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Anti-nociceptive and anti-edematogenic effects of glibenclamide in a model of acute gouty attack in rats

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Abstract

Objective and design

We investigated the effect of glibenclamide on inflammatory parameters in a model of acute gouty attack in rats.

Treatment

Intra-articular injection of 50 μl of monosodium urate (MSU) crystals (1.25 mg/site) was used to induce gout-related inflammation. The effects of glibenclamide (1–10 mg/kg, s.c.) or dexamethasone (8 mg/kg, s.c., positive control) were assessed on several inflammation parameters.

Methods

Spontaneous nociception assessment, edema measurement, total and differential leucocyte counts, interleukin (IL)-1β release, prostaglandin E2 production and determination of blood glucose levels were analyzed. Peritoneal macrophages were incubated with MSU and levels of IL-1β were measured. Statistical significance was assessed by one- or two-way analysis of variance.

Results

Glibenclamide (3 mg/kg) or dexamethasone (8 mg/kg) prevented nociception and edema induced by MSU injection in rats. Glibenclamide did not affect leukocyte infiltration, IL-1β release and PGE2 production, but only reduced IL-1β production by MSU-stimulated macrophages at very high concentration (200 μM). Dexamethasone significantly reduced leukocyte infiltration, IL-1β release and PGE2 production. Glibenclamide reduced whereas dexamethasone increased blood glucose levels of MSU-injected rats.

Conclusions

Glibenclamide reduced nociception and edema, but not leukocyte infiltration, IL-1β release and PGE2 production. However, its substantial effect on nociception and edema suggests that glibenclamide can be an interesting option as an adjuvant treatment for pain induced by acute attacks of gout.

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Acknowledgments

Financial support: CNPq, CAPES, FAPESC, FINEP. The authors wish to thank Regina de Sordi and Karin Scheschowitsch for their expert help with the in vitro experiments and IL-1ß assay.

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Authors and Affiliations

  1. Laboratório de Neurotoxicidade e Psicofarmacologia, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Rosane M. S. dos Santos, Sara M. Oliveira, Cássia R. Silva, Carin Hoffmeister & Juliano Ferreira

  2. Laboratório de Farmacologia do Óxido Nítrico, Programa de Pós-graduação em Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Jamil Assreuy

  3. Department of Pharmacology, Block D/CCB, Universidade Federal de Santa Catarina, Florianopolis, SC, 88040-900, Brazil

    Jamil Assreuy

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  1. Rosane M. S. dos Santos
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  2. Sara M. Oliveira
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  3. Cássia R. Silva
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  4. Carin Hoffmeister
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  6. Jamil Assreuy
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Correspondence to Jamil Assreuy.

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Responsible Editor: Mauro Teixeira.

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dos Santos, R.M.S., Oliveira, S.M., Silva, C.R. et al. Anti-nociceptive and anti-edematogenic effects of glibenclamide in a model of acute gouty attack in rats. Inflamm. Res. 62, 617–625 (2013). https://doi.org/10.1007/s00011-013-0615-2

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  • DOI: https://doi.org/10.1007/s00011-013-0615-2

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