Abstract | OBJECTIVE: DESIGN: MEASUREMENTS AND RESULTS: Treatment of rats with tyrphostin AG 126 (10 mg/kg, 3 mg/kg or 1 mg/kg intraperitoneally, 1 h and 6 h after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Tyrphostin AG 126 also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in the levels of myeloperoxidase and malondialdehyde caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine, poly (ADP-ribose) polymerase (PAR), iNOS, and COX-2 revealed a positive staining in lung, liver and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 were markedly reduced in tissue sections obtained from zymosan-treated rats which had received tyrphostin AG 126. Furthermore, treatment of rats with tyrphostin AG 126 significantly reduced the production of peroxynitrite and of pro-inflammatory cytokines TNF-alpha and IL-1beta. CONCLUSIONS:
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Authors | L Dugo, P K Chatterjee, E Mazzon, M C McDonald, R Di Paola, F Fulia, A P Caputi, C Thiemermann, S Cuzzocrea |
Journal | Intensive care medicine
(Intensive Care Med)
Vol. 28
Issue 6
Pg. 775-88
(Jun 2002)
ISSN: 0342-4642 [Print] United States |
PMID | 12107686
(Publication Type: Journal Article)
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Chemical References |
- Enzyme Inhibitors
- Tyrphostins
- AG 127
- Nitric Oxide
- Zymosan
- Protein-Tyrosine Kinases
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Topics |
- Animals
- Enzyme Inhibitors
(therapeutic use)
- Male
- Models, Animal
- Multiple Organ Failure
(chemically induced, pathology, prevention & control)
- Nitric Oxide
(blood)
- Peritonitis
(chemically induced)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Rats
- Rats, Sprague-Dawley
- Tyrphostins
(therapeutic use)
- Zymosan
(toxicity)
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