Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition

<p>Abstract</p> <p>Background</p> <p>Curcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction.</p> <p>Methods</p> <p>Diabetes (DM) was induced in rats by streptozotocin (STZ). Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII) were examined by hydroethidine and immunofluorescence, respectively.</p> <p>Results</p> <p>The dilatory response to acetylcholine (ACh) significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP) was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively) of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O₂^●-) production. O₂^●-production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished.</p> <p>Conclusion</p> <p>Therefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.</p

Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells

<p>Abstract</p> <p>Background</p> <p>Zearalenone (ZEA) is a phytoestrogen from <it>Fusarium </it>species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved.</p> <p>Methods</p> <p>Cell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach.</p> <p>Results</p> <p>ZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only <it>ERp29 </it>mRNA transcript increased.</p> <p>Conclusion</p> <p>ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.</p

Свободнорадикальные процессы на отдаленных сроках радиационного воздействия

Free radical status of 9 liquidators of Chernobyl katastrophe consequences was investigated. The level of lipid peroxidation, extra- and intracellular ratio of oxygen active form (OAF) and concentration of calcium ions in the phagocytes in the bronchoalveolar lavage (BAL) and blood were studied. It was found that the above parameters in the blood cells are the same as in those of the healthy people. But the greater formation rate of active radicals in the BAL cells and increased content of lipid peroxidation products and calcium ions was witnessed. According to the data obtained, the activization of free radical processes in the examined patients lungs may be interpreted as the distant results of aerosol radiation damage. Different possible approaches to the treatment of Chernobyl catastrophe liquidators are discussed.Изучен свободнорадикальный статус 9 пациентов—ликвидаторов аварии на Чернобыльской АЭС. Измерены следующие параметры: уровень перекисного окисления липидов, соотношение вне- и внутриклеточной продукции активных форм кислорода и концентрация ионов кальция в фагоцитирующих клетках бронхоальвеолярного лаважа (БАЛ) и крови.Получены данные о том, что исследованные параметры не отличаются от нормальных в клетках крови. В то же время в клетках БАЛ было зарегистрировано усиление внутриклеточной продукции активных форм кислорода, увеличение содержания продуктов ПОЛ и ионов кальция.Представленные результаты позволяют интерпретировать активацию свободнорадикальных процессов в легких обследованных пациентов именно как отдаленный результат аэрозольного радиационного воздействия. Обсуждаются возможные подходы к лечению пациентов—ликвидаторов радиационных аварий