重复砷化镓暴露后生化和免疫毒性的改变及其在大鼠体内通过施用间-2,3-二巯基丁二酸和 2,3-二巯基丙磺酸钠的恢复。

Biochemical and immunotoxicological alterations following repeated gallium arsenide exposure and their recoveries by meso-2,3-dimercaptosuccinic acid and 2,3-dimercaptopropane 1-sulfonate administration in rats.

机构信息

Division of Pharmacology and Toxicology, Gwalior, India.

出版信息

Environ Toxicol Pharmacol. 1996 Dec 20;2(4):315-20. doi: 10.1016/s1382-6689(96)00063-4.

Abstract

Efficacy of two analogues of British anti-lewisite (BAL), meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-suffonate (DMPS), in depleting arsenic and gallium concentration of blood and other soft tissues, in restoring altered blood, liver and renal biochemical variables and some immunlogical indices were investigated in male rats exposed to multiple doses of gallium arsenide (GaAs). The results indicate that exposure to gallium arsenide produced a significant inhibition of blood δ-aminolevulinic acid dehydratase (ALAD) activity, an increase in urinary ALA excretion and blood zinc protoporphyrin level. Blood glutathione (GSH) contents also decreased on GaAs exposure. No influence of GaAs however, on serum transminase activity or hepatic GSH contents was noticed, although, renal alkaline phosphatase activity decreased significantly on GaAs exposure. Further, a marked influence of GaAs administration on immunological variables like relative thymus and spleen weight, spleen cellularity, antibody forming cell (AFC) response to sheep RBC and delayed type of hypersensitivity (DTH) was observed. These data indicate that multiple exposure to GaAs may produce an adverse effect on the haematopoietic, renal and immune system. Further, post exposure treatment with two thiols, meso-2,3-dimercaptosuccinic acid and sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), DMPS proved more effective than DMSA in producing an effective reversal of altered immunological variables and reducing arsenic concentration of spleen, liver, kidney and blood. Biochemical variables, on the other hand, responded less favorably to the treatment of DMSA or DMPS except for a significant recovery in the activity of blood δ-aminolevulinic acid dehydratase (ALAD) following DMSA administration. The results suggest that DMPS could be an effective chelating drug for reversing most of the GaAs induced immunological alterations and reducing tissue arsenic burden.

摘要

两种双巯丁二酸（DMSA）和 2,3-二巯基丙烷-1-磺酸（DMPS）类似物对英国抗路易斯气（BAL）的疗效，用于降低血砷和镓浓度以及恢复血液、肝脏和肾脏生化变量以及一些免疫指标的改变，在雄性大鼠暴露于砷化镓（GaAs）的多剂量下进行了研究。结果表明，暴露于砷化镓会显著抑制血液 δ-氨基酮戊酸脱水酶（ALAD）的活性，增加尿中 ALA 的排泄和血液锌原卟啉水平。血液谷胱甘肽（GSH）含量也随 GaAs 暴露而降低。然而，GaAs 对血清转氨酶活性或肝 GSH 含量没有影响，尽管 GaAs 暴露后肾碱性磷酸酶活性显著降低。此外，GaAs 给药对免疫变量如相对胸腺和脾脏重量、脾脏细胞数、对绵羊 RBC 的抗体形成细胞（AFC）反应和迟发型超敏反应（DTH）有明显的影响。这些数据表明，多次暴露于 GaAs 可能会对造血、肾脏和免疫系统产生不良影响。此外，用两种硫醇（meso-2,3-二巯丁二酸和 2,3-二巯基丙烷-1-磺酸钠（DMPS））进行暴露后治疗，DMPS 比 DMSA 更有效地逆转改变的免疫变量，并降低脾脏、肝脏、肾脏和血液中的砷浓度。另一方面，除了 DMSA 给药后血液 δ-氨基酮戊酸脱水酶（ALAD）的活性显著恢复外，生化变量对 DMSA 或 DMPS 的治疗反应较差。结果表明，DMPS 可能是一种有效的螯合剂，可逆转大多数 GaAs 诱导的免疫改变，并降低组织砷负荷。