Anti-inflammatory effects of carprofen, carprofen enantiomers, and NG-nitro-L-arginine methyl ester in sheep

Zhangrui Cheng Division of Veterinary Pharmacology, Department of Veterinary Preclinical Studies, Veterinary School, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.

Department of Veterinary Basic Sciences, The Royal Veterinary College, Boltons Park, 44 Hawkshead Rd, Hert EN6 1NB, UK.

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Andrea Nolan Division of Veterinary Pharmacology, Department of Veterinary Preclinical Studies, Veterinary School, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.

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Quintin A. McKellar Division of Veterinary Pharmacology, Department of Veterinary Preclinical Studies, Veterinary School, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.
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)

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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