Kotch L E, Chen S Y, Sulik K K
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Teratology. 1995 Sep;52(3):128-36. doi: 10.1002/tera.1420520304.
To investigate the possibility of a free radical mechanism for ethanol-induced teratogenesis, gestational day 8 mouse embryos were exposed for 6 hr in whole embryo culture to a teratogenic dosage of ethanol alone (500 mg%) or in conjunction with an antioxidant, superoxide dismutase (SOD; 300 U/ml). For subsequent analysis, some embryos were examined at the end of this 6-hr period, while others were removed to control medium and cultured for an additional time period. Ethanol exposure resulted in increased superoxide anion generation and increased lipid peroxidation (as noted 6 hr after initial ethanol exposure) and in excessive cell death (as noted 12 hr after initial exposure) in the embryos. Following a total of 36 hr in culture, a high incidence of malformation, including failure of the anterior neural tube to close in 63% of the ethanol-exposed embryos, was noted. The ethanol-induced superoxide anion generation, lipid peroxidation, excessive cell death, and dysmorphogenesis were diminished in embryos co-treated with SOD, suggesting that the teratogenicity of ethanol is mediated, at least in part, by free radical damage.
为研究乙醇诱导致畸作用的自由基机制的可能性，将妊娠第8天的小鼠胚胎在全胚胎培养中暴露于致畸剂量的乙醇（500mg%）单独作用或与抗氧化剂超氧化物歧化酶（SOD；300U/ml）联合作用6小时。为进行后续分析，一些胚胎在这6小时结束时进行检查，而其他胚胎则转移至对照培养基中并再培养一段时间。乙醇暴露导致胚胎中超氧阴离子生成增加、脂质过氧化增加（在最初乙醇暴露6小时后观察到）以及细胞过度死亡（在最初暴露12小时后观察到）。在总共培养36小时后，观察到高畸形发生率，包括63%乙醇暴露胚胎中前神经管闭合失败。与SOD共同处理的胚胎中，乙醇诱导的超氧阴离子生成、脂质过氧化、细胞过度死亡和畸形发生均减少，这表明乙醇的致畸性至少部分是由自由基损伤介导的。
