Metal (molybdenum, copper) accumulation and retention in brain, pituitary and other organs of ammonium tetrathiomolybdate-treated sheep
Metal (molybdenum, copper) accumulation and retention in brain, pituitary and other organs of ammonium tetrathiomolybdate-treated sheep
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DOI：
10.1079/bjn19980056
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发表时间：
1998-04-01
影响因子：
3.6
通讯作者：
Parry, NM
中科院分区：
文献类型：
--
作者：
Haywood, S;Dincer, Z;Parry, NM
四硫钼酸铵（TTM）是绵羊慢性铜中毒的首选治疗方法，推荐用于威尔逊氏病。然而，长期效果尚未得到充分评估，一些证据对该药的长期安全性提出了质疑。本研究旨在研究不同品种经ttm处理的绵羊体内Cu和Mo的分布和滞留情况以及Cu的状态。将低铜剑桥羊分为TTM试验组（3.4 mg/kg，每月交替3天皮下注射，连续5个月）和对照组，在疗程结束或7个月后处死。高铜羊由补铜（150 mg/kg）的剑桥组和北罗纳德赛组组成，与未处理的对照组相比，按原方法给予TTM。保留脑、肝、肾、心脏、骨骼肌、垂体、肾上腺、睾丸和卵巢进行金属分析。除肝、肾、骨骼肌外，所有TTM试验组Mo在脑、垂体等各脏器均有积累（P < 0.02），停药后均有保留。高Cu剑桥组Cu含量明显增加（P < 0.02），并保留在小脑和延髓中。脑库。在TTM治疗7个月后，高cu Ronaldsay组Mo浓度呈强正相关（r 0.7）。结论TTM并非全部排出体外，但（Mo）广泛分布并保留在包括脑和垂体在内的许多器官中。此外，TTM可能会将一些移位的过量肝铜（Cu-TTM）重新分配到大脑。这些干扰的后果有待澄清。
Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTM-treated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3.4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, testes and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0.02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0.02) and retained in the cerebellum and medulla oblongata in the TTM-treated high-Cu Cambridge groups. Brain Cu nu. Mo concentrations showed a strongly positive correlation (r 0.7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification.