Effect of licofelone against NSAIDs-induced gastrointestinal ulceration and inflammation.
The present study was aimed to evaluate the effect of licofelone, a dual inhibitor of cycloxygenase1/2-5-lipoxygenase against indomethacin-induced gastric damage in rats and mice in order to assess the role of leukotrienes if any, in non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal inflammation. Acute pretreatment with licofelone reversed the indomethacin-induced gastric ulceration, neutrophil adhesion in mesentery venules, neutrophil count in blood, lipid peroxides and vascularity in the stomachs of mice and rats. Further, chronic pretreatment of licofelone also prevented indomethacin-induced gastric morphological changes and cellular infiltration in mesentery venules. Moreover, acute administration of indomethacin elevated leukotriene B4 levels in gastric mucosa, which was reversed by pretreatment with licofelone The results suggest that licofelone offered gastroprotection against NSAIDs-induced gastropathy through its effect on leukotrienes and by inhibiting extravasation of neutrophils.
Singh
Vijay Pal
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014.
Patil
Chandrashekhar S
CS
Kulkarni
Shrinivas K
SK
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy*; D007975:Leukotriene B4 / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008643:Mesentery / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy*; D013997:Time Factors
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D011758:Pyrroles; D007975:Leukotriene B4; C088092:licofelone; D007213:Indomethacin