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Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat.

Abstract：

BACKGROUND AND PURPOSE:Recent findings suggest that the noxious gas H(2)S is produced endogenously, and that physiological concentrations of H(2)S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H(2)S to modulate carrageenan-induced synovitis in the rat knee. EXPERIMENTAL APPROACH:Synovitis was induced in Wistar rats by intra-articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H(2)S formation (DL-propargylglycine) or an H(2)S donor [Lawesson's reagent (LR)]. KEY RESULTS:Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3-NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters. CONCLUSIONS AND IMPLICATIONS:Whereas exogenous H(2)S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect, locally produced H(2)S exerts little immunomodulatory effect. These data further support the development and use of H(2)S donors as potential alternatives (or complementary therapies) to the available anti-inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Ekundi-Valentim E,Santos KT,Camargo EA,Denadai-Souza A,Teixeira SA,Zanoni CI,Grant AD,Wallace J,Muscará MN,Costa SK

doi

10.1111/j.1476-5381.2010.00640.x

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

1463-74

issue

eissn

0007-1188

issn

1476-5381

pii

BPH640

journal_volume

159

pub_type

杂志文章

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Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat.