RT info:eu-repo/semantics/article
T1 Analysis of mitochondrial function in cell membranes as indicator of tissue vulnerability to drugs in humans
A1 Elexpe, Ane
A1 Sánchez Sánchez, Laura
A1 Tolentino Cortez, Tarson
A1 Astigarraga, Egoitz
A1 Torrecilla, María
A1 Barreda Gómez, Gabriel
K1 Microarrays
K1 Human genetics
K1 Genética humana
K1 Psychopharmacology
K1 Clinical psychology
K1 Psychiatry
K1 Antipsychotic drugs
K1 Antipsicóticos
K1 Drugs
K1 Medicamentos - Efectos secundarios
K1 Cell membranes
K1 Membranas celulares
K1 Mitochondries
K1 Mitocondrias
K1 3209 Farmacología
K1 3211 Psiquiatría
K1 6113 Psicofarmacología
K1 3201.05 Psicología Clínica
AB 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rotenone, but with lower potency, indicating a direct action on mitochondrial complex I. Moreover, nefazodone, a drug withdrawn from the market due to its mitochondrial hepatotoxic effects, evoked the highest superoxide formation in human liver cell membranes, suggesting the potential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.
PB MDPI
SN 2227-9059
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/62573
UL https://uvadoc.uva.es/handle/10324/62573
LA eng
NO Biomedicines, 2022, Vol. 10, Nº. 5, 980
NO Producción Científica
DS UVaDOC
RD 11-jul-2024