Ischemic stroke is a severe cause of disability and death all over the world. To search for effective therapy for ischemic stroke, PC12 cells damaged by oxygenation and glucose deprivation/restoration were employed to assess the protective effects of inotodiol. As a result, inotodiol can improve the cell viability and attenuate the leakage of lactate dehydrogenase. Meanwhile, inotodiol can prevent oxidative stress by reducing reactive oxygen species generation, decreasing the content of malonic dialdehyde, and increasing the activity of superoxide dismutase. In addition, the dysfunction of mitochondria induced by oxygenation and glucose deprivation/restoration was ameliorated through decreasing the level of intracellular calcium and increasing the mitochondrial membrane potential. At the same time, inotodiol can inhibit PC12 cells apoptosis through downregulation of Caspase-3 and Bax as well as upregulation of Bcl-2. These results reveal inotodiol can protect PC12 cells against the injury induced by oxygenation and glucose deprivation/restoration. This investigation gives promising evidences for the therapy of ischemic stroke.
- Klíčová slova
- inotodiol,
- MeSH
- apoptóza MeSH
- buňky PC12 * patologie účinky léků MeSH
- cévní mozková příhoda * farmakoterapie MeSH
- glukosa MeSH
- kaspasa 3 MeSH
- krysa rodu rattus MeSH
- kyslík MeSH
- laktátdehydrogenasy metabolismus MeSH
- lanosterol analogy a deriváty farmakologie MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- oxidační stres účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- vápníková signalizace účinky léků MeSH
- western blotting MeSH
- Check Tag
- krysa rodu rattus MeSH
The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3-5 and 7-10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5±0.4 μM (8) and 18.5±3.9 μM (9)], breast adenocarcinoma [19.5±2.1 μM (8) and 23.1±4.0 μM (9)] and cervical cancer [24.8±5.3 μM (8) and 29.1±4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4±11.1 μM).
- MeSH
- amidy chemie MeSH
- aminy chemie MeSH
- cholesterol analogy a deriváty chemická syntéza farmakologie MeSH
- cytotoxiny chemická syntéza farmakologie MeSH
- fibroblasty cytologie účinky léků metabolismus MeSH
- lanosterol analogy a deriváty chemická syntéza farmakologie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Metabolismus cholesterolu a jeho prekurzorů byl vyšetřen v prvních dnech po polytraumatu u 70 nemocných. Cholesterolémie nižší než 3,5 mmoUl se vyvinula u všech zraněných, ač nebyla přítomna u nikoho v komrolnt skupině (p > 0,001). Na vzniku hypocholesterolémie se významně podílela hemodiluce během prvních 24 hodin po úrazu, nedostatečná syntéza cholesterolu a jeho prekurzorů a dále spotřeba plazmatického cholesterolu neobjasněným mechanismem. Délka trváni hypocholesterolémie byla průměrně 9±3,2 dnů.
We evaluated cholesterol and its precursors metabolism in 70 patiems within a few days after polytrauma. We observed low serum cholesterol levels (< 3.5 mmoUl) in all the patients, but these low values were not observed in the patients from the comrol group (P > 0.001). The reasons for hypocholesterolaemia were haemodilution during the earliest 24 hours after trauma, low rafe of cholesterol and its precursors synthesis and the consumption of serum cholesterol in an unknown proces. Average time for which hypocholesterolaemia lasted was 9±3.2 days.
