Reynolds W A, Stegink L D, Filer L J, Renn E
Anat Rec. 1980 Sep;198(1):73-85. doi: 10.1002/ar.1091980106.
Infant monkeys received 2 gm/kg body weight of aspartame (APM) or 2 gm/kg body weight APM plus 1 gm/kg body weight monosodium glutamate (MSG) by gastric tube. Blood samples were obtained at intervals over the ensuing 4 hours and analyzed for amino acid levels. At this time, each infant was perfused with glutaraldehyde. The hypothalamus was embedded in plastic and then serially sectioned at 1 mu. Hypothalamic morphology was normal in all eight infants given 2 gm/kg body weight APM and in the six infants given 2 gm/kg body weight APM plus 1 gm/kg body weight MSG. By light microscopy, no pycnotic nuclei, neuronal degeneration, or dendritic swelling was noted. In both experimental and control brains, localized areas of poor perfusion exhibited abnormal morphology. Elevated plasma levels of aspartate, glutamate, and phenylalanine indicated that the test compounds were administered and absorbed. Variable rates of absorption were evident, probably due to the necessity of administering APM as a slurry, due to its low solubility. On the basis of blood absorption curves, it appears that infant monkeys metabolize aspartate and glutamate and phenylalanine somewhat more rapidly than man. It is concluded that APM given alone or with MSG, in large acute doses, does not result in hypothalamic damage in the newborn monkey.
给幼猴经胃管灌胃2克/千克体重的阿斯巴甜(APM)或2克/千克体重的APM加1克/千克体重的味精(MSG)。在随后的4小时内定期采集血样并分析氨基酸水平。此时,对每只幼猴进行戊二醛灌注。将下丘脑包埋在塑料中,然后以1微米的厚度连续切片。在给予2克/千克体重APM的所有8只幼猴以及给予2克/千克体重APM加1克/千克体重MSG的6只幼猴中,下丘脑形态均正常。通过光学显微镜观察,未发现固缩核、神经元变性或树突肿胀。在实验脑和对照脑中,局部灌注不良区域均表现出异常形态。血浆中天冬氨酸、谷氨酸和苯丙氨酸水平升高表明受试化合物已给药并被吸收。由于APM溶解度低,需制成混悬液给药,故吸收速率存在差异。根据血吸收曲线,幼猴对天冬氨酸、谷氨酸和苯丙氨酸的代谢似乎比人类稍快。得出的结论是,大剂量急性单独给予APM或与MSG联合给予,不会导致新生猴下丘脑损伤。