Okatani Y, Wakatsuki A, Shinohara K, Kaneda C, Fukaya T
Department of Obstetrics and Gynecology, Kochi Medical School, Oko, Nankoku, Japan.
J Pineal Res. 2001 May;30(4):199-205. doi: 10.1034/j.1600-079x.2001.300402.x.
In preeclampsia, placental production of lipid peroxides is abnormally increased, while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are decreased. Administration of melatonin, a powerful scavenger of oxygen free radicals, also may protect the placenta from free radical-induced damage by increasing the activity of antioxidant enzymes. To test this hypothesis we administered melatonin to pregnant women before they underwent voluntary interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was administered orally at 12:00 hr, and samples of chorion and maternal blood were obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the melatonin concentration in maternal serum and activities of GSH-Px and SOD and levels of melatonin in chorionic homogenates. Melatonin administration was reflected by markedly increased melatonin concentrations in maternal serum and in chorion, with peak levels achieved 1 hr after melatonin administration (serum, 46.87 +/- 10.87 nM/L; chorionic homogenate, 4.36 +/- 1.56 pmol/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic homogenates increased significantly (P < 0.001), with peak levels occurring at 3 hr (51.68 +/- 3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated control subjects). No significant changes in chorionic SOD activity occurred during the 3-hr post-administration period. These results indicate that exogenous melatonin increases GSH-Px activity in the chorion and thereby may protect indirectly against free radical injury. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excessive free radical production, such as intrauterine fetal growth retardation and fetal hypoxia.
在子痫前期，胎盘脂质过氧化物的产生异常增加，而胎盘谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）的活性降低。褪黑素是一种强大的氧自由基清除剂，通过增加抗氧化酶的活性，也可能保护胎盘免受自由基诱导的损伤。为了验证这一假设，我们在妊娠7至9周自愿终止妊娠前，给孕妇服用褪黑素。褪黑素（6毫克）于中午12点口服，在手术时、1、2或3小时后采集绒毛和母血样本。我们测量了母血清中褪黑素的浓度、GSH-Px和SOD的活性以及绒毛匀浆中褪黑素的水平。母血清和绒毛中褪黑素浓度显著增加反映了褪黑素的给药情况，给药后1小时达到峰值水平（血清，46.87±10.87纳摩尔/升；绒毛匀浆，4.36±1.56皮摩尔/毫克蛋白）。在褪黑素给药后1至3小时之间，绒毛匀浆中GSH-Px活性显著增加（P<0.001），在3小时达到峰值水平（51.68±3.22毫微单位/毫克蛋白每分钟，是未治疗对照组GSH-Px活性的137.3%）。给药后3小时内绒毛SOD活性无显著变化。这些结果表明，外源性褪黑素增加了绒毛中GSH-Px的活性，从而可能间接保护免受自由基损伤。褪黑素可能有助于治疗子痫前期以及可能涉及自由基过度产生的其他临床状态，如宫内胎儿生长受限和胎儿缺氧。
