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Beta-estradiol protects against copper-ascorbate induced oxidative damage in goat liver mitochondria in vitro by binding with ascorbic acid.
Life Sciences ( IF 5.2 ) Pub Date : 2020-03-30 , DOI: 10.1016/j.lfs.2020.117596
Arnab K Ghosh 1 , Bharati Bhattacharjee 1 , Sanatan Mishra 2 , Souvik Roy 3 , Aindrila Chattopadhyay 4 , Adrita Banerjee 4 , Debasish Bandyopadhyay 1
Affiliation  

AIMS β-Estradiol (β-E), one of the chemical forms of female gonad hormone exhibited antioxidant efficacy in biochemical system, in vitro. The aim of the study was to investigate whether any other mechanism of protection by β-E to hepatic mitochondria in presence of stressor agent i.e.,a combination of Cu2+ and ascorbic acid is involved. MAIN METHODS Freshly prepared goat liver mitochondria was incubated with stressors and 1 μM β-E and post incubated with the same concentration at 37 °C at pH 7.4. Mitochondrial viability, biomarkers of oxidative stress, activities of Krebs cycle enzymes, mitochondrial membrane potential, Ca2+ permeability were measured. Mitochondrial morphology and binding pattern of β-E with stressors were also studied. KEY FINDINGS Upon incubation of mitochondria with Cu, ascorbic acid and their combination there is a significant decline in activities of four of Krebs cycle enzymes in an uncompetitive manner with a concomitant increase in Ca2+ permeability and membrane potential of inner mitochondrial membrane, which is withdrawn during co-incubation with β-E, but was not reversed during post incubation with the β-E. The final studies on mitochondrial membrane morphology using scanning electron microscope also exhibited damage. Isothermal titration calorimetry data also showed the negative heat change in the mixture of β-E with ascorbic acid and also its combination with Cu2+. SIGNIFICANCE Our results for the first time demonstrated that β-E protects againstCu2+-ascorbate induced oxidative stress by binding with ascorbic acid. The new mechanism of binding of β-E with stress agents may have a future therapeutic relevance.

中文翻译:

β-雌二醇通过与抗坏血酸结合,在体外保护抗坏血酸铜诱导的山羊肝线粒体氧化损伤。

AIMSβ-雌二醇(β-E)是雌性性腺激素的化学形式之一,在体外生化系统中表现出抗氧化功效。该研究的目的是研究在应激源存在下,β-E对肝线粒体的任何其他保护机制,即Cu2 +和抗坏血酸的组合是否涉及。主要方法将新鲜制备的山羊肝线粒体与应激源和1μMβ-E孵育,然后在37℃,pH 7.4下以相同浓度孵育。测量线粒体的活力,氧化应激的生物标志物,克雷布斯循环酶的活性,线粒体膜电位,Ca2 +渗透性。还研究了β-E与应激源的线粒体形态和结合模式。主要发现线粒体与Cu孵育后,抗坏血酸及其组合以非竞争性方式显着降低了四种Krebs循环酶的活性,同时增加了线粒体内膜的Ca2 +渗透性和膜电位,在与β-E共同孵育期间将其撤回,但是在与β-E一起孵育后不会逆转。使用扫描电子显微镜对线粒体膜形态的最终研究也显示出损伤。等温滴定量热法数据还显示,β-E与抗坏血酸的混合物以及与Cu2 +的混合物的负热变化。意义我们的结果首次证明,β-E通过与抗坏血酸结合来防止Cu2 +-抗坏血酸引起的氧化应激。
更新日期:2020-03-30
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