Study On Salecan In Immunology Of Protect Liver Injury In Mice And Antitumor Functioning

Salecan is a recently identified water-soluble viscous extracellular β-1,3-glucan. It has been reported to possess a variety of biological activities. Here we used C57BL/6 mice to get an acute liver injury model to investigate the protection against liver damage by Salecan. We also used C57BL/6 mice to get a pulmonary metastasis model to investigate the antitumor effect of Salecan.For preparation of mice with D-galactosamine(D-GalN)/Lipopolysaccharide(LPS)-induced acute liver injury, C57BL/6 mice were given an intraperitoneal injection of D-GalN (500 mg/kg body weight) and LPS (5 μg/kg body weight) in phosphate-buffered saline (PBS). The D-GalN/LPS-treated mice began to die at 6 h after D-GalN/LPS treatment and survival rate was 0% at 24h, whereas survival rate in Salecan+D-GalN/LPS treated mice was 100% at 24 h. Injection with Salecan significantly reduced activities of serum alanine transaminase (ALT) and aspartate transaminase (AST). Histopathological examination showed that Salecan mitigated hepatic necrosis and pathological changes of liver cells. Salecan pretreatment significantly reduced the serum levels of tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β), interleukin-6 (IL-6) and hepatic mRNA expressions of TNF-a, IL-6, IL-1β. Moreover, Salecan significantly reduced the mRNA levels of TNF-a, IL-6, IL-1β and iNOS in LPS-treated murine macrophages in a dose dependent manner. Research showed that Salecan significantly decreased the levels of phospho-JNK and phospho-ERK in mitogen-activated protein kinase (MAPK) pathway and attenuated LPS-induced NF-kB nuclear translocation. We speculated that Salecan might impact the expression of the downstream gene via inhibiting JNK, ERK and NF-kB activation. The results showed that Salecan highly protected against D-GalN/LPS-induced liver injury.B16F10 melanoma cells were injected into the tail vein of mice and Salecan was administered at doses of 5 mg/kg or 20 mg/kg alternate days. In murine pulmonary metastasis model of B16F10 melanoma, Salecan treatment significantly inhibited lung metastasis in a dose dependent manner. Salecan elevated the spleen index but could not increase the thymus index. Salecan significantly increased the mRNA levels of TNFa, IL-1β, and IL-6 in murine spleen. Cytotoxicity assay revealed that Salecan is non-toxic to B16F10 cells at a dose of 0 to 100 μg/mL. Salecan treatment induced both mRNA expression and protein secretion of the inflammatory cytokines TNFa and IL-1β in RAW264.7 cells in a time dependent manner. The results indicated that Salecan markedly inhibited melanoma cell metastasis in mice, and Salecan exerted its antitumor activity via immune activation of splenocytes and macrophages.