Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5465-5472
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5465
Phycocyanobilin accelerates liver regeneration and reduces mortality rate in carbon tetrachloride-induced liver injury mice
Jie Liu, Qing-Yu Zhang, Li-Ming Yu, Bin Liu, Ming-Yi Li, Run-Zhi Zhu
Jie Liu, Qing-Yu Zhang, Bin Liu, Ming-Yi Li, Run-Zhi Zhu, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China
Li-Ming Yu, Department of Maxillofacial Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China
Author contributions: Liu J and Zhang QY contributed equally to this work; Liu J and Zhang QY performed the majority of experiments; Liu B and Yu LM participated in the sample collection of mice; Zhu RZ designed the experiments and guided their implementation; and Li MY provided the funding for supporting this research.
Supported by Zhanjiang Key Laboratory of Hepatobiliary Diseases, No. 2013A402-4; The Medical Research Funding of Affiliated Hospital of Guangdong Medical College, No. QK1319; and The Medical Research Funding of Guangdong Province, No. B2014306, China.
Ethics approval: The protocol of this study was approved by the Committee on the Ethics of Animal Experiments of Guangdong Medical College (Permit Number: SYXK 2008-0007).
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Guangdong Medical College (IACUC protocol number: AP3324).
Conflict-of-interest: Zhu RZ has received research funding from Guangdong Medical College, Li MY has received research funding from Zhanjiang Science and Technology Bureau; Liu J has received research funding from public health and family planning council of Guangdong Province and Affiliated Hospital of Guangdong Medical College respectively; Liu J, Zhang QY, Yu LM, Liu B, Li MY and Zhu R are employees of Affiliated Hospital of Guangdong Medical College; all authors declare that there is no conflict of interest in this work.
Data sharing: 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: Run-Zhi Zhu, PhD, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, South NO. 57 Renmin Dadao, Zhanjiang 524001, Guangdong Province, China. hepatolab@163.com
Telephone: +86-759-2387596 Fax: +86-759-2387596
Received: November 7, 2014
Peer-review started: November 10, 2014
First decision: December 11, 2014
Revised: December 29, 2014
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: May 14, 2015
Abstract

AIM: To investigate the hepatoprotective effects of phycocyanobilin (PCB) in reducing hepatic injury and accelerating hepatocyte proliferation following carbon tetrachloride (CCl4) treatment.

METHODS: C57BL/6 mice were orally administered PCB 100 mg/kg for 4 d after CCl4 injection, and then the serum and liver tissue of the mice were collected at days 1, 2, 3, 5 and 7 after CCl4 treatment. A series of evaluations were performed to identify the curative effects on liver injury and recovery. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and superoxide dismutase (SOD) were detected to indirectly assess the anti-inflammatory effects of PCB. Meanwhile, we detected the expressions of hepatocyte growth factor, transforming growth factor alpha (TGF-α), TGF-β, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), the factors which are associated with inflammation and liver regeneration. The protein expressions of proliferating cell nuclear antigen (PCNA), TNF-α and cytochrome C were detected by western blot. Furthermore, the survival rates were analyzed of mice which were administered a lethal dose of CCl4 (2.6 mg/kg) with or without PCB.

RESULTS: In our research, PCB showed a strongly anti-inflammatory effect on CCl4-induced liver injury in mice. The ALT was significantly decreased after CCl4 treatment from day 1 (P < 0.01) and the AST was significantly decreased from day 2 (P < 0.001). Both albumin and liver SOD were increased from day 2 (P < 0.001 and P < 0.01), but serum SOD levels did not show a significant increase (P > 0.05). PCB protected the structure of liver from the injury by CCl4. TUNEL assay showed that PCB dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control (101.0 ± 25.4 vs 25.7 ± 6.4, P < 0.01). The result of western blotting showed that PCB could increase PCNA expression, decrease TNF-α and cytochrome C expression. Furthermore, data shows that PCB could improve the survival rate of acute liver failure (ALF) mice which were injected with a lethal dose of CCl4 (60.0% vs 20.0%).

CONCLUSION: Our study indicated that PCB could be an ideal candidate for reversing acute liver injury or ALF.

Keywords: Liver injury, Hepatoprotective, Tumor necrosis factor-alpha, Phycocyanobilin, Cytochrome C

Core tip: Our research confirmed that phycocyanobilin (PCB) plays a hepatoprotective role on carbon tetrachloride-induced acute liver injury mice. It was shown that PCB has a strongly anti-inflammatory effect when the liver suffered oxidative damage. The results showed that PCB could accelerate liver regeneration, reduce apoptosis and necrosis of the hepatocytes by regulating the expression of hepatocyte growth factor, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor-α and interleukin-6. In addition, PCB could significantly improve the survival probability of the acute liver injury mice.