The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats
The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats
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DOI：
10.1016/j.reprotox.2004.07.006
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发表时间：
2004-12-01
影响因子：
3.3
通讯作者：
Levine, BS
中科院分区：
文献类型：
--
作者：
Lyubimov, AV;Smith, JA;Levine, BS
基于其螯合铜的能力，TTM正在研究作为癌症治疗的抗血管生成剂。本研究的目的是评价TTM的毒性和补充铜对雄性和雌性CD（R）大鼠生殖能力的保护作用。通过管饲法给予0、1、4和12 mg/kg/天剂量，并补充铜（110 mg/kg饲料）。在任何雌性剂量组中，对发情周期或生殖指数或母体毒性均无影响。给予12 mg/kg/天剂量的雄性大鼠显示体重增加和摄食量显著降低，并出现贫血。在所有雄性剂量组中，血清铜蓝蛋白水平呈剂量依赖性降低。仅在12 mg/kg/天剂量下发生附睾重量、精子计数和精子活力降低、精子形态异常以及睾丸和附睾组织病理学变化。膳食铜补充剂可预防12 mg/kg/天TTM对精子产生的不良影响。(C)2004年爱思唯尔公司All rights reserved.
Based on its ability to chelate copper, TTM is being studied as an antiangiogenic agent for cancer therapy. The purpose of this study was to evaluate the toxicity of TTM and the protection of copper supplementation on the reproductive capability of male and female CD(R) rats. Doses of 0, 1, 4, and 12 mg/kg/day with copper supplementation (110 mg/kg of diet) were given by gavage. There were no effects on the estrous cycle or reproductive indices, or maternal toxicity in any female dose group. Male rats given 12 mg/kg/day showed significant decreases in body weight gains and food consumption, and anemia. Serum ceruloplasmin levels were dose-dependently decreased in all male dose groups. Reduced epididymal weights, sperm counts, and sperm motility, sperm morphologic abnormalities and histopathologic changes in testis and epididymis occurred only at 12 mg/kg/day. Dietary copper supplementation prevented the adverse sperm effects produced by 12 mg/kg/day of TTM. (C) 2004 Elsevier Inc. All rights reserved.