Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina.
Centro de Investigaciones en Psicología y Psicopedagogía (CIPP), Facultad de Psicología y Psicopedagogía, Pontificia Universidad Católica Argentina (UCA), Buenos Aires C1107AFB, Argentina.
Int J Mol Sci. 2024 Nov 12;25(22):12121. doi: 10.3390/ijms252212121.
Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5-10-fold in developing countries. Schizophrenia, cerebral palsy, mental retardation, epilepsy, blindness, and others are among the highly disabling chronic pathologies associated with PA. However, so far, there is no effective therapy to neutralize or reduce PA-induced harm. Selective regulators of estrogen activity in tissues and selective estrogen receptor modulators like raloxifene have shown neuroprotective activity in different pathological scenarios. Their effect on PA is yet unknown. The purpose of this paper is to examine whether raloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model. To study this issue, T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37 °C in a hypoxia chamber with 1% O for 3, 6, 12, and 24 h. Cultures were supplemented with raloxifene 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Raloxifene 100 nM and 10 nM improved cell survival-65.34% and 70.56%, respectively, compared with the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene co-treatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-h oxygen-glucose deprivation followed by 3, 6, and 9 h of reoxygenation, respectively. Therefore, raloxifene improved cell survival and mitochondrial membrane potential and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. In this study, raloxifene protected oxygen-glucose-deprived astrocyte cells, used to mimic hypoxic-ischemic brain injury. Two examiners performed the qualitative assessment in a double-blind fashion.
围产期窒息（PA）是一种临床病症，其特征是出生前、出生时或出生后立即供氧暂停，是神经发育损伤的重要危险因素。在发达国家，其估计发病率为每 1000 例活产儿中有 1 例，而在发展中国家则上升到 5-10 倍。与 PA 相关的高度致残的慢性病理包括精神分裂症、脑瘫、智力迟钝、癫痫、失明等。然而，到目前为止，还没有有效的治疗方法来中和或减少 PA 引起的伤害。雌激素在组织中的选择性调节剂和选择性雌激素受体调节剂，如雷洛昔芬，在不同的病理情况下显示出神经保护活性。它们对 PA 的影响尚不清楚。本文旨在研究雷洛昔芬在氧葡萄糖剥夺/复氧星形胶质细胞模型中是否具有神经保护作用。为了研究这个问题，培养的 T98G 细胞用无葡萄糖 DMEM 培养基处理，并在 37°C 的缺氧室中用 1%O 孵育 3、6、12 和 24 小时。在葡萄糖和氧剥夺以及复氧期间，培养基中添加雷洛昔芬 10 和 100 nM。与对照组相比，雷洛昔芬 100 nM 和 10 nM 分别提高了细胞存活率 65.34%和 70.56%。雷洛昔芬 10 nM 和 100 nM 共同处理可使线粒体膜电位保持 58.9%和 81.57%。雷洛昔芬共同处理可将超氧化物生成减少 72.72%，过氧化氢生成减少 57%。在暴露于 6 小时氧葡萄糖剥夺后再复氧 3、6 和 9 小时的 T98G 细胞中，雷洛昔芬共同处理分别将线粒体质量保持在 47.4%、75.5%和 89%。因此，雷洛昔芬提高了细胞存活率和线粒体膜电位，减少了脂质过氧化和活性氧（ROS）的产生，表明其对线粒体有直接作用。在这项研究中，雷洛昔芬保护了模拟缺氧缺血性脑损伤的氧葡萄糖剥夺星形胶质细胞。两名检查者以双盲方式进行定性评估。
