褪黑素对苯妥英诱发胚胎脑组织氧化性损伤的拮抗作用

Melatonin antagonizes the oxidative damage initiated by phenytoin in embryonic brain

目的 研究褪黑素 (MT)对苯妥英 (Phe)诱发的胚胎脑组织氧化性损伤有无保护作用。方法 妊娠Wistar母鼠于妊娠 (GD11～ 14 )ig 0和 10 0mg·kg- 1Phe ,4 0mg·kg- 1MT及 4 0mg·kg- 1MT +10 0mg·kg- 1Phe ;GD15脱颈椎处死动物 ,测定胎鼠脑组织各种与氧化性损伤有关的指标。结果 妊娠期染毒Phe导致胚胎脑组织H2 O2 水平升高 ,脂质过氧化和蛋白质氧化产物增加 ,超氧化物岐化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性下降 ,总还原型谷胱甘肽(GSH)含量及总抗氧化力降低。妊娠期MT处理减少正常胎鼠脑中H2 O2 及产率 ;同时MT和Phe共同处理可阻断Phe诱发的氧化性损伤 ,GSH耗竭和抗氧化酶活性的下降。结论 MT对Phe诱发的胎鼠脑组织氧化性损伤有一定的拮抗作用。

AIM To study whether there is antagonistic effect of mela tonin (MT) on the oxidative damage initiated by phenytoin (Phe) in embryonic bra in. METHODS Pregnant Wistar rats were administered by gavage on gestation days (GD) 11-14 either 0, 100 mg·kg -1 Phe, 40 mg·kg -1 MT, or 40 mg·kg -1 MT and 100 mg·kg -1 Phe simultaneously. The oxidative damage indices in fetal rat brains were spectrophotometrically analyze d on GD 15. RESULTS An increase in H 2O 2 levels, thiobarbit al acid reactive substance and protein carbonyls, and reduction in reduced gluta thione(GSH) level, activities of superoxide dismutase, catalase a nd glutathione peroxidase; and total antioxidative capacity in the brain of fetal rats were observed 4 d after Phe treatment. In contrast to these effects, decreased H 2O 2 and O÷ 2 levels, normal activities of antioxidative enzymes and GSH level in fetal brain were seen in MT treated rats. Furthermore, repetitive gavages of MT prevented Phe-induced oxidative injuries, depletion o f GSH, decrease of activities of antioxidative enzymes and total antioxidative c apacity. CONCLUSION MT antagonizes the oxidative damage initiated b y phenytoin in embryonic brain.