亚硒酸钠对大鼠溴苯毒性的影响。II. 代谢

Effect of sodium selenite upon bromobenzene toxicity in rats. II. Metabolism.

作者信息

Merrick B A, Davies M H, Schnell R C

出版信息

Toxicol Appl Pharmacol. 1986 Apr;83(2):279-86. doi: 10.1016/0041-008x(86)90305-4.

Abstract

The effects of sodium selenite (12.5 or 30 mumol/kg, ip) upon bromobenzene metabolism were examined in male rats treated with selenite at 72 hr prior to bromobenzene exposure (7.5 mmol/kg, ip). The inhibitory nature of selenium treatment upon xenobiotic metabolism and increased production of hepatic thiol suggested that selenite might affect metabolic activation and detoxification of bromobenzene. Selenite treatment lowered in vivo covalent binding of [14C]bromobenzene while the in vitro covalent binding of [14C]bromobenzene in microsomes isolated from selenite-treated rats was unaffected compared to control. When the rate of [14C]bromobenzene decline in whole blood was evaluated in selenite-treated rats over 48 hr after bromobenzene administration, no significant differences were observed when compared to control. Furthermore, values of glutathione conjugates and hydroxylated metabolites of bromobenzene were similar in urine samples collected over 48 hr from selenite and control rats. Mechanistically, reduction of bromobenzene hepatotoxicity by selenite is not mediated through an altered metabolism of bromobenzene, but by alteration of cellular events occurring after metabolic activation.

摘要

在给雄性大鼠腹腔注射溴苯（7.5 mmol/kg）前72小时，腹腔注射亚硒酸钠（12.5或30 μmol/kg），研究其对溴苯代谢的影响。硒处理对异源物质代谢的抑制作用以及肝脏硫醇生成的增加表明，亚硒酸钠可能会影响溴苯的代谢活化和解毒。亚硒酸钠处理降低了[14C]溴苯的体内共价结合，而与对照组相比，从亚硒酸钠处理的大鼠分离的微粒体中[14C]溴苯的体外共价结合未受影响。在给溴苯后48小时内评估亚硒酸钠处理大鼠全血中[14C]溴苯的下降速率，与对照组相比未观察到显著差异。此外，在亚硒酸钠处理组和对照组大鼠48小时内收集的尿液样本中，溴苯的谷胱甘肽结合物和羟基化代谢物的值相似。从机制上讲，亚硒酸钠降低溴苯肝毒性不是通过改变溴苯的代谢，而是通过改变代谢活化后发生的细胞事件来实现的。