Gómez M, Domingo J L, del Castillo D, Llobet J M, Corbella J
Laboratory of Toxicology and Biochemistry, School of Medicine, Rovira i Virgili University, San Lorenzo, Spain.
Hum Exp Toxicol. 1994 Feb;13(2):135-9. doi: 10.1177/096032719401300213.
The relative effectiveness of deferoxamine (DFO), 1,2-dimethyl-1,3-hydroxypyrid-4-one (L1), and citric and succinic acids in mobilizing and promoting excretion of aluminium (Al) were compared in female uraemic rats which had previously received aluminium nitrate nonahydrate i.p. in a daily dose of 45 mg kg-1 for 3 weeks (5 days/week). Chelators were administered s.c. at doses equal to one-eighth of their respective LD50 for five days. L1 was also given p.o. in doses of 200 mg kg-1 day-1. Total urines were collected 24 h after each chelator administration. Total urinary Al excreted over the 5-day period, expressed as mg kg-1, were: controls, 3.4; DFO-treated, 4.5 (P < 0.05); citric acid-treated, 3.7; and succinic acid-treated, 2.7. Although the daily amounts of Al excreted into urine by L1-treated rats were significantly higher (P < 0.001) than those of the controls, most animals died during the period of treatment. Measurements of Al in selected tissues 24 h after the last administration of each chelator revealed that none of the compounds significantly altered the Al concentration in bone, kidney, and brain, whereas only DFO and succinic acid significantly reduced the levels of Al in spleen. Moreover, L1 (given s.c. or p.o.) and citric acid treatment led to a significant reduction in the liver Al burden. These results indicate the need for further investigations to determine the toxicity and the therapeutical safety margins of L1.
在先前经腹腔注射给予每日剂量为45 mg/kg的九水硝酸铝，持续3周（每周5天）的雌性尿毒症大鼠中，比较了去铁胺（DFO）、1,2 - 二甲基 - 1,3 - 羟基吡啶 - 4 - 酮（L1）以及柠檬酸和琥珀酸在动员和促进铝（Al）排泄方面的相对有效性。螯合剂按各自半数致死剂量的八分之一皮下注射，持续5天。L1也以200 mg/kg/天的剂量口服给药。每次给予螯合剂24小时后收集总尿液。5天期间以mg/kg表示的总尿铝排泄量分别为：对照组3.4；DFO处理组4.5（P < 0.05）；柠檬酸处理组3.7；琥珀酸处理组2.7。虽然L1处理组大鼠每日尿铝排泄量显著高于对照组（P < 0.001），但大多数动物在治疗期间死亡。在最后一次给予每种螯合剂24小时后，对选定组织中的铝进行测量，结果显示，这些化合物均未显著改变骨、肾和脑中的铝浓度，而只有DFO和琥珀酸显著降低了脾脏中的铝水平。此外，L1（皮下或口服给药）和柠檬酸处理导致肝脏铝负荷显著降低。这些结果表明需要进一步研究以确定L1的毒性和治疗安全范围。
