Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation

Salvatore Cuzzocrea, Basilia Zingarelli, Paul Hake, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

In vitro studies have demonstrated that mercaptoethylguanidine (MEG), a selective inhibitor of the reducible NO synthase (iNOS) is also effective as a scavenger of peroxynitrite (a potent cytotoxic oxidant produced by the reaction of NO and superoxide). In the present study, we evaluated the antiinflammatory potential of MEG treatment in two models of acute inflammation (carrageenan-induced paw edema and pleurisy), where oxyradicals, NO, and peroxynitrite play a crucial role in the inflammatory process. Our data show that MEG (given at 25 μg/paw in the paw edema model or 10 mg/kg in the pleurisy model) inhibits the inflammatory response (paw swelling, pleural exudate formation, mononuclear cell infiltration, histological injury) in both models. Furthermore, MEG reduced nitrite/nitrite concentrations in the exudate and reduced the activity of the inducible isoform of NO synthase in the lung ex vivo MEG also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. Taken together the present results demonstrate that MEG exerts potent antiinflammatory effects. Part of these antiinflammatory effects may be related to an inhibition of the expression/activity of the inducible NO synthase another part may be related to oxyradical and peroxynitrite scavenging.

Original languageEnglish (US)
Pages (from-to)450-459
Number of pages10
JournalFree Radical Biology and Medicine
Volume24
Issue number3
DOIs
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Carrageenan
Nitric Oxide Synthase
Anti-Inflammatory Agents
Inflammation
Pleurisy
Exudates and Transudates
Nitrites
Edema
Scavenging
Infiltration
Oxidants
Superoxides
Swelling
2-mercaptoethylguanidine
Protein Isoforms
Tissue
Lung
Wounds and Injuries

Keywords

  • Carrageenin
  • Free radicals
  • Inflammation
  • Nitric oxide
  • NO synthase
  • Peroxynitrite
  • Prostaglandins
  • Shock
  • Superoxide

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. / Cuzzocrea, Salvatore; Zingarelli, Basilia; Hake, Paul; Salzman, Andrew L.; Szabo, Csaba.

In: Free Radical Biology and Medicine, Vol. 24, No. 3, 02.1998, p. 450-459.

Research output: Contribution to journalArticle

Cuzzocrea, Salvatore ; Zingarelli, Basilia ; Hake, Paul ; Salzman, Andrew L. ; Szabo, Csaba. / Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. In: Free Radical Biology and Medicine. 1998 ; Vol. 24, No. 3. pp. 450-459.
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