Anti-inflammatory effects of carprofen, carprofen enantiomers, and NG-nitro-L-arginine methyl ester in sheep
Department of Veterinary Basic Sciences, The Royal Veterinary College, Boltons Park, 44 Hawkshead Rd, Hert EN6 1NB, UK.
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Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Penicuik, EH26 0PZ, UK.
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Abstract
Objective—To assess anti-inflammatory effects of carprofen (CPF), CPF enantiomers, and NG-nitro-L-arginine methyl ester (L-NAME) in sheep.
Animals—8 sheep.
Procedure—Sheep with SC tissue cages were used. After intracaveal injection of 1% carrageenan, sheep were given single doses of racemic (Rac; 50:50 mixture of S[+] and R[–] enantiomers)-CPF (4.0 mg/kg), R(–)CPF (2.0 mg/kg), S(+)CPF (2.0 mg/kg), L-NAME (25 mg/kg), and placebo (PLB) IV in a crossover design.
Results—Rac-CPF and S(+)CPF inhibited serum thromboxane2 (TXB2) and exudate prostaglandin (PG)E2 generation significantly for 32 hours. Maximal inhibitory effect for serum TXB2 was 79 ± 3% for Rac- CPF and 68 ± 6% for S(+)CPF. The Rac-CPF and S(+)CPF induced 50 to 98% reversible inhibitory effect for exudate PGE2 generation during a 4- to 32- hour period. The R(–)CPF and L-NAME attenuated serum TXB2 generation significantly. The R(–)CPF did not affect exudate PGE2 production, whereas L-NAME potentiated exudate, PGE2 generation by 30% during 4 to 32 hours. The S(+)CPF and L-NAME increased leukotriene B4 generation and WBC recruitment in exudate although significance was achieved only at a few time points. Increase in skin temperature over inflammatory cages was effectively inhibited by Rac- CPF and S(+)CPF but not by R(–)CPF.
Conclusion and Clinical Relevance—Carprofen is a potent cyclooxygenase inhibitor in vivo in sheep, and its anti-inflammatory effects are attributable only to S(+)CPF in Rac-CPF. Nitric oxide may enhance eicosanoid production and accelerate the acute inflammatory process. (Am J Vet Res 2002;63: 782–788)
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