RESUMEN
A dramatic increase in drug-resistant forms of tuberculosis (TB) stimulates a search for novel anti-TB drugs and studies of the drug resistance acquisition. One of the possible causes is a phenotypic resistance or drug tolerance which is not associated with genomic changes. The majority of anti-TB drugs eliminate 99% of MTB cells in 3-5 days, but the remaining subpopulation becomes unsusceptible to treatment and capable for long-term persistence with ability to resuscitate once the external adverse factor is removed. This evasion of the stress factor facilitates selection of resistant forms, thus warranting long-term treatment with at least four antibacterial drugs in TB. The review considers the main mechanisms of bacterial tolerance that are due to alterations in the cell wall, activation of efflux pumps, induction of transcriptional regulons, changes in metabolic flows, and modification of molecular machineries.
Asunto(s)
Antituberculosos , Farmacorresistencia Bacteriana , Tuberculosis , Animales , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidad , Factores de Tiempo , Tuberculosis/tratamiento farmacológico , Tuberculosis/genética , Tuberculosis/metabolismo , Tuberculosis/patologíaRESUMEN
We studied the effect of inhibition of mitochondrial voltage-dependent anion channels with DIDS on radiosensitivity and mitochondrial status of K562 leukemic cells. The number of apoptotic and necrotic cells, mitochondrial transmembrane potential, and mitochondrial mass were evaluated after irradiation of cells in doses of 4 and 12 Gy in the presence and absence of the inhibitor. Inhibition of mitochondrial voltage-dependent anion channels increased radiosensitivity of K562 cells by 50-70% and decreased both mitochondrial transmembrane potential and mitochondrial mass. Inhibitors of voltage-dependent anion channels are promising agents capable of improving the effectiveness of cancer radiotherapy.
Asunto(s)
Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Proteínas de Transporte de Membrana Mitocondrial/antagonistas & inhibidores , Tolerancia a Radiación/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Canales Aniónicos Dependientes del Voltaje/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células K562 , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismoRESUMEN
Bonnecor metabolism in the rat urine was studied. The main metabolites of bonnecor were identified by means of chromatography-mass-spectrometry.