Saljooghi Amir Shokooh, Babaie Maryam, Mendi Fatemeh Delavar, Zahmati Maliheh, Saljooghi Zoheir Shokouh
Department of Chemistry, Ferdowsi University of Mashhad, Mashhad, Islamic Republic of Iran.
Department of Fisheries, Chabahar Maritime University, Chabahar, Islamic Republic of Iran
Toxicol Ind Health. 2016 Jan;32(1):83-8. doi: 10.1177/0748233713498442. Epub 2013 Sep 10.
The hypothesis that two known chelators deferasirox (4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing thallium from the body was tested in a new acute rat model. 7-week-old male Wistar rats received chelators: deferasirox (orally), DFO (intraperitoneal; i.p.), or deferasirox + DFO as 75 or 150 mg/kg dose half an hour after a single i.p. administration of 8 mg thallium/kg body weight in the form of chloride. Serum thallium concentration, urinary thallium, and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level, while DFO was more effective than deferasirox in enhancing urinary thallium excretion, deferasirox was more effective than DFO in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the DFO effect on thallium and DFO did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of thallium chelators. Urinary values were more useful because of the high variability of serum results.
在一种新的急性大鼠模型中，对两种已知的螯合剂地拉罗司（4-[3,5-双(2-羟苯基)-1,2,4-三唑-1-基]-苯甲酸）和去铁胺（DFO）联合治疗在从体内清除铊方面可能比单一疗法更有效的假设进行了测试。7周龄雄性Wistar大鼠在以氯化物形式腹腔注射8 mg铊/千克体重半小时后，接受螯合剂治疗：地拉罗司（口服）、DFO（腹腔注射；i.p.），或地拉罗司+DFO，剂量为75或150 mg/kg。通过石墨炉原子吸收光谱法测定血清铊浓度、尿铊和铁排泄量。两种螯合剂仅在较高剂量水平有效，而DFO在促进尿铊排泄方面比地拉罗司更有效，地拉罗司在促进尿铁排泄方面比DFO更有效。在联合治疗组中，地拉罗司未增加DFO对铊的作用，DFO也未增加地拉罗司对铁清除的作用。我们的结果支持了这种动物模型在铊螯合剂体内初步测试中的实用性。由于血清结果的高变异性，尿值更有用。
