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Título
Analysis of mitochondrial function in cell membranes as indicator of tissue vulnerability to drugs in humans
Autor
Año del Documento
2022
Editorial
MDPI
Descripción
Producción Científica
Documento Fuente
Biomedicines, 2022, Vol. 10, Nº. 5, 980
Resumen
Drug side effects are one of the main reasons for treatment withdrawal during clinical trials. Reactive oxygen species formation is involved in many of the drug side effects, mainly by interacting with the components of the cellular respiration. Thus, the early detection of these effects in the drug discovery process is a key aspect for the optimization of pharmacological research. To this end, the superoxide formation of a series of drugs and compounds with antidepressant, antipsychotic, anticholinergic, narcotic, and analgesic properties was evaluated in isolated bovine heart membranes and on cell membrane microarrays from a collection of human tissues, together with specific inhibitors of the mitochondrial electron transport chain. Fluphenazine and PB28 promoted similar effects to those of rotenone, but with lower potency, indicating a direct action on mitochondrial complex I. Moreover, nefazodone, a drug withdrawn from the market due to its mitochondrial hepatotoxic effects, evoked the highest superoxide formation in human liver cell membranes, suggesting the potential of this technology to anticipate adverse effects in preclinical phases.
Materias (normalizadas)
Microarrays
Human genetics
Genética humana
Psychopharmacology
Clinical psychology
Psychiatry
Antipsychotic drugs
Antipsicóticos
Drugs
Medicamentos - Efectos secundarios
Cell membranes
Membranas celulares
Mitochondries
Mitocondrias
Materias Unesco
3209 Farmacología
3211 Psiquiatría
6113 Psicofarmacología
3201.05 Psicología Clínica
ISSN
2227-9059
Revisión por pares
SI
Patrocinador
Ministerio de Economía y Competitividad - (grant DIN2019-010902)
Gobierno Vasco, Departamento de Desarrollo Económico, Sostenibilidad y Medio Ambiente - (grant Bikaintek: 48-AF-W2-2019-00007)
Gobierno Vasco, Departamento de Desarrollo Económico, Sostenibilidad y Medio Ambiente - (grant Bikaintek: 48-AF-W2-2019-00007)
Version del Editor
Propietario de los Derechos
© 2022 The Authors
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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