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Rosiglitazone Does Not Show Major Hidden Cardiotoxicity in Models of Ischemia/Reperfusion but Abolishes Ischemic Preconditioning-Induced Antiarrhythmic Effects in Rats In Vivo.
Weber, Bennet Y; Brenner, Gábor B; Kiss, Bernadett; Gergely, Tamás G; Sayour, Nabil V; Tian, Huimin; Makkos, András; Görbe, Anikó; Ferdinandy, Péter; Giricz, Zoltán.
Afiliación
  • Weber BY; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Brenner GB; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Kiss B; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Gergely TG; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Sayour NV; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Tian H; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Makkos A; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Görbe A; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
  • Ferdinandy P; Pharmahungary Group, H-6722 Szeged, Hungary.
  • Giricz Z; MTA-SE System Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.
Pharmaceuticals (Basel) ; 15(9)2022 Aug 26.
Article en En | MEDLINE | ID: mdl-36145276
Clinical observations are highly inconsistent with the use of the antidiabetic rosiglitazone regarding its associated increased risk of myocardial infarction. This may be due to its hidden cardiotoxic properties that have only become evident during post-marketing studies. Therefore, we aimed to investigate the hidden cardiotoxicity of rosiglitazone in ischemia/reperfusion (I/R) injury models. Rats were treated orally with either 0.8 mg/kg/day rosiglitazone or vehicle for 28 days and subjected to I/R with or without cardioprotective ischemic preconditioning (IPC). Rosiglitazone did not affect mortality, arrhythmia score, or infarct size during I/R. However, rosiglitazone abolished the antiarrhythmic effects of IPC. To investigate the direct effect of rosiglitazone on cardiomyocytes, we utilized adult rat cardiomyocytes (ARCMs), AC16, and differentiated AC16 (diffAC16) human cardiac cell lines. These were subjected to simulated I/R in the presence of rosiglitazone. Rosiglitazone improved cell survival of ARCMs at 0.3 µM. At 0.1 and 0.3 µM, rosiglitazone improved cell survival of AC16s but not that of diffAC16s. This is the first demonstration that chronic administration of rosiglitazone does not result in major hidden cardiotoxic effects in myocardial I/R injury models. However, the inhibition of the antiarrhythmic effects of IPC may have some clinical relevance that needs to be further explored.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Pharmaceuticals (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Pharmaceuticals (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza