Abstract | BACKGROUND: METHODS: Rats were subjected to 50 min of supraceliac aortic occlusion. Over a 20-min period, starting 2 min before the release of the aortic clamp, the animals received 2 μL/g of Ringer's lactate solution (RL, n = 5) or an equivalent volume of a solution containing EP (n = 5), benzoyl formate (BF, n = 5), parahydroxyphenyl pyruvate ( PHPP, n = 5) or sodium pyruvate (NaPyr, n = 5). The total dose of each compound was 0.86 mMol/kg. After 1h of reperfusion, we measured ileal mucosal permeability to fluorescein-labeled dextran (mw 4000 Da), liver malondialdehyde (MDA) content, and plasma levels of alanine aminotransferase (ALT) and TNF. Rats in the control group (CT, n = 4) were subjected to laparotomy and surgical isolation of the supraceliac aorta, but not visceral I/R. RESULTS: Ileal mucosal permeability, plasma levels of ALT and TNF, and hepatic MDA content increased significantly in the RL group relative to the CT group. Both EP and BF significantly ameliorated the development of systemic arterial hypotension, mucosal hyperpermeability, and significantly decreased plasma levels of TNF. MDA content was significantly decreased by EP, PHPP, BF, and NaPyr. CONCLUSIONS: In general, EP is more efficacious in this model than is NaPyr. Although more remains to be learned about the pharmacologic differences between EP and pyruvate, one important factor may the greater lipophilicity of the former compound. This insight may permit the development of even more effective cytoprotective and anti-inflammatory agents based on the pyruvoyl moiety.
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Authors | Ruy J Cruz Jr, Tomoyuki Harada, Eizaburo Sasatomi, Mitchell P Fink |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 165
Issue 1
Pg. 151-7
(Jan 2011)
ISSN: 1095-8673 [Electronic] United States |
PMID | 19959189
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents
- Glyoxylates
- Mandelic Acids
- Phenylpyruvic Acids
- Pyruvates
- Tumor Necrosis Factor-alpha
- ethyl pyruvate
- 4-hydroxyphenylpyruvic acid
- phenylglyoxylic acid
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Blood Pressure
(drug effects)
- Cytoprotection
- Disease Models, Animal
- Fluid Therapy
- Glyoxylates
(pharmacology)
- Intestinal Mucosa
(metabolism)
- Ischemia
(drug therapy)
- Lipid Peroxidation
(drug effects)
- Liver
(metabolism)
- Male
- Mandelic Acids
(pharmacology)
- Permeability
- Phenylpyruvic Acids
(pharmacology)
- Pyruvates
(pharmacology, therapeutic use)
- Rats
- Reperfusion Injury
(drug therapy)
- Structure-Activity Relationship
- Tumor Necrosis Factor-alpha
(blood)
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