Phps have potential in preventing oxidative stress in APAP-induced acute liver injury.
APAP: Acetaminophen; Phps: Phellinus linteus polysaccharides; ALT: Alanine transaminase; AST: Aspartate aminotransferase; MPO: Myeloperoxidase; GSH: Glutathione; Nrf2: Nuclear factor erythroid-2-reated factor; HO-1: Heme oxygenase 1; GCLC: Glutamate-cysteine ligase catalytic; GCLM: Glutamate cysteine ligase modifier; NQO1: Quinone oxidoreductase; AMPK: Adenosine5’-monophosphate (AMP)-activated protein kinase.