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Neutrophils-derived peroxynitrite contributes to acute hyperalgesia and cell influx in zymosan arthritis

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Abstract

We investigated the contribution of neutrophils to joint hyperalgesia and peroxynitrite formation in zymosan arthritis. Rats received 1 mg zymosan intra-articular, and joint hyperalgesia was measured using the rat knee-joint articular incapacitation test. After 6 h, joint exudates were collected by aspiration for the assessment of cell influx, myeloperoxidase activity, and nitrite (as an index of nitric oxide formation) levels. Nitrotyrosine content, used as an index of peroxynitrite formation, was measured in joint exudates, using enzyme-linked immunosorbent assay. A group of rats was rendered neutropenic through the administration of a rabbit anti-rat neutrophil antibody (2 ml kg−1, i.p.) 30 min before injection of 1 mg zymosan intra-articular. Other groups received uric acid (100 or 250 mg kg−1, i.p.), the peroxynitrite scavenger, 30 min before 1 mg zymosan intra-articular. Controls received the vehicle. The significant inhibition of joint hyperalgesia in neutropenic animals was associated to significantly decreased cell influx, myeloperoxidase activity, nitric oxide, and nitrotyrosine levels in the joint exudates, as compared to naive rats. Uric acid administration inhibited both hyperalgesia and cell influx, as compared to controls. Neutrophils are involved in both nitric oxide and peroxynitrite formation in zymosan arthritis, thereby contributing to acute joint hyperalgesia. Scavenging of reactive nitrogen species (e.g. peroxynitrite) inhibits neutrophil migration and joint hyperalgesia in the acute phase of zymosan arthritis in rats.

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Abbreviations

DMARDS:

disease modifying anti-rheumatic drugs

i.art:

intra-articular

L-NAME:

N-nitro-l-arginine methyl ester

LTB4 :

leukotriene B4

MPO:

myeloperoxidase

NO:

nitric oxide

NOS:

nitric oxide synthase

NT:

non-treated

PET:

paw elevation time

PN:

peroxynitrite

RA:

rheumatoid arthritis

SIN-1:

3-Morpholinosydnonimine

SOD:

superoxide dismutase

TMB:

tetramethylbenzene

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Acknowledgement

The authors thank Fundação Cearense de Desenvolvimento Científico e Tecnológico (FUNCAP) and CNPq, Brazil.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Faculty of Medicine of Sobral, Federal University of Ceará, Rua Geraldo Rangel, s/n, Derby, Sobral, Ceará, Brazil

    Mirna M. Bezerra & Virgínia C. C. Girão

  2. Centre for Cardiovascular Biology and Medicine, New Hunt’s House, King’s College London, Guy’s Campus, London, SE1 1UL, UK

    Susan D. Brain, Stan Greenacre & Julie Keeble

  3. Department of Internal Medicine, Federal University of Ceará, Rua Prof. Costa Mendes, 1608, Rodolfo Teófilo, CEP 60416-200, Fortaleza, Ceará, Brazil

    Francisco A. C. Rocha

  4. Faculty of Medicine, Federal University of Ceará, Rua Dr. José Lourenço, 1930, Aldeota, CEP 60115-281, Fortaleza, CE, Brazil

    Francisco A. C. Rocha

Authors
  1. Mirna M. Bezerra
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  2. Susan D. Brain
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  3. Virgínia C. C. Girão
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  4. Stan Greenacre
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  5. Julie Keeble
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  6. Francisco A. C. Rocha
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Correspondence to Francisco A. C. Rocha.

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Bezerra, M.M., Brain, S.D., Girão, V.C.C. et al. Neutrophils-derived peroxynitrite contributes to acute hyperalgesia and cell influx in zymosan arthritis. Naunyn-Schmied Arch Pharmacol 374, 265–273 (2007). https://doi.org/10.1007/s00210-006-0123-9

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  • DOI: https://doi.org/10.1007/s00210-006-0123-9

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