Modulation of polymorphonuclear leukocyte responsiveness by copper (II)2 (niflumate)4.
Antiinflammatory activities and modulations of PMNL responses produced by treatment with tetrakis-mu-2-[3-(trifluoromethyl)-phenyl]aminonicotinatodicopper (II) [Cu(II)2(niflumate)4] and niflumic acid were studied in isologous serum-induced rat pleurisy. Doses of 10 or 30 mg/kg (35 or 106 mumol/kg) of niflumic acid or Cu(II)2(niflumate)4 (8 or 23 mumol/kg) caused significant (p < 0.01) reductions in pleural exudate and number of polymorphonuclear leukocytes (PMNLs) in the exudate. While both doses of Cu(II)2(niflumate)4 produced significant dose-related reductions in both parameters, only the higher dose of niflumic acid produced a significant dose-related reduction in both parameters. Boyden chamber measurements of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) chemotaxis by PMNLs incubated with 10 or 30 micrograms/ml niflumic acid (35 or 106 nmol/ml) or Cu(II)2(niflumate)4 (8 or 23 nmol/ml) were significantly (p < 0.01 to p < 0.001) decreased in dose-related fashions. Chemotaxis of PMNLs from pleuritic rats treated orally with 10 or 30 mg/kg niflumic acid or Cu(II)2(niflumate)4 was significantly (p < 0.001) inhibited by the larger dose of niflumic acid and both doses of Cu(II)2(niflumate)4. Opsonized zymosan (OZ)-stimulated chemiluminescence (CL) of PMNLs from pleuritic rats treated orally with these same doses of niflumic acid or Cu(II)2(niflumate)4 was only significantly (p < 0.05 or p < 0.01 respectively) decreased by the larger doses. Superoxide (O2-) production by these cells was significantly decreased by the larger dose of niflumic acid (p < 0.05) while both doses of Cu(II)2(niflumate)4 produced significant (p < 0.05 to p < 0.01) decreases.(ABSTRACT TRUNCATED AT 250 WORDS)
Roch-Arveiller
M
M
Department of Pharmacology-CNRS URA 595, Hôpital Cochin, Paris, France.
Maman
L
L
Huy
D P
DP
Fontagne
J
J
Giroud
J P
JP
Sorenson
J R
JR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002056:Burns / Q000378:metabolism / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D009544:Niflumic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000633:toxicity; D010998:Pleurisy / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009942:Organometallic Compounds; C095374:tetrakis-2-(3-(trifluoromethyl)phenyl)aminonicotinatodicopper(II); D013481:Superoxides; D009544:Niflumic Acid