Central and peripheral benzodiazepine ligands prevent mitochondrial damage induced by noise exposure in the rat myocardium: an ultrastructural study.
Noise represents an environmental stress factor affecting several organs and apparatuses, including the cardiovascular system. In experimental animals undergoing noise exposure, subcellular myocardial changes have been reported, especially at the mitochondrial level. In previous studies we found that diazepam, acting at both central and peripheral benzodiazepine receptors, prevented the onset of this myocardial damage. In the present study, we investigated the specific role played by central and/or peripheral benzodiazepine receptors in preventing noise-induced myocardial alterations. In particular, the effect of clonazepam as a selective ligand for central sites, in comparison with the efficacy of ligands selective for peripheral sites, such as Ro 5-4864 and PK-11195, was evaluated. Rats were pretreated with the test drugs 30 min before exposure to noise for 6 or 12 hr and then sacrificed. After fixing, samples of right atrium and ventricle were taken and processed for either transmission or scanning electron microscopy. After 6 hr of noise exposure, only the atrium exhibited significant mitochondrial alterations, whereas after 12 hr both atrium and ventricle were damaged. As expected, diazepam prevented noise-induced mitochondrial injury at both 6 and 12 hr. By contrast, clonazepam was effective only after 6 hr. The peripheral ligand PK-11195 attenuated mitochondrial damage at both 6 and 12 hr, whereas Ro 5-4864 was effective only after 12 hr. In the present study, we confirm that noise exposure induces mitochondrial damage in the rat myocardium. Drugs acting at both central and peripheral benzodiazepine receptors significantly prevent this damage. Differences in the amount and in the duration of the protective effect might depend on variability in the potency and in the pharmacokinetics of the specific drugs.
Department of Human Morphology and Applied Biology, Faculty of Medicine, University of Pisa, Italy. m.gesi@anist.med.unipi.it
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Gesi
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Riva
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Soldani
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Fornai
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Natale
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Pellegrini
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Paparelli
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure*; D009206:Myocardium / Q000648:ultrastructure*; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001570:Benzodiazepinones; D018757:GABA Modulators; D007546:Isoquinolines; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195