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治疗动物体内合成代谢剂的代谢命运及其肉类中的残留水平。

Metabolic fate of anabolic agents in treated animals and residue levels in their meat.

作者信息

Hoffmann B, Karg H

出版信息

Environ Qual Saf Suppl. 1976(5):181-91.

PMID:782867
Abstract

Anabolic agents applied in animal production can be classified as sex hormones, as far as one aspect of their biological activity is concerned. In respect to their chemical nature the agents can be divided into three sub-groups: (a) steroids natural to the body (endogenous steroids); (b) steroids foreign to the body; (c) other compounds foreign to the body. After exogenous application (oral or parenteral) metabolism of compounds in group (a), e.g. 17beta-estradiol or testosterone, follows the pathways for the identical endogenous hormones; i.e. enzymatic transformation of the biologically active molecule into less active compounds. Excretion seems to occur predominantly via the feces, followed by the excretion via the urine. Steroids foreign to the body (group [b]) may be simple esters of endogenous steroids (estradiol benzoate, testosterone propionate) or compounds with basically modified steroidal structures, like trenbolone acetate (estra-4, 9, 11-trien-17beta-OH-3one-Ac). After enzymatic cleavage of an ester in the animal, metabolism of natural steroids again follows the endogenous pathways. Other steroids are mainly excreted without changes of the original steroid structure. It has been demonstrated, that compounds applied as esters have a delayed elimination. Anabolic agents of nonsteroidal structure, (group [c]) like stilbene derivatives and zeranol (6-[6, 10-dihydroxy-undecyl] beta-resorcylicacid-mu-lactone) are not, or only to a minor percentage, catabolized in the body. It can be generalized so far, that the fraction of the hormone eliminated in the urine, is in the conjugated from, while the fraction appearing in the feces is in the free form. This is due to enterohepatic circulation, which occurs with both, the intact or catabolized compound. The elimination rate of anabolic agents not only depends on the absorption after oral or parenteral application, which is strongly related to the type of formula---or cleavage of possible esters, but also on the metabolic clearance rate, which is a function of several factors, for example binding to plasma proteins or tissue structures. Differences in the elimination rate between compounds could be attributed to these phenomena. Tissue residue formation not only depends on the elimination rate, but also on other factors like mode of application, formula and withdrawal time. The possibility for their detection is related to the method applied. In cases of adequate treatments of the animals, and with the exception of the implantation site (see below), positive hormone values in tissues (qualitative and quantitative) could only be obtained, when radioimmunoassay techniques with a sensitivity in the low nanogram range were applied...

摘要

就其生物活性的一个方面而言,应用于动物生产的合成代谢剂可归类为性激素。就其化学性质而言,这些药剂可分为三个亚组:(a) 体内天然存在的类固醇(内源性类固醇);(b) 体内外来的类固醇;(c) 体内外来的其他化合物。在经口或肠胃外施用后,(a)组化合物(例如17β-雌二醇或睾酮)的代谢遵循相同内源性激素的代谢途径;即生物活性分子经酶促转化为活性较低的化合物。排泄似乎主要通过粪便进行,其次是通过尿液排泄。体内外来的类固醇(b组)可能是内源性类固醇的简单酯类(苯甲酸雌二醇、丙酸睾酮)或具有基本修饰甾体结构的化合物,如醋酸群勃龙(estra-4,9,11-三烯-17β-羟基-3-酮-醋酸酯)。在动物体内酯键经酶促裂解后,天然类固醇的代谢再次遵循内源性途径。其他类固醇主要在不改变原始类固醇结构的情况下排泄。已证明,以酯类形式施用的化合物消除延迟。非甾体结构的合成代谢剂(c组),如芪衍生物和玉米赤霉醇(6-[6,10-二羟基十一烷基]β-间苯二酚酸-μ-内酯)在体内不被分解代谢,或仅少量被分解代谢。到目前为止,可以概括的是,尿液中消除的激素部分以结合形式存在,而粪便中出现的部分以游离形式存在。这是由于肝肠循环,完整的或已分解代谢的化合物都会发生这种循环。合成代谢剂的消除率不仅取决于经口或肠胃外施用后的吸收情况,这与配方类型或可能的酯键裂解密切相关,还取决于代谢清除率,代谢清除率是几个因素的函数,例如与血浆蛋白或组织结构的结合。化合物之间消除率的差异可归因于这些现象。组织残留的形成不仅取决于消除率,还取决于其他因素,如施用方式、配方和停药时间。检测它们的可能性与所应用的方法有关。在对动物进行适当处理的情况下,除植入部位外(见下文),只有当应用灵敏度在低纳克范围内的放射免疫分析技术时,才能在组织中获得阳性激素值(定性和定量)……

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