AUTHOR=Li Na , Liu Feng-Jiao , Li Dan-Dan , Sun Chun-Xia , Li Jian , Qu Mei-Hua , Cui Chun-Ping , Zhang Da-Jin 

TITLE=Hepatopoietin Cn (HPPCn) Generates Protective Effects on Acute Liver Injury

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00646

DOI=10.3389/fphar.2019.00646

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To observe the protective role of hapatopoietin Cn (HPPcn) on acute liver injury.</p><p><bold>Methods:</bold> Six hours after 10 mmol/L CCl<sub>4</sub>, 150 mmol/L ethanol, or 0.6 mmol/L H<sub>2</sub>O<sub>2</sub> treatment, SMMC7721 human hepatoma cells were incubated with 10, 100, or 200 ng/ml recombinant human HPPCn protein (rhHPPCn) for an additional 24 h. The cell survival rate was analyzed using the CCK-8 assay. The CCl<sub>4</sub>-induced apoptosis of SMMC7721 cells was detected by flow cytometry. Then, the levels of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), malondialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) in SMMC7721 cell lysates and cell culture supernatant were detected. SMMC7721 cells were treated with different concentrations of rhHPPCn (0, 10, and 100 ng/ml). The cell proliferation indexes (BrdU incorporation and PCNA expression) were detected by immunohistochemistry (IHC). An acute liver injury mouse model was established by a one-time intraperitoneal injection of 20% CCl<sub>4</sub> at a volume of 5 ml/kg body weight. One hour after CCl<sub>4</sub> injection, 1.25 or 2.5 mg rhHPPCn/12 h/kg body weight was injected <italic>via</italic> the tail vein. The serum levels of GOT and GPT were detected at different time points. Pathological changes in the liver were evaluated. PCNA expression levels were observed by IHC.</p><p><bold>Results:</bold> rhHPPCn increased the survival rate of SMMC7721 cells and inhibited chemical toxicity-induced cell apoptosis. The levels of GOT, GPT, MDA, and LDH in the cell supernatant were significantly reduced, while GSH-PX and SOD were significantly increased after rhHPPCn treatment in the CCl<sub>4</sub>-treated SMMC7721 cells. BrdU incorporation and PCNA expression increased in a concentration-dependent manner, indicating that rhHPPCn promotes cell proliferation. The results showed that rhHPPCn significantly reduced the serum levels of GOT and GPT in CCl<sub>4</sub>-induced acute liver injury mice. rhHPPCn alleviated the tissue damage and increased PCNA expression, indicating the promotion of proliferation after acute injury.</p><p><bold>Conclusion:</bold> rhHPPCn protects hepatocytes from chemical toxins by promoting proliferation and inhibiting apoptosis <italic>in vivo</italic> and <italic>in vitro</italic>. Our study provides new insights for the clinical treatment of acute liver injury.</p>