Analysis of Mitochondrial Function in Cell Membranes as Indicator of Tissue Vulnerability to Drugs in Humans

Biomedicines

María Torrecilla¹  Laura Sánchez-Sánchez²  Egoitz Astigarraga²  Gabriel Barreda-Gómez²  Tarson Tolentino-Cortez²  Ane Elexpe² 

[1] Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Leioa, Spain;Research and Development Department, IMG Pharma Biotech S.L, 48160 Derio, Spain;

关键词: microarray;    superoxide;    antipsychotic;    mitochondria;   

DOI  :  10.3390/biomedicines10050980

来源: DOAJ

【 摘 要 】

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rotenone, but with lower potency, indicating a direct action on mitochondrial complex I. Moreover, nefazodone, a drug withdrawn from the market due to its mitochondrial hepatotoxic effects, evoked the highest superoxide formation in human liver cell membranes, suggesting the potential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.

【 授权许可】

Unknown