College of Veterinary Medicine and Research Institute of Veterinary Medicine Priority Research Institute of NRF, Chungbuk National University, Cheongju 361-763, South Korea.
Reprod Toxicol. 2011 May;31(4):513-8. doi: 10.1016/j.reprotox.2011.02.011. Epub 2011 Mar 5.
Excess hypoxia during embryonic organogenesis leads to developmental abnormalities and postnatal deficits. To determine whether emodin and [6]-gingerol affects hypoxia-induced anomalies during embryonic organogenesis, we cultured embryonic day 8.5 mouse embryos under hypoxic conditions (5% O(2)) for 2 days with or without emodin (1 × 10(-8) μg/mL), [6]-gingerol (1 × 10(-9) μg/mL), and SOD mimetics MnTBAP (1 × 10(2) nM/mL) and then investigated the developmental changes and expression patterns of hypoxia-inducible factor 1α (HIF-1α), cytoplasmic superoxide dismutase (SOD1), and mitochondrial SOD (SOD2) in the embryos. Hypoxic conditions induced various developmental anomalies in the growth stages and remarkably low levels of HIF-1α, SOD1 and SOD2 mRNAs, and SOD activity in the embryos; however, these effects were significantly reversed by treatment with emodin, [6]-gingerol, and MnTBAP, respectively. Our findings indicate that antioxidants such as emodin, [6]-gingerol, and MnTBAP lessen hypoxia-induced embryotoxicities via upregulation of HIF-1α and intracellular SODs.
胚胎器官发生过程中的过度缺氧会导致发育异常和出生后缺陷。为了确定大黄素和[6]-姜酚是否影响胚胎器官发生过程中的缺氧诱导异常，我们将胚胎第 8.5 天的小鼠胚胎在缺氧条件（5% O(2))下培养 2 天，同时加入或不加入大黄素（1 × 10(-8) μg/mL)、[6]-姜酚（1 × 10(-9) μg/mL)、SOD 模拟物 MnTBAP（1 × 10(2) nM/mL)，然后研究胚胎中缺氧诱导因子 1α (HIF-1α)、细胞质超氧化物歧化酶 (SOD1) 和线粒体 SOD (SOD2) 的发育变化和表达模式。缺氧条件诱导了胚胎生长阶段的各种发育异常，并显著降低了 HIF-1α、SOD1 和 SOD2 的 mRNA 水平以及胚胎中的 SOD 活性；然而，这些作用分别被大黄素、[6]-姜酚和 MnTBAP 的处理显著逆转。我们的研究结果表明，抗氧化剂如大黄素、[6]-姜酚和 MnTBAP 通过上调 HIF-1α 和细胞内 SOD 减轻缺氧诱导的胚胎毒性。
