The Protective Effects of Helix B Surface Peptide on Experimental Acute Liver Injury Induced by Carbon Tetrachloride
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To investigate the protective effects of helix B surface peptide (HBSP) on acute liver injury induced by carbon tetrachloride (CCl4).
HBSP (8 nmol/kg) was intraperitoneally injected into C57 BL/6 mice 2 h after CCl4 administration. Serum and liver tissue samples were collected 24 h after injury. Liver function and histological injuries were evaluated. Inflammatory cell infiltration and cytokines were examined and hepatocytes apoptosis was measured. The human liver cell line LO2 and murine primary hepatocytes were stimulated by CCl4 with and without HBSP treatment and glutathione peroxidase activity, cell survival, and apoptosis were evaluated. In addition, we examined the PI3K/Akt/mTORC1 pathway to elucidate the mechanism underlying HBSP-mediated protection in acute liver injury.
HBSP significantly decreased serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and pro-inflammatory cytokines in liver tissues after CCl4 injection compared with those in the control group. Immunohistochemical staining indicated that the number of CD3-, CD8-, and CD68-positive cells and the expression of cleaved caspase-3 were significantly decreased by HBSP treatment. Additionally, HBSP reduced apoptosis in vivo. In an in vitro study, the glutathione peroxidase activity and survival rate increased, while the total apoptotic rate was reduced in the HBSP-treated group compared with that in the control group after CCl4 treatment. HBSP activated the PI3K/Akt/mTORC1 pathway, which was confirmed by the PI3K inhibitor LY294002 both in vivo and in vitro. Furthermore, HBSP increased the survival of mice with acute liver injury, and this effect was abolished by LY294002.
HBSP is a potential therapeutic agent against acute liver injury induced by CCl4.
KeywordsHelix B surface peptide Acute liver injury Inflammation Apoptosis
Tumor necrosis factor-α
Helix B surface peptide
Methyl thiazolyl tetrazolium
Quantitative real-time polymerase chain reaction
Dulbecco’s modified Eagles medium
Sodium dodecyl sulfate
Analysis of variance
The study was supported by the National Natural Science Foundation of China (Nos. 81301820, 81472673, 81400752, 81401877, 81500457, 81672720), and the National Clinical Key Special Subject of China.
SDW, CY and NX designed the research, conducted the experiments, collected and analyzed the data, and wrote the manuscript. LYW and YL contributed to the data acquisition. JYW and XZS revised the manuscript. All authors reviewed the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval and consent to participate
All animal experiments were performed in accordance with the guidelines of the Care and Use of Laboratory Animals of the Laboratory Animal Ethical Commission of Fudan University with good surgical practices.
Availability of data and materials
The data and all outputs of the current study are available for testing by reviewers and scientists who wish to use them with kind full permission.
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