代谢
研究了反式-[3-14C]肉桂醛在雄性和雌性Fischer 344大鼠以及CD1小鼠体内的代谢情况，通过腹腔注射给予2和250 mg/kg体重的剂量，以及雄性通过口服灌胃给予250 mg/kg的剂量。在两种物种中，给药剂量的约94%在72小时内通过排泄物回收，其中大部分（75-81%）出现在0-24小时的尿液中。在给药后72小时，体内残留的剂量不到2%。尿液中的代谢物通过色谱特性进行鉴定。在两种物种中，主要的尿液代谢物是马尿酸，伴随着3-羟基-3-苯基丙酸、苯甲酸和苯甲酰葡萄糖苷。肉桂酸与甘氨酸形成的结合物仅在鼠标体内大量生成。肉桂醛的氧化代谢基本上遵循肉桂酸的代谢途径，通过类似于脂肪酸的β-氧化。除了肉桂酸和肉桂醛共有的代谢物外，大鼠0-24小时尿液中7%的14C归因于两个新的代谢物，而在小鼠中是三个新的代谢物，其他研究工作已经表明这些新的代谢物来自于肉桂醛代谢的第二条途径，涉及与谷胱甘肽的结合。在大鼠和小鼠中，肉桂醛的排泄模式和代谢轮廓不会因性别、剂量大小和给药途径而有系统地受到影响。数据讨论了其与反式肉桂醛安全性评估的相关性，特别是从高剂量到低剂量的毒性数据外推的有效性或无效性。/反式肉桂醛/
The metabolism of trans-[3-14C]cinnamaldehyde was investigated in male and female Fischer 344 rats and CD1 mice at doses of 2 and 250 mg/kg bw given by ip injection and in males at 250 mg/kg by oral gavage. Some 94% of the administered dose was recovered in the excreta in 72 hr in both species with most (75-81%) present in the 0-24-hr urine. Less than 2% of the administered dose was found in the carcasses at 72 hr after dosing. Urinary metabolites were identified by their chromatographic characteristics. In both species the major urinary metabolite was hippuric acid accompanied by 3-hydroxy-3-phenylpropionic acid, benzoic acid and benzoyl glucuronide. The glycine conjugate of cinnamic acid was formed to a considerable extent only in the mouse. The oxidative metabolism of cinnamaldehyde essentially follows that of cinnamic acid, by beta-oxidation analogous to that of fatty acids. Apart from the metabolites common to cinnamic acid and cinnamaldehyde, 7% of 0-24-hr urinary 14C was accounted for by two new metabolites in the rat and three in the mouse, which have been shown in other work to arise from a second pathway of cinnamaldehyde metabolism involving conjugation with glutathione. The excretion pattern and metabolic profile of cinnamaldehyde in rats and mice are not systematically affected by sex, dose size and route of administration. The data are discussed in terms of their relevance to the safety evaluation of trans-cinnamaldehyde, particularly the validity or otherwise of extrapolation of toxicity data from high to low dose. /trans-Cinnamaldehyde/
来源:Hazardous Substances Data Bank (HSDB)
