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孕期和哺乳期经口暴露于砷甜菜碱对 Sprague-Dawley 大鼠的影响。

Effects of oral exposure to arsenobetaine during pregnancy and lactation in Sprague-Dawley rats.

机构信息

a Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada , Sir Frederick G. Banting Research Centre, Tunney's Pasture , Ottawa , Ontario , Canada.

出版信息

J Toxicol Environ Health A. 2013;76(24):1333-45. doi: 10.1080/15287394.2013.854715.

Abstract

Arsenobetaine (ASB) is the major form of arsenic (As) in seafood sources such as molluscs and fish. Limited data demonstrated that ASB toxicity in mammals is minimal; however, data on possible reproductive effects are lacking. This study investigated the tissue distribution and developmental effects of ASB during pregnancy, early postnatal life, and development to adulthood. Pregnant rats were randomly assigned to 3 cohorts and gavaged daily from gestational day 8 (GD8) with ASB in deionized water at 0, 0.1, 1, or 10 mg/kg body weight (bw)/d. Cohort 1 dams were sacrificed on GD20 (n = 6 per dose group), cohort 2 dams and pups were sacrificed on postnatal day 13 (PND13; n = 4 dams per dose group), and cohort 3 pups (n = 2 dams per dose group) were sacrificed on PND90. Residue analysis detected significant levels of ASB in livers of cohort 1 dams and lower levels in cohort 1 GD20 fetuses, as well as in cohort 2 male and female offspring, indicating placental transfer from the maternal circulation in utero. Trace amounts of ASB in dams' milk were found only in the 10-mg/kg bw/d dose cohort 2 (PND13), demonstrating that lactational transfer was limited. ASB levels in liver varied during pregnancy, lactation, and postweaning, with levels falling rapidly as these physiological states progress. Although transfer of ASB through the placenta to the fetuses and to a limited extent through milk was confirmed, ASB exposure during pregnancy and lactation appeared to produce no teratogenic or deleterious effects on reproductive development.

摘要

砷甜菜碱(ASB)是贝类和鱼类等海鲜来源中砷(As)的主要形式。有限的数据表明,哺乳动物中 ASB 的毒性最小;然而,关于其可能的生殖毒性的数据尚缺乏。本研究调查了 ASB 在妊娠、产后早期和发育至成年期间的组织分布和发育效应。将怀孕的大鼠随机分为 3 个队列,并从妊娠第 8 天(GD8)开始用去离子水每日灌胃 ASB,剂量分别为 0、0.1、1 或 10 mg/kg 体重(bw)/d。第 1 个队列的母鼠在 GD20 时处死(每组 6 只),第 2 个队列的母鼠和幼鼠在产后第 13 天(PND13)处死(每组 4 只母鼠),第 3 个队列的幼鼠(每组 2 只母鼠)在 PND90 时处死。残留分析在第 1 个队列的母鼠肝脏和第 1 个队列的 GD20 胎鼠中检测到显著水平的 ASB,以及第 2 个队列的雄性和雌性幼鼠中检测到较低水平的 ASB,表明 ASB 从母体循环中通过胎盘转移到宫内胎儿。仅在第 2 个队列(PND13)的 10mg/kg bw/d 剂量组的母鼠乳汁中发现痕量的 ASB,表明乳转移是有限的。在妊娠、哺乳和断奶后期间,母鼠肝脏中的 ASB 水平发生变化,随着这些生理状态的进展,水平迅速下降。尽管通过胎盘向胎儿和在有限程度上通过乳汁转移 ASB 得到了证实,但妊娠和哺乳期的 ASB 暴露似乎对生殖发育没有致畸或有害影响。

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