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

Abstract：

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-a, 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-a, 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 microg/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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Hershkoviz R,Bruck R,Aeed H,Shirin H,Halpern Z

doi

10.1016/s0168-8278(99)80284-0

subject

Has Abstract

pub_date

1999-11-01 00:00:00

pages

834-40

issue

5

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(99)80284-0

journal_volume

31

pub_type

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