Angeloni Cristina, Teti Gabriella, Barbalace Maria Cristina, Malaguti Marco, Falconi Mirella, Hrelia Silvana
Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
J Nutr Biochem. 2017 Apr;42:26-36. doi: 10.1016/j.jnutbio.2016.12.017. Epub 2017 Jan 12.
The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating form of estrogen and has a protective role on the cardiovascular system. Recent evidences suggest that gender can influence the response to cardiovascular medications; therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane, present in Brassica vegetables. This study was designed to explore the protective effects of sulforaphane in the presence of 17β-estradiol against HO-induced oxidative stress in primary cultures of rat cardiomyocytes. Interestingly, 17β-estradiol enhanced sulforaphane protective activity against HO-induced cell death with respect to sulforaphane or 17β-estradiol alone as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane ability to counteract oxidative stress, reducing intracellular reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels and increasing the expression of phase II enzymes. Using specific antagonists of estrogen receptor α and β, we observed that these effects are not mediated by estrogen receptors. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the presence of specific inhibitors of these kinases reduced the protective effect of sulforaphane in the presence of 17β-estradiol. Sulforaphane and 17β-estradiol co-treatment counteracted cell morphology alterations induced by HO as evidenced by transmission electron microscopy. Our results demonstrated, for the first time, that estrogens could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones.
与男性相比，女性缺血性心脏病的发病率较低，这表明女性性激素可能在心血管保护方面具有特定作用。17β-雌二醇是绝经前循环中主要的雌激素形式，对心血管系统具有保护作用。最近的证据表明，性别会影响对心血管药物的反应；因此，我们推测性激素也可能调节营养化合物的心脏保护作用，例如十字花科蔬菜中含有的异硫氰酸酯萝卜硫素。本研究旨在探讨在17β-雌二醇存在的情况下，萝卜硫素对大鼠原代心肌细胞中HO诱导的氧化应激的保护作用。有趣的是，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和乳酸脱氢酶测定法测量，与单独使用萝卜硫素或17β-雌二醇相比，17β-雌二醇增强了萝卜硫素对HO诱导的细胞死亡的保护活性。此外，17β-雌二醇增强了萝卜硫素对抗氧化应激的能力，降低了细胞内活性氧和8-羟基-2'-脱氧鸟苷水平，并增加了II期酶的表达。使用雌激素受体α和β的特异性拮抗剂，我们观察到这些作用不是由雌激素受体介导的。否则，ERK1/2和Akt信号通路似乎参与其中，因为这些激酶的特异性抑制剂的存在降低了在17β-雌二醇存在下萝卜硫素的保护作用。透射电子显微镜证明，萝卜硫素和17β-雌二醇联合处理可抵消HO诱导的细胞形态改变。我们的结果首次证明，雌激素可以增强萝卜硫素的保护作用，表明营养功效可能受到性激素的调节。
