Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2015; 21(26): 8089-8095
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8089
Liuweiwuling tablets attenuate acetaminophen-induced acute liver injury and promote liver regeneration in mice
Yan-Chang Lei, Wen Li, Pan Luo
Yan-Chang Lei, Department of Infectious Diseases, Zhejiang Hospital, Hangzhou 310013, Zhejiang Province, China
Wen Li, Pan Luo, Infectious Diseases Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Author contributions: Lei YC designed this research; Lei YC, Li W and Luo P performed this research and analyzed the data; and Lei YC wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Zhejiang Hospital Institutional Review Board.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yan-Chang Lei, Chief Physician, Department of Infectious Diseases, Zhejiang Hospital, No. 12 Lingyin Road, Hangzhou 310013, Zhejiang Province, China. ycleihust@sina.com
Telephone: +86-571-81595081 Fax: +86-571-87980175
Received: November 30, 2014
Peer-review started: November 30, 2014
First decision: January 8, 2015
Revised: February 4, 2015
Accepted: March 30, 2015
Article in press: March 31, 2015
Published online: July 14, 2015
Processing time: 225 Days and 16.7 Hours
Abstract

AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.

METHODS: Intraperitoneal injections of acetaminophen (250 mg/kg) were used to induce acute liver injury in male C57BL/6 mice. A total of 24 healthy mice were randomly assigned to two groups: an acute liver injury group (control group) and a Liuweiwuling tablet group. Mice were given Liuweiwuling tablets or a vehicle (PBS) orally prior to the administration of acetaminophen. Serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) levels were measured at different time points within one week, and pathological examinations of liver tissues were performed 36 h after induction of acute liver injury. Serum inflammatory cytokines, such as high mobility group box protein B1 (HMGB1), tumor necrosis factor (TNF)-α and interleukin IL-1β, were detected using an ELISA method according to the manufacturer’s instructions. Hepatic morphological changes at 36 h were assessed by hematoxylin and eosin staining. Expression of proliferating cell nuclear antigen (PCNA) in liver tissue was determined by Western blot analysis. The mRNA levels of hepatocyte proliferation markers (PCNA, CyclinD1 and p21) were detected by real-time quantitative reverse transcription-polymerase chain reaction.

RESULTS: The levels of ALT/AST in the Liuweiwuling tablet group were decreased significantly at 6, 12 and 24 h compared to that of the control group (654.38 ± 120.87 vs 1566.17 ± 421.64, 1154.18 ± 477.72 vs 4654.84 ± 913.71 and 935.13 ± 252.34 vs 4553.75 ± 727.37, P < 0.01). Serum HMGB1 levels at 6 and 12 h for the Liuweiwuling tablet group were significantly lower than those of the control group (23.49 ± 3.89 vs 58.6 ± 3.65, 61.62 ± 13.07 vs 27.32 ± 5.97, P < 0.01). Furthermore, serum TNF-α and IL-1β levels at 12 h in the Liuweiwuling tablet group were also significantly lower than those of the control group (299.35 ± 50.61 vs 439.03 ± 63.59, 57.42 ± 12.98 vs 160.07 ± 49.87, P < 0.01). Centrilobular necrosis was evident in liver tissue of mice with acetaminophen-induced acute liver injury, but was almost abolished in the Liuweiwuling tablet group. The expression levels of PCNA and CyclinD1 were up-regulated in liver tissue in the Liuweiwuling tablet group (321.08 ± 32.87 vs 157.91 ± 21.52, 196.37 ± 25.39 vs 68.72 ± 11.27, P < 0.01); however, expression of p21 in liver tissue was down-regulated compared to that of the control group (40.26 ± 9.97 vs 138.24 ± 13.66, P < 0.01).

CONCLUSION: Liuweiwuling tablets can attenuate acute liver injury by decreasing inflammatory cytokine (HMGB1, TNF-α and IL-1β) levels and promoting liver regeneration.

Keywords: Acute liver injury; Acetaminophen; Liuweiwuling tablets; Inflammatory cytokine; Liver regeneration

Core tip: Clinical studies have shown that Liuweiwuling tablets are effective against a variety of liver injuries; however, its mechanism has not been established, especially for drug-induced liver injury. In this study, we found that Liuweiwuling tablets can attenuate acetaminophen-induced acute liver injury by decreasing inflammatory cytokine levels and promoting liver regeneration. Our results provide direct evidence for the effective therapy of liver damage with Liuweiwuling tablets and their value in clinical applications. Moreover, this is the first report showing that Liuweiwuling tablets can promote liver regeneration.