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 language | English (US) |
|---|---|
| Pages (from-to) | 450-459 |
| Number of pages | 10 |
| Journal | Free Radical Biology and Medicine |
| Volume | 24 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1998 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation
AU - Cuzzocrea, Salvatore
AU - Zingarelli, Basilia
AU - Hake, Paul
AU - Salzman, Andrew L.
AU - Szabo, Csaba
PY - 1998/2
Y1 - 1998/2
N2 - 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.
AB - 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.
KW - Carrageenin
KW - Free radicals
KW - Inflammation
KW - Nitric oxide
KW - NO synthase
KW - Peroxynitrite
KW - Prostaglandins
KW - Shock
KW - Superoxide
UR - http://www.scopus.com/inward/record.url?scp=0031975261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031975261&partnerID=8YFLogxK
U2 - 10.1016/S0891-5849(97)00280-3
DO - 10.1016/S0891-5849(97)00280-3
M3 - Article
VL - 24
SP - 450
EP - 459
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 3
ER -