Amiodarone attenuates apoptosis, but induces phospholipidosis in rat alveolar epithelial cells

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dc.contributor.authorKapatou, E.en
dc.contributor.authorSkyrlas, A.en
dc.contributor.authorAgelaki, M. G.en
dc.contributor.authorPantos, C.en
dc.contributor.authorKolettis, T. M.en
dc.contributor.authorMalamou-Mitsi, V.en
dc.date.accessioned2015-11-24T19:36:46Z
dc.date.available2015-11-24T19:36:46Z
dc.identifier.issn1899-1505-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23936
dc.rightsDefault Licence-
dc.subjectAmiodarone/*pharmacologyen
dc.subjectAnimalsen
dc.subjectApoptosis/*drug effectsen
dc.subjectApoptosis Regulatory Proteins/antagonists & inhibitors/genetics/metabolismen
dc.subjectCaspase 3/antagonists & inhibitors/genetics/metabolismen
dc.subjectCaspase 8/genetics/metabolismen
dc.subjectEpithelial Cells/drug effects/metabolismen
dc.subjectFemaleen
dc.subjectIn Situ Nick-End Labeling/methodsen
dc.subjectLipidoses/chemically induced/metabolismen
dc.subjectLung/cytology/drug effects/metabolismen
dc.subjectPhosphatidylinositol 4,5-Diphosphate/genetics/metabolismen
dc.subjectPhospholipase C gamma/genetics/metabolismen
dc.subjectPhospholipids/*biosynthesisen
dc.subjectPulmonary Alveoli/cytology/*drug effects/metabolismen
dc.subjectRatsen
dc.subjectRats, Wistaren
dc.titleAmiodarone attenuates apoptosis, but induces phospholipidosis in rat alveolar epithelial cellsen
heal.abstractAmiodarone-induced pulmonary toxicity is a serious side-effect, but the underlying molecular mechanisms remain unclear. We examined phospholipidosis and apoptosis in rat alveolar epithelial cells after medium-term oral amiodarone treatment. Amiodarone (30 mg/kg daily, a dosage corresponding to that used clinically) or vehicle was administered by gavage in 33 Wistar rats for two weeks. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL) and the expression of apoptosis- and phospholipidosis-related proteins was measured by immunohistochemistry. Amiodarone decreased phospholipase-C-gamma1 and increased phosphatidylinositol-(4,5)-bisphosphate, resulting in phospholipidosis, evidenced by the appearance of intracellular inclusion bodies with a multi-lamellated interior. Amiodarone exerted two opposite effects on apoptosis; compared to controls, the expression of activated-caspase-8 was higher in treated rats, while the expression of apoptosis inhibitors survivin, Bcl-2 and c-Flip was lower. On the other hand, the expression of activated-caspase-3 was lower after treatment. Overall, amiodarone attenuated apoptosis, evidenced by fewer TUNEL-positive cells. Medium-term oral amiodarone administration induced phospholipidosis in rat alveolar epithelial cells. Although such treatment decreased anti-apoptotic proteins, apoptosis was attenuated via a decrease in the caspase-3 pathway. These findings improve current understanding on the mechanisms underlying amiodarone-induced pulmonary toxicity.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/21224497-
heal.journalNameJ Physiol Pharmacolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2010-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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