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Front. Physiol. | doi: 10.3389/fphys.2019.00660

Tempol protects against acetaminophen induced acute hepatotoxicity by inhibiting oxidative stress and apoptosis

 Junhong Hu1*, Zheng Ge1, Chenyu Wang1, Junjie Zhang1 and Xingwang Li1
  • 1Henan University Huaihe Hospital, China

Acetaminophen (APAP) induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with a single dose of tempol (20 mg/kg per day) orally for 7 days. On the seventh day, mice were injected with a single dose of APAP (300 mg/kg) to induce acute hepatotoxicity. Our results showed that tempol treatment markedly improved liver functions with alleviations of histopathological damage induced by APAP. Tempol treatment upregulated levels of antioxidant proteins, including superoxide dismutase, catalase and glutathione. Also, phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) and protein expression of Nuclear factor erythroid 2-related factor (Nrf 2) and heme oxygense-1 (HO-1) were all increased by tempol, which indicated tempol protected against APAP-induced hepatotoxicity via the PI3K/Akt/Nrf2 pathway. Moreover, tempol treatment decreased pro-apoptotic protein expressions (cleaved caspase-3 and Bax) and increased anti-apoptotic Bcl-2 in liver, as well as reducing apoptotic cells of TUNEL staining, which suggested apoptotic effects of tempol treatment. Overall, we found that tempol normalizes liver function in APAP-induced acute hepatotoxicity mice via activating PI3K/Akt/Nrf2 pathway, thus enhancing antioxidant response and inhibiting hepatic apoptosis.

Keywords: Acetaminophen, Acute hepatotoxicity, Tempol, Oxidative Stress, Apoptosis

Received: 01 Mar 2019; Accepted: 09 May 2019.

Edited by:

Honglei Weng, Universität Heidelberg, Germany

Reviewed by:

Isabel Fabregat, Biomedical Research Institute of Bellvitge, Spain
Matthias J. Bahr, Sana Kliniken Lübeck, Germany  

Copyright: © 2019 Hu, Ge, Wang, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Junhong Hu, Henan University Huaihe Hospital, Kaifeng, China, hjh-8282@163.com