Monks T J, Lau S S
Life Sci. 1984 Jul 30;35(5):561-8. doi: 10.1016/0024-3205(84)90250-9.
Bromobenzene causes hepatic and extrahepatic toxicity in rats. Toxicity is related to the presence of covalently bound material in these tissues. A major bromobenzene metabolite, p-bromophenol, has been shown to give rise to covalently bound material in liver, lung and kidney in vivo, but is not toxic. p-Bromophenol is formed from bromobenzene in liver, lung and kidney microsomes and is subsequently metabolized to 4-bromocatechol and covalently bound material. Bromobenzene-3,4-oxide generated in situ by liver microsomes, is detoxified by kidney, liver and lung cytosol. The results suggest that the kidney toxicity caused by bromobenzene is probably not mediated by either bromobenzene-3,4-oxide or the reactive metabolites of p-bromophenol. In contrast, bromobenzene-3, 4-oxide may play a role in the lung toxicity observed after bromobenzene administration. However, the covalently bound material found in extrahepatic tissues may be derived from both bromobenzene-3,4-oxide or the reactive metabolites of p-bromophenol, which may be formed directly by these tissues or transported there from the liver.
溴苯可导致大鼠肝脏和肝外组织中毒。毒性与这些组织中存在的共价结合物质有关。一种主要的溴苯代谢产物对溴苯酚，已被证明在体内可在肝脏、肺和肾脏中产生共价结合物质，但无毒。对溴苯酚在肝脏、肺和肾脏微粒体中由溴苯形成，随后代谢为4-溴邻苯二酚和共价结合物质。肝脏微粒体原位生成的溴苯-3,4-氧化物可被肾脏、肝脏和肺的胞液解毒。结果表明，溴苯引起的肾脏毒性可能不是由溴苯-3,4-氧化物或对溴苯酚的活性代谢产物介导的。相比之下，溴苯-3,4-氧化物可能在溴苯给药后观察到的肺毒性中起作用。然而，在肝外组织中发现的共价结合物质可能来自溴苯-3,4-氧化物或对溴苯酚的活性代谢产物，这些物质可能由这些组织直接形成或从肝脏转运至此处。
