Blockade of leukotriene B4 prevents articular incapacitation in rat zymosan-induced arthritis.
We investigated whether leukotrienes mediate cell influx and articular incapacitation in zymosan-induced arthritis. Rats received 1 mg zymosan intra-articularly (i.a.). The hyperalgesia was measured using the rat articular incapacitation test. Cell influx, leukotriene B(4) and prostaglandin E(2) levels were assessed in the joint exudate, at 6 h. Groups received either the leukotriene B(4) synthesis inhibitor MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl)]-2,2-dimethylpropanoic acid 30 min before or 2 h after the zymosan; 0.3-3 mg kg(-1) i.p.), the leukotrienes synthesis inhibitor BWA(4)C (N-(3-phenoxycinnamyl)-acetohydroxamic acid--2 h after the zymosan; 10 microg i.a.) or the peptido-leukotrienes antagonist sodium montelukast (30 min before and 2 h after the zymosan; 10 mg kg(-1) per os). MK 886 inhibited the articular incapacitation and cell influx, while reducing leukotriene B(4), but not prostaglandin E(2) levels. BWA(4)C inhibited the articular incapacitation. Sodium montelukast did not affect either of the parameters. The data suggest that leukotriene B(4) is involved in cell influx and articular incapacitation in zymosan arthritis.
Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Rua Tiburcio Cavalcante, 2100/1201, Dionisio Torres, Fortaleza, Ceará Cep 60125-101, Brazil. arocha@ufc.br
Francisco Airton Castro
FA
da Rocha
Mauro Martins
MM
Teixeira
José Carlos da Silva
JC
Rocha
Virgínia Cláudia Carneiro
VC
Girão
Mirna Marques
MM
Bezerra
Ronaldo de Albuquerque
Rde A
Ribeiro
Fernando de Queiroz
Fde Q
Cunha
D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D044482:Benzeneacetamides / Q000494:pharmacology / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D003521:Cyclopropanes; D005122:Exudates and Transudates / Q000166:cytology; D006614:Hindlimb; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D008297:Male; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides; D015054:Zymosan; D002722:Chlorobenzenes
D000085:Acetates; D044482:Benzeneacetamides; D003521:Cyclopropanes; D006877:Hydroxamic Acids; D007211:Indoles; D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D011804:Quinolines; D013440:Sulfides; D015054:Zymosan; C060893:MK-886; D002722:Chlorobenzenes; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; C093875:montelukast