Impaired mitochondrial functions contribute to 3-bromopyruvate toxicity in primary rat and mouse hepatocytes
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27530389
DOI
10.1007/s10863-016-9674-8
PII: 10.1007/s10863-016-9674-8
Knihovny.cz E-zdroje
- Klíčová slova
- 3-bromopyruvate, Hepatocyte, Liver, Mitochondria, Toxicity,
- MeSH
- časové faktory MeSH
- hepatocyty cytologie účinky léků ultrastruktura MeSH
- jaterní mitochondrie účinky léků MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- mitochondriální nemoci chemicky indukované patofyziologie MeSH
- myši MeSH
- pyruváty farmakologie toxicita MeSH
- reaktivní formy kyslíku metabolismus MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bromopyruvate MeSH Prohlížeč
- pyruváty MeSH
- reaktivní formy kyslíku MeSH
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.
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