Pentadecapeptide BPC 157 efficiently reduces radiation-induced liver injury and lipid accumulation through Kruppel-like factor 4 upregulation both in vivo and in vitro.

AIMS:Radiation-induced liver disease (RILD) is the major complication for cancer patients after radiation therapy. We investigated the protective effects of BPC 157 peptide in reducing RILD. MATERIALS AND METHODS:Mice were irradiated with a single dose of 12 Gy to induce acute liver injury with or without oral BPC 157. Plasma levels of AST and ALT were determined. In vitro rat liver clone 9 cells and in vivo liver tissues were harvested for MTT assay, TUNEL assay, lipid staining, polypoid cell counts, Western blotting of caspase-3, PCNA, KLF-4 and HIF-2α, and immunocytochemistry for PCNA, KLF-4 and HIF-2α. SiRNAs were used to knockdown KLF-4. KEY FINDINGS:BPC 157 was firstly demonstrated to reduce RILD by decreasing plasma levels of AST and ALT, and inhibiting hydropic degeneration of liver. BPC 157 significantly decreased radiation-induced cell apoptosis, increased PCNA expression, promoted the expression of KLF4, decreased the radiation-induced hepatic lipid accumulation and HIF-2α expression both in mice liver and in clone 9 liver cells. The knockdown of KLF4 abolished the protective effect of BPC 157 on radiation-induced apoptosis and lipid accumulation in clone 9 liver cells, indicating that the protective effect of BPC 157 was mediated by KLF4 in liver cells. SIGNIFICANCE:The present study provided a good model for molecular mechanism underlying the acute RILD. BPC 157, as a stable pentadecapeptide that can be chemically synthesized and purified easily for research, together with its in vivo markedly protective effect made it worth of being investigated for future clinical application for RILD.