Phycocyanobilin accelerates liver regeneration and reduces mortality rate in carbon tetrachloride-induced liver injury mice

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.