Protecting Effect Of JBP485 On Concanavalin A-induced Liver Injury In Mice

Background: Cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) was first isolated from Laennec, a trade name for the hydrolysate of human placenta. The aim of this study was to examine the effect of JBP485 on immune-mediated, concanavalin A (Con A)-induced liver injury in mice.Methods: BALB/c female mice were administered JBP485 with kinds of doses (3.125mg/kg,12.5mg/kg,25mg/kg,50mg/kg) before and after injection of Con A (10 mg/kg, 1.5mg/ml) from tail vein. 8 h after Con A, the cytosolic enzyme activities (alanine aminotransferase, lactate dehydrogenase) in serum were determined with and without JBP485. To illuminate the protecting mechanisms of JBP485, we determined, the enzyme activities or concentration of superoxide dismutase(SOD), maleic dialdehyde(MDA), myeloperoxidase(MPO), nitric oxide(NO) in liver homogenate and in liver slices after administration of JBP485 in Con A-induced liver injury in mice. The effects of JBP485 on levels of tumor necrosis factor-α(TNF-α) and cell-adhesion molecules (intracellular adhesion molecule-1 [ICAM-1]) in liver were also detected by immunohistochemistry. Hepatocyte DNA fragmentation was assayed by agarose gel electrophoresis, and the transcription of the genes bax and bcl-2 in hepatocytes was determined by reverse transcription-polymerase chain reaction.Results: The increases in cytosolic enzyme activities, and increases in the concentrations of ICAM-1 and TNF-αwere inhibited significantly by JBP485 administration in Con A-induced liver injury in mice. The increases in DNA fragmentation, which was induced by Con A administration, was significantly inhibited by JBP485. The bcl-2 and the ratio of bcl-2/bax mRNA level which determines whether or not apoptosis can occur, were significantly decreased when exposed to Con A, but was increased following JBP485 administrationConclusion: This study demonstrates that immune-mediated liver damage in mice can be prevented by JBP485, which is mainly associated with immunomodulatory effects on inflammatory cells and adhesion molecules, antioxidation, and inhibition of apoptosis.