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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Hematological effects in F344 rats and B6C3F1 mice during the 13-week gavage toxicity study of methylene blue trihydrate.
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Hematological effects in F344 rats and B6C3F1 mice during the 13-week gavage toxicity study of methylene blue trihydrate.

机译：亚甲基蓝三水合物的13周管饲毒性研究中，对F344大鼠和B6C3F1小鼠的血液学影响。

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摘要

Methylene blue trihydrate is used widely as a dye and therapeutic agent. Methylene blue was administered by gavage to 30 animals/sex/dose group in a 0.5% aqueous methylcellulose suspension at doses of 0, 25, 50, 100, and 200 mg/kg. Blood samples from 10 animals/sex/dose group were collected at the end of study weeks 1, 6, and 13. Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. Splenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. There was a dose-related increase in absolute and relative spleen weight for both species. Microscopic examination revealed increased splenic hematopoiesis in all mice treatment groups and in rats at the 50 mg/kg dose level and above. Splenic congestion and bone marrow hyperplasia were also observed in these rat-dose groups. Mice at the higher doses showed hematopoiesis in the liver and accumulation of hemosiderin in Kupffer cells. These gross and microscopic findings are consistent with the development of hemolytic anemia. A dose-related increase in the reticulocyte count during study weeks 6 and 13 suggested a compensatory response to anemia.
机译：亚甲蓝三水合物被广泛用作染料和治疗剂。通过管饲法将亚甲基蓝以0.5、25、50、100和200 mg / kg的剂量灌胃于0.5％甲基纤维素水溶液中的30个动物/性别/剂量组。在研究的第1、6和13周结束时，收集了10种动物/性别/剂量组的血样。亚甲蓝处理导致高铁血红蛋白形成和对红细胞的氧化损伤，从而导致再生性贫血和多种组织继发于红细胞损伤的生化变化。早期的变化是高铁血红蛋白的剂量相关增加，其中大鼠和小鼠的反应幅度相似。小鼠似乎比大鼠对亨氏小体的形成和贫血的发展更敏感，贫血的发展以血红蛋白，血细胞比容和红细胞计数的减少为特征。尸检时，脾肿大在所有治疗的小鼠中以及在100 mg / kg（仅雄性）和200 mg / kg的大鼠中都明显。两种物种的绝对和相对脾脏重量都有剂量相关的增加。显微镜检查显示，在50 mg / kg或更高剂量水平的所有小鼠治疗组和大鼠中，脾造血功能均增加。在这些大鼠剂量组中还观察到脾脏充血和骨髓增生。较高剂量的小鼠在肝脏中表现出造血作用，在库普弗细胞中积累了铁血黄素。这些明显的和微观的发现与溶血性贫血的发生是一致的。在研究的第6周和第13周，网织红细胞计数与剂量有关，提示对贫血有补偿性反应。

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