Flora S J, Mathur S, Mathur R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Toxicology. 1995 Jan 6;95(1-3):167-75. doi: 10.1016/0300-483x(94)02903-8.
The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution, hepatic and hematopoietic toxicity of beryllium were compared in male rats exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg, orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg marginally elevated the fecal excretion of beryllium. DMPS was effective in depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg) results in the redistribution of beryllium to blood. Beryllium-induced inhibition of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase) were restored considerably with the chelating agents. Also, hepatic and renal histopathological lesions were less marked in rats treated with DMPS (50 mg/kg) compared with those treated with beryllium per se and DMSA. These effects were more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These results suggest that treatment with DMPS has some beneficial effects in experimental beryllium intoxication.
在暴露于铍的雄性大鼠中，比较了两种螯合剂，即内消旋-2,3-二巯基琥珀酸（DMSA）和2,3-二巯基丙烷-1-磺酸盐（DMPS）对铍的动员、分布、肝脏和造血毒性的影响。动物每周5天、每天口服硝酸铍（0.5mg/kg），持续21天。在最后一剂后的24小时，它们被注射一种螯合剂（DMSA或DMPS）（25或50mg/kg，每天两次，共5天）。以50mg/kg的剂量施用DMSA和DMPS会使铍的粪便排泄量略有增加。DMPS能有效降低肝脏、脾脏和肾脏中的铍含量。然而，DMPS（50mg/kg）会导致铍重新分布到血液中。铍诱导的肝脏碱性磷酸酶和肝脏三磷酸腺苷酶（ATPase）的抑制作用通过螯合剂得到了相当程度的恢复。此外，与单独用铍和DMSA处理的大鼠相比，用DMPS（50mg/kg）处理的大鼠的肝脏和肾脏组织病理学损伤不那么明显。这些作用在50mg/kg剂量的螯合剂下比在25mg/kg时更显著。这些结果表明，用DMPS治疗对实验性铍中毒有一些有益的作用。
