Emodin and [6]-gingerol lessen hypoxia-induced embryotoxicities in cultured mouse whole embryos via upregulation of hypoxia-inducible factor 1α and intracellular superoxide dismutases.

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.