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Effect of dipyrone, L-NAME and L-arginine on endotoxin-induced rat paw edema
J F Fracasso1, R L Nunes-de-Souza, C E Teixeira
1Departamento de Princípios Ativos Naturais e Toxicologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP, Brasil. fracasso@boldo.fcf.ar.unesp.br
Abstract:
Paw edema was induced in male Wistar rats (200-250 g) by intraplantar (ipl) administration of 2.5 micrograms endotoxin (Etx). Etx, like carrageenin, produced two distinct edema formation phases, an early phase (75 min) followed by a late phase (7 h). We showed that the edema formation in the early phase was antagonized by dipyrone (80 mg/kg, i.p.) and indomethacin (1 mg/kg, i.p.) by 52% and 55%, respectively, and that the late phase was resistant to these drugs. These results suggest that in the early phase prostaglandins appear to be involved in the process. However, the activation of the kinin cascade leading to the release of other mediators may be involved in the increase of edema in the late phase. To test this hypothesis, we investigated whether the release of nitric oxide (NO) is involved in the mechanism of endotoxin-induced rat paw edema during the late phase, using N omega-nitro-L-arginine methyl ester (L-NAME) (50 micrograms, ipl) as inhibitor of NO synthase and L-arginine (1 mg, ipl) as substrate of NO synthase. The paw edema induced by Etx was inhibited by L-NAME by 56% and increased by L-arginine by 81%. Furthermore, L-arginine given in combination with L-NAME completely reversed the inhibition of Etx-induced edema produced by L-NAME. These results support the hypothesis that in the late phase NO production is associated with the edema evoked by Etx.
Insights
Endotoxin-induced paw edema in rats involves two phases. Early phase edema is prostaglandin-dependent, while the late phase is mediated by nitric oxide (NO) production.
Area of Science:
- Pharmacology
- Inflammation Research
- Immunology
Background:
- Paw edema is a common model for studying inflammation.
- Endotoxin induces a biphasic inflammatory response in rat paws.
- Early inflammatory mediators differ from those in later stages.
Purpose of the Study:
- To investigate the mediators involved in the early and late phases of endotoxin-induced paw edema.
- To determine the role of prostaglandins and nitric oxide (NO) in this inflammatory model.
Main Methods:
- Paw edema was induced in Wistar rats using intraplantar endotoxin (Etx).
- The effects of dipyrone and indomethacin on early phase edema were assessed.
- The role of nitric oxide (NO) in the late phase was evaluated using N-omega-nitro-L-arginine methyl ester (L-NAME) and L-arginine.
Main Results:
- Early phase edema was significantly reduced by dipyrone and indomethacin, suggesting prostaglandin involvement.
- Late phase edema was inhibited by L-NAME (a nitric oxide synthase inhibitor) by 56%.
- L-arginine (a NO precursor) administration increased edema by 81% and reversed L-NAME's inhibitory effect.
Conclusions:
- Prostaglandins are key mediators in the early phase of endotoxin-induced paw edema.
- Nitric oxide (NO) production plays a significant role in the late phase of this inflammatory response.
- Targeting NO pathways may offer therapeutic strategies for managing late-stage inflammatory edema.