title: Phycocyanobilin accelerates liver regeneration and reduces mortality rate in carbon tetrachloride-induced liver injury mice.
abstract: OBJECTIVE
  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%).
  
  
  CONCLUSIONS
  Our study indicated that PCB could be an ideal candidate for reversing acute liver injury or ALF.
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Run-Zhi
authors.initials: RZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D009336:Necrosis; D052980:Phycobilins / Q000494:pharmacology*; D010798:Phycocyanin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D052980:Phycobilins; D010798:Phycocyanin; C011069:phycocyanobilin; D002251:Carbon Tetrachloride
keywords: Cytochrome C; Hepatoprotective; Liver injury; Phycocyanobilin; Tumor necrosis factor-alpha