Comparison of acute immunological liver injury models in two different species of mice

Abstract

Objective To explore the dose difference on concanavalin A (Con A) induced acute immunological injury of liver in two different species of mice. Methods Thirty six male BALB/C mice and 40 male C57BL/6 mice were randomly divided into 6 groups.BALB/C mice were divided into a control group and five (5, 10, 15, 20 and 25 mg/kg ConA) experimental groups, while C57BL/6 mice were divided into a control group and five (5, 7.5, 10, 12.5 and 15 mg/kg ConA) experimental groups. The experimental groups were injected with different doses of ConA. After 16 hrs of fasting, the serum samples were collected by orbital blood sampling. Biopsy samples of liver,spleen andthymus were weighed and visceral index was calculated. The liver tissue was microscopied with histological technology. The activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was measured by colorimetric method. The release and expression of tumor necrosis factor (TNF-α) were detected using ELISA. Finally, the ConA optimum dose was determined based on animal mortality in each group. Results In BALB/C mice, two animals died at the dosage of 25 mg/kg ConA. The activity of AST, ALT and TNF-α content showed a dose-dependent increase with ConA(P＜0.05). The liver index was positively correlated with the dose of ConA (P＜0.05). The spleen index from group of 5 mg/kg was higher than that from groups of 10 and 15 mg/kg, showing a tend of increase- decrease-increase kinetic profile. In C57BL/6 mice, one animal died at the dosage of 10 mg/kg ConA, one at 12.5 mg/kg and two at 15 mg/kg ConA. The activity of AST,ALT and TNF-α content showed a dose-dependent increase with ConA (P＜0.05). The liver index was positively correlated with the dose of ConA. The spleen index at 7.5 mg/kg was higher than other dose groups, showing a trend of increase followed by decrease. In both strains of mice, thymus index decreased with the increase of dose. The extent of liver lesions in both species of mice was positively correlated with the dose of ConA,progressing from inflammatory cell infiltrates at low doses to liver tissue necrosis at high doses, and from focal necroses to patchy necrotic lesion. Conclusions C57BL/6 mice are more sensitive to ConA than BALB/C mice. The appropriate dosage for BALB/C mice to replicate animal models is 20 mg/kg, while the appropriate dosage for C57BL/6 mice is 10 mg/kg.

Keywords

• concanavalin a|immunological liver injury|mouse model