Giglio M J, Frid A, Bozzini C E
Department of Pathology I, Faculty of Odontology, University of Buenos Aires, Argentina.
Int J Clin Lab Res. 1997;27(3):199-201. doi: 10.1007/BF02912458.
Uranium salts, such as uranyl nitrate, induce severe renal dysfunction and tubular necrosis and a significant impairment of both oxygen dependent erythropoietin production and response to recombinant human erythropoietin. All effects are transient and reach maximal severity on the 7th day post injection. We investigated the effects of ethane 1-hydroxy-1, 1-bisphosphonate, which counteracts the inhibitory effect of uranyl nitrate on bone formation, on the negative erythropoietic effects of uranyl nitrate. Adult female Wistar rats received 1 mg/kg body weight of uranyl acetate by the i.v. route. Ethane 1-hydroxy-1,1-bisphosphonate was injected simultaneously at a dose of 7.5 mg/kg by the same route. Seven days after drug injections, plasma erythropoietin was estimated after hypobaric hypoxemia or cobalt chloride administration. The response to exogenous erythropoietin was also measured in uranyl nitrate- and/or ethane 1-hydroxy-1,1-bisphosphonate-injected rats made polycythemic by transfusion. The erythroid response was quantitated in terms of red blood cell 59iron uptake. Ethane 1-hydroxy-1, 1-bisphosphonate counteracted the effect of uranyl nitrate on oxygen-dependent and cobalt-dependent erythropoietin production, but did not correct the right shift of the dose-response relationship for exogenous erythropoietin induced by uranyl nitrate in the polycythemic rat.
铀盐，如硝酸铀酰，可导致严重的肾功能障碍和肾小管坏死，以及对氧依赖型促红细胞生成素的产生和对重组人促红细胞生成素的反应造成显著损害。所有这些影响都是短暂的，在注射后第7天达到最严重程度。我们研究了乙烷1-羟基-1,1-二膦酸盐（它可抵消硝酸铀酰对骨形成的抑制作用）对硝酸铀酰的负性促红细胞生成作用的影响。成年雌性Wistar大鼠通过静脉注射途径接受1mg/kg体重的醋酸铀酰。同时通过相同途径以7.5mg/kg的剂量注射乙烷1-羟基-1,1-二膦酸盐。药物注射7天后，在低压低氧血症或给予氯化钴后测定血浆促红细胞生成素。还在通过输血造成红细胞增多的注射硝酸铀酰和/或乙烷1-羟基-1,1-二膦酸盐的大鼠中测量对外源性促红细胞生成素的反应。根据红细胞对59铁的摄取来定量红细胞生成反应。乙烷1-羟基-1,1-二膦酸盐抵消了硝酸铀酰对氧依赖型和钴依赖型促红细胞生成素产生的影响，但并未纠正硝酸铀酰在红细胞增多大鼠中诱导的外源性促红细胞生成素剂量反应关系的右移。
