Abstract | PURPOSE: METHODS: Male Wistar rats were treated orally with 0.2, 1, 5, and 50 mg/kg/day farnesol/vehicle for 12 days, respectively. On day 13, the effect of farnesol treatment on cardiac ischemic tolerance and biochemical changes was tested. Therefore, hearts were isolated and subjected either to 30 min coronary occlusion followed by 120 min reperfusion to measure infarct size or to 10 min aerobic perfusion to measure cardiac mevalonate pathway end-products (protein prenylation, cholesterol, coenzyme Q9, coenzyme Q10, dolichol), and 3-nitrotyrosine (oxidative/nitrosative stress marker), respectively. The cytoprotective effect of farnesol was also tested in cardiomyocytes subjected to simulated ischemia/reperfusion. RESULTS:
Farnesol pretreatment decreased infarct size in a U-shaped dose-response manner where 1 mg/kg/day dose reached a statistically significant reduction (22.3±3.9% vs. 40.9±6.1% of the area at risk, p<0.05). Farnesol showed a similar cytoprotection in cardiomyocytes. The cardioprotective dose of farnesol (1 mg/kg/day) significantly increased the marker of protein geranylgeranylation, but did not influence protein farnesylation, cardiac tissue cholesterol, coenzyme Q9, coenzyme Q10, and dolichol. While the cardioprotective dose of farnesol did not influence 3-nitrotyrosine, the highest dose of farnesol (50 mg/kg/day) tested did not show cardioprotection, however, it significantly decreased cardiac 3-nitrotyrosine. CONCLUSIONS:
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Authors | Gergő Szűcs, Zsolt Murlasits, Szilvia Török, Gabriella F Kocsis, János Pálóczi, Anikó Görbe, Tamás Csont, Csaba Csonka, Péter Ferdinandy |
Journal | Cardiovascular drugs and therapy
(Cardiovasc Drugs Ther)
Vol. 27
Issue 4
Pg. 269-77
(Aug 2013)
ISSN: 1573-7241 [Electronic] United States |
PMID | 23673412
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cardiotonic Agents
- Dolichols
- Ubiquinone
- 3-nitrotyrosine
- Tyrosine
- Farnesol
- Cholesterol
- Mevalonic Acid
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Topics |
- Animals
- Animals, Newborn
- Cardiotonic Agents
(pharmacology, therapeutic use)
- Cell Survival
(drug effects)
- Cells, Cultured
- Cholesterol
(metabolism)
- Dolichols
(metabolism)
- Farnesol
(pharmacology, therapeutic use)
- Male
- Mevalonic Acid
(metabolism)
- Myocardial Reperfusion Injury
(drug therapy, metabolism, pathology)
- Myocardium
(metabolism, pathology)
- Myocytes, Cardiac
(drug effects)
- Protein Prenylation
(drug effects)
- Rats
- Rats, Wistar
- Tyrosine
(analogs & derivatives, metabolism)
- Ubiquinone
(metabolism)
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