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首页> 外文期刊>The Journal of toxicological sciences >Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats.
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Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats.

机译：反复口服甲氨蝶呤在大鼠中诱发高色微细胞贫血。

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Anaemia is a significant prognostic factor in cancer patients receiving anticancer drugs such as methotrexate (MTX). This study focuses on the effects of toxicological changes on the hematopoietic systems in male and female Wistar Hannover rats when MTX is orally administered at a dose of 0, 0.05, 0.15, or 0.45 mg/(kg·day) for a period of 28 days. Both male and female rats receiving 0.45 mg/kg MTX showed a decrease in the haemoglobin concentration (Hb), haematocrit, and erythrocyte count. Female rats showed a decrease in mean corpuscular volume (MCV) and an increase in cell mean Hb (CHCM) in total erythrocytes, including the mature erythrocytes. These results indicate that MTX causes the production of small, mature erythrocytes that contain a high concentration of Hb. MTX reduced the number of peripheral reticulocytes but produced the cells with a large size and a high concentration of Hb, as demonstrated by the reticulocyte MCV and CHCM as well as the content of haemoglobin per reticulocyte (CHr). Consistent with these findings, bone marrow haematopoiesis was impaired by MTX, as there was a reduction in erythroid count in rats of both sexes. The number of cells of the myeloid lineage reduced in female rats, followed by a reduction in the total leukocyte and neutrophil counts in peripheral blood. Thrombocytopenia was detected in a small population of rats. These results indicate that MTX induces hyperchromic microcytic anaemia and pancytopenia, and the use of MCV and CHCM in mature erythrocytes and reticulocytes, along with the CHr, gives a better understanding of the development and nature of anaemia.
机译：贫血是接受抗癌药物如甲氨蝶呤（MTX）的癌症患者的重要预后因素。这项研究的重点是口服，口服0、0.05、0.15或0.45 mg /（kg·天）MTX时，雄性和雌性Wistar Hannover雄性大鼠的毒理学变化对造血系统的影响。接受0.45 mg / kg MTX的雄性和雌性大鼠均显示血红蛋白浓度（Hb），血细胞比容和红细胞计数降低。雌性大鼠在包括成熟红细胞在内的总红细胞中显示平均红细胞体积（MCV）减少和细胞平均Hb（CHCM）增加。这些结果表明，MTX会导致含有高浓度Hb的成熟小红细胞的产生。如网状细胞MCV和CHCM以及每个网状细胞（CHr）的血红蛋白含量所证实的，MTX减少了外周网状细胞的数目，但是产生了具有大尺寸和高浓度Hb的细胞。与这些发现一致的是，MTX会削弱骨髓造血功能，因为这两种性别的大鼠的类红细胞数量都有所减少。在雌性大鼠中，髓系谱系的细胞数量减少，随后外周血中的白细胞和中性粒细胞总数减少。在少数大鼠中检测到血小板减少症。这些结果表明，MTX会诱发高色性小细胞性贫血和全血细胞减少症，在成熟的红细胞和网状细胞中，MCV和CHCM以及CHr的使用可以更好地了解贫血的发生和性质。

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