Treatment of concanavalin A-induced hepatitis in mice with low molecular weight heparin

Background/Aims: Heparin has been noted to inhibit inflammation independent of its known anti-coagulant activity. In the present study, we examined the ability of heparin and low molecular weight heparin to prevent immune-mediated, concanavalin A-induced liver damage. Methods: Mice were pretreated with either heparin or low molecular weight heparin (Fragmin) prior to their inoculation with concanavalin A (10 mg/kg). Liver enzymes, liver histology, and the serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-10 were examined in the control and treated mice. Results: The histopathologic damage in the liver, and the concanavalin A-induced release of aminotransferases, tumor necrosis factor-α, and interleukin-6 were significantly inhibited in mice pretreated with low molecular weight heparin, whereas the serum levels of the anti- inflammatory cytokine interleukin-10 were increased (p < 0.01). Interestingly, maximal inhibition was obtained with low low molecular weight heparin doses (5 and 1 μg/mouse, p < 0.001), while higher doses were less effective. Concanavalin A-induced liver injury was not prevented by pretreatment of the mice with heparan sulphate (p < 0.001), which although it is structurally similar to heparin possesses neither anti-inflammatory nor anti- coagulant properties. Conclusions: This study demonstrates the efficacy of low molecular weight heparin in preventing immune- mediated liver damage in mice.