Antiinflammatory activities of ph cl28a in rats invivo

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOThe anti-inflammatory effects of Ph CL28A, a potentiator of prostacyclin output and inhibitor of leukotriene (LT) synthesis, were assessed in two models of acute inflammation. In paw oedema induced by carrageenan in rats, Ph CL28A (10-100 mg/kg), given i.p. at the same time as the carrageenan, inhibited oedema for up to 4 h. When indomethacin or Ph CL28A was given locally into the paw with carrageenan, indomethacin inhibited oedema formation but Ph CL28A potentiated the oedema for up to 4 h. As Ph CL28A does not inhibit cyclo-oxygenase, its anti-inflammatory effects in this model may reflect its ability to increase prostacyclin output. In pleurisy induced by carrageenan in rats, there were increases in leukocytes, LTB4, thromboxane B2 (TxB2) and 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha) in the pleural fluid over 3 h. In this model, Ph CL28A (30 mg/kg) given i.p. decreased leukocyte numbers and LTB4 but did not affect TxB2 or 6-oxo-PGF1alpha. Indomethacin decreased both prostanoids but did not affect leukocyte accumulation. The beneficial effects of Ph CL28A in two different models of acute inflammation suggests that it may have potential as an anti-inflammatory agentElsevier2312237242FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçãoAmsterd

Anti-inflammatory Activities Of Ph Cl28a In Rats In Vivo

The anti-inflammatory effects of Ph CL28A, a potentiator of prostacyclin output and inhibitor of leukotriene (LT) synthesis, were assessed in two models of acute inflammation. In paw oedema induced by carrageenan in rats, Ph CL28A (10-100 mg/kg), given i.p. at the same time as the carrageenan, inhibited oedema formation but Ph CL28A potentiated the oedema for up to locally into the paw with carrageenan, indomethacin inhibited oedema formation but Ph CL28A potentiated the oedema for up to 4 h. As Ph CL28A does not inhibit cyclo-oxygenase, its anti-inflammatory effects in this model may reflect its ability to increase prostacyclin output. In pleurisy induced by carrageenan in rats, there were increases in leukocytes, LTB4, thromboxane B2 (TxB2) and 6-oxo-prostaglandin F1α (6-oxo-PGF1α) in pleural fluid over 3 h. In this model, Ph CL28A (30 mg/kg) given i.p. decreased leukocyte numbers and LTB4 but did not affect TxB2 or 6-oxo-PGF1α. Indomethacin decreased both prostanoids but did not affect leukocyte accumulation. The beneficial effects of Ph CL28A in two different models of acute inflammation suggests that it may have potential as an anti-inflammatory agent. © 1983.2312237242Bakhle, Moncada, De Nucci, Salmon, Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung (1985) Br. J. Pharmacol., 86, p. 55Bakhle, Pankhania, Inhibitors of prostaglandin dehydrogenase (Ph CL 28A and Ph CK 61A) increase output of prostaglandins from rat lung (1987) Br. J. Pharmacol., 92, p. 189Berry, Hoult, Phillips, McCarthy, Agback, Highly potent inhibition of prostaglandin 15-hydroxydehydrogenase in vitro and of prostaglandin inactivation in perfused lung by the new azobenzene analogue, Ph CL 28A (1985) J. Pharm. Pharmacol., 37, p. 622Berry, Chastagnol-Hermann, Lloyd, Inhibition of 5-lipoxygenase in vitro by sulphasalazine, Ph CL28A and carbenoxolone (1988) Br. J. Pharmacol., 93, p. 141PBerry, Prouteau, Lloyd, Sulphasalazine and Ph CL28A inhibit the formation of ethanol- and phenylbutazone-induced rat gastric ulcerslack of involvement of endogenous prostaglandins (1988) Br. J. Pharmacol., 93, p. 465Boxer, Allen, Schmidt, Yoder, Baehner, Inhibition of polymorphonuclear leukocyte adherence by prostacyclin (1980) J. Lab. Clin. Med., 95, p. 672Foster, McCormick, Howarth, Aked, Leukocyte recruitment in the subcutaneous sponge implant model of acute inflammation in the rat is not mediated by leukotriene B4 (1986) Biochem. Pharmacol., 35, p. 1709Pankhania, Bakhle, Treatment in vivo with PhCL28A alters prostaglandin E2, prostacyclin and leukotriene C4 metabolism in rat isolated lungs (1990) Pulm. Pharmacol., 3, p. 73Rampart, Williams, Polymorphonuclear leukocyte-dependent plasma leakage in rabbit skin is enhanced or inhibited by prostacyclin depending on the route of administration (1986) Am. J. Pathol., 124, p. 6

Inflammatory responses induced by poly-L-arginine in rat lungs in-vivo

The inflammatory responses induced by the synthetic polycation poly-L-arginine injected either into the pleural cavity or into the trachea in rats have been investigated. Poly-L-arginine (4-40 nmol/rat) injected intrapleurally induced exudate formation and leucocyte migration (mainly polymorphonuclear cells). The exudate formation (but not cell migration) was dependent on the molecular weight of the poly-L-arginine used (24 and 115 kD). The poly-L-arginine-induced pleurisy was mainly dependent on activation of mast cells since it was significantly reduced either in rats depleted of their stores of histamine and serotonin or in rats previously treated with the serotonin receptor antagonist methysergide. The polyanions heparin and dermatan sulphate when administered intrapleurally with the polycation markedly reduced the exudate formation. Poly-L-arginine (115 kD, 8.5 nmol/rat) injected intratracheally caused lung oedema, increased leucocyte number and protein content of bronchoalveolar lavage, respiratory insufficiency and 60% mortality in 6 h. Depletion of histamine and serotonin stores or of circulating neutrophils decreased the leucocytes in bronchoalveolar lavage but did not increase survival rate, whereas the polyanion dermatan sulphate prevented the mortality completely. These results suggest that the inflammatory changes caused by poly-L-arginine are dependent on mast cell activation but that the lethality after intratracheal administration is due to electrostatic interactions of the polycation with anionic surfaces present in the pulmonary epithelium393-410411

Inflammatory Responses Induced By Poly-l-arginine In Rat Lungs In Vivo

The inflammatory responses induced by the synthetic polycation poly-L-arginine injected either into the pleural cavity or into the trachea in rats have been investigated. Poly-L-arginine (4-40 nmol/rat) injected intrapleurally induced exudate formation and leucocyte migration (mainly polymorphonuclear cells). The exudate formation (but not cell migration) was dependent on the molecular weight of the poly-L-arginine used (24 and 115 kD). The poly-L-arginine-induced pleurisy was mainly dependent on activation of mast cells since it was significantly reduced either in rats depleted of their stores of histamine and serotonin or in rats previously treated with the serotonin receptor antagonist methysergide. The polyanions heparin a dermatan sulphate when administered intrapleurally with the polycation markedly reduced the exudate formation. Poly-L-arginine (115 kD, 8.5 nmol/rat) injected intratracheally caused lung oedema, increase leucocyte number and protein content of bronchoalveolar lavage, respiratory insufficiency and 60°, mortality in 6 h. Depletion of histamine and serotonin stores or of circulating neutrophils decreased the leucocytes in bronchoalveolar lavage but did not increase survival rate, whereas the polyanion dermatan sulphate prevented the mortality completely. These results suggest that the inflammatory changes cause by poly-L-arginine are dependent on mast cell activation but that the lethality after intratracheal administration is due to electrostatic interactions of the polycation with anionic surfaces present in the pulmonary epithelium.3903/04/1510411

Race, Medicine, and the Science Behind BiDil: How ACE-Inhibition Took the Fall for the First Ethnic Drug

Heart failure, ACE-inhibition, Racial/ethnic disparities, Statistical analysis, Conflict of interest, BiDil,