Abstract | OBJECTIVE:
Melatonin may attenuate organ damage via direct antioxidative properties, and was recently demonstrated to reduce cardiac and hepatic injury through receptor-dependent effects. However, the relevance of an isolated activation of melatonin receptors for organ protection, excluding direct antioxidant effects, has not been established yet. This study was designed to investigate whether therapy with melatonin receptor agonist and hypnotic substance ramelteon may improve liver function, hepatic perfusion, and hepatic integrity after hemorrhagic shock in rat. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 10 per group). INTERVENTIONS: MEASUREMENTS AND MAIN RESULTS: In vitro, ramelteon displayed no relevant antioxidant capacity in an 2,2'-Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assay, compared with melatonin. In vivo, liver function was assessed by plasma disappearance rate of indocyanine green, and intravital microscopy was performed for evaluation of hepatic perfusion index, nicotinamide adenine dinucleotide phosphate autofluorescence, and hepatic integrity. Compared with vehicle controls, ramelteon therapy significantly improved plasma disappearance rate of indocyanine green (7.89 +/- 2.12% vs. 13.67 +/- 2.51%; p = 0.006), hepatic perfusion index (352.04 +/- 111.78 pl/sec/mm vs. 848.81 +/- 181.38 pl/sec/mm; p = 0.002), nicotinamide adenine dinucleotide phosphate autofluorescence and hepatocellular injury. Coadministration of luzindole abolished the protective effect of ramelteon with respect to liver function and nicotinamide adenine dinucleotide phosphate autofluorescence. CONCLUSIONS:
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Authors | Alexander M Mathes, Darius Kubulus, Lina Waibel, Julia Weiler, Paul Heymann, Beate Wolf, Hauke Rensing |
Journal | Critical care medicine
(Crit Care Med)
Vol. 36
Issue 10
Pg. 2863-70
(Oct 2008)
ISSN: 1530-0293 [Electronic] United States |
PMID | 18766086
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Indenes
- Receptors, Melatonin
- Tryptamines
- luzindole
- ramelteon
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Topics |
- Analysis of Variance
- Animals
- Disease Models, Animal
- Indenes
(pharmacology)
- Infusions, Intravenous
- Liver Circulation
(drug effects, physiology)
- Liver Diseases
(etiology, prevention & control)
- Liver Function Tests
- Male
- Probability
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Receptors, Melatonin
(drug effects)
- Sensitivity and Specificity
- Shock, Hemorrhagic
(complications, drug therapy, physiopathology)
- Tryptamines
(pharmacology)
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