Batshaw M L, Hyman S L, Coyle J T, Robinson M B, Qureshi I A, Mellits E D, Quaskey S
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Pediatr Res. 1988 Apr;23(4):368-74. doi: 10.1203/00006450-198804000-00006.
Herein we examine the effects of sodium benzoate and sodium phenylacetate on feeding and central serotonin turnover in a child with citrullinemia and in an animal model of congenital hyperammonemia, the ornithine transcarbamylase-deficient sparse-fur (spf/y) mouse. In the child, when the benzoate/phenylacetate dosage was increased from 200 to 375 mg/kg/day each, feeding decreased. There was an accumulation of benzoate and phenylacetate in blood and cerebrospinal fluid as well as an increased concentration of 5-hydroxyindoleacetic acid, a neurochemical marker for serotonin turnover, in cerebrospinal fluid. In the mouse, sodium benzoate had a biphasic effect on both plasma ammonium levels and brain serotonin turnover. Two percent oral benzoate was associated with an increase in ammonium level, while a 3% dose led to a decrease in ammonium. There was a similar effect on serotonin turnover noted in both the hyperammonemic spf/y and control CD-1/y mice. Sodium phenylacetate did not have a consistent effect on serotonin turnover. The mechanism by which benzoate increases brain serotonin turnover appears to involve competition with tryptophan for albumin binding sites. This results in increased free tryptophan in serum and brain. We speculate that some of the clinical symptoms of benzoate intoxication may be a consequence of altered serotonin turnover in the brain. We suggest that drug levels be monitored during therapy.
在此，我们研究了苯甲酸钠和苯乙酸钠对一名瓜氨酸血症患儿以及先天性高氨血症动物模型——鸟氨酸转氨甲酰酶缺陷型稀毛（spf/y）小鼠的进食和中枢5-羟色胺代谢的影响。在患儿中，当苯甲酸盐/苯乙酸盐的剂量从每千克体重每天200毫克增加到375毫克时，进食量减少。血液和脑脊液中苯甲酸盐和苯乙酸盐蓄积，同时脑脊液中5-羟吲哚乙酸（一种5-羟色胺代谢的神经化学标志物）浓度升高。在小鼠中，苯甲酸钠对血浆铵水平和脑5-羟色胺代谢均有双相效应。口服2%的苯甲酸盐会使铵水平升高，而3%的剂量则导致铵水平降低。在高氨血症的spf/y小鼠和对照CD-1/y小鼠中，对5-羟色胺代谢均观察到类似效应。苯乙酸钠对5-羟色胺代谢没有一致的影响。苯甲酸盐增加脑5-羟色胺代谢的机制似乎涉及与色氨酸竞争白蛋白结合位点。这导致血清和脑中游离色氨酸增加。我们推测，苯甲酸盐中毒的一些临床症状可能是脑内5-羟色胺代谢改变的结果。我们建议在治疗期间监测药物水平。
