Foulkes E C
Toxicol Appl Pharmacol. 1983 Dec;71(3):445-50. doi: 10.1016/0041-008x(83)90033-9.
Administration of heavy metals or maleic acid induces a condition resembling the Fanconi syndrome. In the case of metals, an apparently uncompetitive inhibition of reabsorption of amino acids was observed 2 days or longer after injection into rabbits (E. C. Foulkes and S. Blanck, Toxicol. Appl. Pharmacol. 64, 103-107, 1982). Transport of aspartate is now shown to be similarly inhibited by maleic acid and cephaloridin. Because maleic acid, as well as p-chloromercuribenzoate (PCMB) and Cd (in presence of mercaptoethanol), exerts an apparent uncompetitive effect within minutes of injection, the inhibition cannot simply reflect characteristics of regenerating epithelium. At low doses, PCMB inhibits aspartate reabsorption without altering transport of certain neutral amino acids, calcium, or p-aminohippurate. The apparent uncompetitive inhibition of aspartate reabsorption therefore does not connote general cytotoxicity. Metals cause relatively specific effects, manifested by functional lesions at the brush border. The mechanism of the aminoaciduric action of maleic acid remains unclear but cannot, under present conditions, involve back leakage of amino acids into tubular urine.
重金属或马来酸的给药会引发一种类似范科尼综合征的病症。就金属而言，在给兔子注射后2天或更长时间观察到对氨基酸重吸收的明显非竞争性抑制（E.C.福克斯和S.布兰克，《毒理学与应用药理学》64卷，第103 - 107页，1982年）。现已表明，马来酸和头孢菌素对天冬氨酸转运的抑制作用类似。由于马来酸以及对氯汞苯甲酸（PCMB）和镉（在存在巯基乙醇的情况下）在注射后几分钟内就产生明显的非竞争性作用，这种抑制不能简单地反映再生上皮的特性。在低剂量时，PCMB抑制天冬氨酸重吸收而不改变某些中性氨基酸、钙或对氨基马尿酸的转运。因此，天冬氨酸重吸收的明显非竞争性抑制并不意味着普遍的细胞毒性。金属会产生相对特异的作用，表现为刷状缘的功能性损伤。马来酸导致氨基酸尿的作用机制尚不清楚，但在目前情况下，不可能涉及氨基酸回漏到肾小管尿液中。
