Bilgin Asli O, Mammadov Renad, Suleyman Bahadir, Unver Edhem, Ozcicek Fatih, Soyturk Mehmet, Cimen Ferda K, Kurt Nezahat, Suleyman Halis
Department of Pharmacology, Erzincan Binali Yildirim University, Erzincan, Turkey.
Department of Pulmonology, Erzincan Binali Yildirim University, Erzincan, Turkey.
An Acad Bras Cienc. 2020;92(1):e20190261. doi: 10.1590/0001-3765202020190261. Epub 2020 May 11.
Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.
阿糖胞苷有效地用于治疗成人急性白血病，但它有致命肺水肿这种剂量限制性副作用，因为它会增加肺泡毛细血管的血管通透性。本研究的目的是对芦丁对大鼠阿糖胞苷相关肺水肿的影响进行放射学、生物化学和组织病理学研究。通过以50毫克/千克的剂量口服芦丁，用芦丁+阿糖胞苷组合治疗大鼠；其他大鼠组口服相同体积的生理盐水。在给予芦丁或生理盐水1小时后，芦丁+阿糖胞苷组和阿糖胞苷组腹腔注射阿糖胞苷（200毫克/千克）。每天重复此给药程序，持续14天。放射学检查显示，单独给予阿糖胞苷的动物中有50%出现肺水肿，但芦丁+阿糖胞苷组未出现水肿。加入芦丁可减少肺组织中阿糖胞苷相关的丙二醛、肿瘤坏死因子-α和核因子-κB的量。芦丁还抑制一氧化氮导致的总谷胱甘肽的减少。这些发现表明，芦丁可能是一种有益的辅助药物，可将阿糖胞苷相关肺水肿的发生降至最低。
