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Synergistic Effect of Nitric Oxide Synthase and Cyclooxygenase Inhibitors on Carrageenan-Induced Paw Edema in Rats

Synergistic Effect of Nitric Oxide Synthase and Cyclooxygenase Inhibitors on Carrageenan-Induced Paw Edema in Rats

Yasue Sakaguchi, Hiroaki Shirahase, Kazuyoshi Kunishiro, Atsuko Ichikawa, Mamoru Kanda, Yoshio Uehara

Arzneimittelforschung. 2006;56(10):695-9.

PMID: 17225565

Abstract:

The present study examined the effects of L-nitroarginine methylester (L-NAME, CAS 50903-99-6), a non-selective nitric oxide synthase (NOS) inhibitor, indometacin (IND, CAS 3305-29-1), a non-selective cyclooxygenase (COX) inhibitor, and a combination of these agents (L-NAME + IND) on carrageenan-induced paw edema for 4 h after the injection of carrageenan in rats. L-NAME at 10 and 30 mg/ kg but not 3 mg/kg (i.p.) decreased paw volume slightly but significantly only at 1 h after the carrageenan injection. IND reduced paw volume slightly at 1 and 3 mg/kg, and markedly at 10 mg/kg (p.o.). A combination of L-NAME and IND at a subthreshold dose (3 mg/kg, i.p. and 1 mg/kg, p.o., respectively) caused a marked reduction of paw edema, which was also confirmed by histopathological examinations. A combination of N-(3-(aminomethyl)benzyl)acetamidine (1400W, CAS 180001-34-7), a selective inhibitor of inducible NOS, and IND at 3 mg/kg, i.p., and 1 mg/kg, p.o., respectively, did not show synergistic anti-inflammatory effects. In conclusion, the combination of non-selective NOS and COX inhibitors had synergistic anti-inflammatory effects on carrageenan-induced paw edema at an early stage, suggesting negative crosstalk between the endogenous NOS-NO and COX-PG pathways in the early stages of acute inflammation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP214358335-A	1400W - CAS 214358-33-5		214358-33-5	Price

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