Anti-inflammatory effects of low molecular weight heparin derivative in a rat model of carrageenan-induced pleurisy.

摘要: Low molecular weight heparin derivatives are characterized by low anti-coagulant activity and marked anti-inflammatory effects that allow for these molecules to be viewed as a new class of non-steroidal drugs (NSAIDs). We show here K5NOSepiLMW, an O-sulphated heparin-like semi-synthetic polymer the D-glucuronic acid-N-acetyleparoson disaccharide unit with weight, has in rat model acute inflammation, carrageenan-induced pleurisy, commonly used test NSAID efficacy. A 30-min. pre-treatment K5NOSepiLMW (0.1, 0.5 1 mg/kg b.wt., given intrapleurally) attenuated recruitment leucocytes lung tissue pleural exudate, inhibited induction inducible nitric oxide synthase cyclooxygenase-2 (COX-2), thereby abating generation pro-inflammatory prostaglandins such PgE(2) PGF(1alpha), reduced inflammation-induced nitroxidative injury, shown thiobarbituric acid-reactive substances nitrotyrosine, blunted local cytokines interleukin-1beta tumour necrosis factor-alpha. All parameters were markedly increased intrapleural carrageenan absence any pre-treatment. The action is specific, judged lack therapeutic B4/110, biologically inactive cognate polysaccharide, place authentic molecule. Moreover, showed similar celecoxib (1 b.wt), COX-2 inhibitor well-known NSAID. This study provides further insight into mechanisms underlying beneficial inflammation identifies novel, promising drug.