Sobotka 2016 J Bioenerg Biomembr
|Sobotka O, Endlicher R, Drahota Z, Kučera O, Rychtrmoc D, Raad M, Hakeem K, Červinková Z (2016) Impaired mitochondrial functions contribute to 3-bromopyruvate toxicity in primary rat and mouse hepatocytes. J Bioenerg Biomembr 48:363-73.|
Abstract: A compound with promising anticancer properties, 3-bromopyruvate (3-BP) is a synthetic derivative of a pyruvate molecule; however, its toxicity in non-malignant cells has not yet been fully elucidated. Therefore, we elected to study the effects of 3-BP on primary hepatocytes in monolayer cultures, permeabilized hepatocytes and isolated mitochondria. After a 1-h treatment with 100 μM 3-BP cell viability of rat hepatocytes was decreased by 30 % as measured by the WST-1 test (p < 0.001); after 3-h exposure to ≥200 μM 3-BP lactate dehydrogenase leakage was increased (p < 0.001). Reactive oxygen species production was increased in the cell cultures after a 1-h treatment at concentrations ≥100 μmol/l (p < 0.01), and caspase 3 activity was increased after a 20-h incubation with 150 μM and 200 μM 3-BP (p < 0.001). This toxic effect of 3-BP was also proved using primary mouse hepatocytes. In isolated mitochondria, 3-BP induced a dose- and time-dependent decrease of mitochondrial membrane potential during a 10-min incubation both with Complex I substrates glutamate + malate or Complex II substrate succinate, although this decrease was more pronounced with the latter. We also measured the effect of 3-BP on respiration of isolated mitochondria. ADP-activated respiration was inhibited by 20 μM 3-BP within 10 min. Similar effects were also found in permeabilized hepatocytes of both species.
• Keywords: 3-bromopyruvate, Hepatocyte, Liver, Mitochondria, Toxicity
• O2k-Network Lab: CZ Hradec Kralove Cervinkova Z
Labels: MiParea: Respiration, mt-Membrane, Pharmacology;toxicology
Stress:Cell death, Oxidative stress;RONS Organism: Mouse, Rat Tissue;cell: Liver Preparation: Intact cells, Permeabilized cells, Homogenate, Isolated mitochondria Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase
Coupling state: LEAK, OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k