Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, BP no. 17, F-92262 Fontenay-aux-Roses Cedex, France.
Environ Toxicol Pharmacol. 2009 Nov;28(3):363-9. doi: 10.1016/j.etap.2009.06.004. Epub 2009 Jun 24.
The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment.
铀在民用和军事应用中的广泛使用增加了人类慢性暴露的风险。铀是一种具有轻微放射性的重金属，主要具有化学毒性，特别是在肾脏中，但也在肝脏中。以前的少数研究表明，铀对细胞色素 P450 同工酶（XME）有一些影响，可能会干扰药物的药代动力学。本研究的目的是确定慢性（9 个月）非肾毒性低剂量贫铀（DU，1mg/大鼠/天）暴露是否会改变肝脏 XME，使用单次非肝毒性对乙酰氨基酚（APAP）治疗（50mg/kg）。在用 APAP 处理后，大多数分析的 XME 在基因表达水平上被诱导，但在 DU 暴露的大鼠中，只有 CYP3A2 在 APAP 处理后 3 小时显著增加，而在未暴露的大鼠中仍保持在基础水平。总之，这些结果表明，慢性非肾毒性 DU 暴露特别是在单次治疗性 APAP 治疗后特别改变 CYP3A2。
