Investigation of the effect of unfractionated and low molecular weight heparins on inflammation and gastrointestinal mucosal injury in rats

ABSTRACT

The aim of the present work was to investigate the effect of unfractionated heparin [UFH; 1000-4000 IU/kg] in addition to three already marketed low molecular weight heparin [LMWH] preparations [nadroparin [1500-3000 anti-Xa IU/kg], tinzaparin [1500-3000 anti-Xa IU/kg], enoxaparin [300-600 anti-Xa IU/kg] on acute inflammation and on gastrointestinal mucosal integrity in rats. Acute inflammation was induced by intraplantar injection of carrageenan into rat hindpaw. Gastrointestinal mucosal injury was evoked by subcutaneous injection of indomethacin [20 mg/kg]. The results showed that [1] Different heparin preparations given s.c., 30 mm prior to carrageenan injection exerted variable effects on the carrageenan oedema response. Oedema was not significantly changed after conventional UFH, but decreased after tinzaparin and nadroparin, the lower doses being more effective in reducing inflammation. Oedema was unchanged after enoxaparin at 600 IU/kg, but the lower dose of 300 IU/kg reduced oedema formation by 21.6% 1 h post-carrageenan.; [2] No significant change was noted in the number and severity of gastric mucosal lesions in rats treated with UFH. A significant decrease in number and severity of gastric mucosal lesions was noted in rats treated with the lower doses of either tinzaparin or enoxaparin compared with either the indomethacin control group or with the UFH [2000 IU/kg]-treated group. It is concluded that heparin preparations exert complex effects on acute [carrageenan-induced] inflammation and might have beneficial effects on gastric mucosal lesions caused by Indomethacin