Chandra A M, Qualls C W, Reddy G, Meinkoth J H
Department of Veterinary Pathology, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078, USA.
J Toxicol Environ Health. 1995 Sep;46(1):57-72. doi: 10.1080/15287399509532018.
We studied the hematological effects of single and repeated exposure to 1,3,5-trinitrobenzene (TNB) in rats. Male F-344 rats were gavaged with TNB at 35.5 and 71 mg/kg in corn oil. Blood was collected 5 h and 24 h after a single oral dose or 24 h after daily oral doses for 4 or 10 d in four different set of experiments. A dose-dependent methemoglobinemia was present only in blood collected 5 h after a single dose. A highly significant dose-dependent anemia with reduced red cells, hemoglobin, and hemotocrit was present in rats receiving TNB for 4 or 10 d. A dose-dependent decrease in serum triglycerides was present in rats receiving TNB for 10 d. There was no hemolysis when rat erythrocytes were incubated with TNB (in vitro) for 9 h. Spectral changes of hemoglobin recorded during the incubation with TNB confirm methemoglobin formation and progressive denaturation of hemoglobin-forming hemichromes. The significance of methemoglobin and hemichrome formation is discussed, and a probable hypothesis for the hemolytic anemia is suggested.
我们研究了大鼠单次及重复接触1,3,5-三硝基苯(TNB)后的血液学效应。将雄性F-344大鼠用玉米油配制成的35.5和71 mg/kg的TNB溶液灌胃。在四组不同的实验中,单次口服给药后5小时和24小时或每日口服给药4天或10天后24小时采集血液。仅在单次给药后5小时采集的血液中出现了剂量依赖性高铁血红蛋白血症。在接受TNB处理4天或10天的大鼠中出现了高度显著的剂量依赖性贫血,红细胞、血红蛋白和血细胞比容降低。在接受TNB处理10天的大鼠中,血清甘油三酯出现剂量依赖性降低。当大鼠红细胞与TNB在体外孵育9小时时未发生溶血。在与TNB孵育期间记录的血红蛋白光谱变化证实了高铁血红蛋白的形成以及形成半色素的血红蛋白的渐进性变性。讨论了高铁血红蛋白和半色素形成的意义,并提出了溶血性贫血的一个可能假说。