The protective role of Ageratum conyzoides (Billy goat weed) in cyclophosphamide induced haematological damage and cytogenotoxicity

A. Mobolaji, T. Barde, F. O. Oyelowo-Abdulraheem, I. Usende
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Abstract

Medical plants are now explored as alternative for treatment and prevention of various disease conditions. Ageratum conyzoides (A. conyzoides) is a common plant with long traditional medicinal use history. This study investigated the hypothesis that A. conyzoides protects against haematological damage and cytogenotoxicity induced by acute exposure to cyclophosphamide. A total of twenty (24) adult male Wistar rats weighing 208.50±28.3 g was randomly divided into four groups of six animals each. Group 1 served as control group and received 0.5 ml of Tween-20 orally and sterile injection water intraperitoneally on days 1 and 4. Group 2 received 0.5ml of Tween-20 orally and 40 mg/kg body weight of cyclophosphamide intraperitoneally on days 1 and 4. Group 3 received 500 mg/kg body weight of A. conyzoides extract orally and sterile injection water intraperitoneally on days 1 and 4. Group 4 received 500 mg/kg body weight of A. conyzoides extract orally and 40 mg/kg body weight of cyclophosphamide intraperitoneally on days 1 and 4. Oral treatment was daily and lasted for 7 days. Whole blood was collected for complete blood count and assessment of Neutrophil-to-Lymphocyte ratio, Monocytes-to-Lymphocytes ratio (MLR) and Platelet-to-Lymphocyte Ratio (PLR) as biomarkers of systemic inflammation and immunosuppression; and bone marrow smear were analyzed for micronucleated normochromated and polychromated erythrocytes (MNNCE and MNPCE), and PCE/NCE ratio was scored as index of cytotoxicity following exposure to cycophosphamide and the protective role of A. conyzoides. Our results showed cyclophosphamide caused significant reduction in WBC, platelet, RBC, Hb and PCV values. Also, cyclophosphamide induced significant increased abnormal RBC morphophenotypes, including irregular, teardrop, macrocytes, helmet, fragmented, sickle, burr and target cells, with consequent increase in frequencies of micronucleated polychromatic and micronucleated normochromatic erythrocytes. Interestingly, treatment with A. conyzoides produced a significant amelioration of these cyclophosphamide-mediated effects. The mechanisms by which A. conyzoides ameliorated these toxic effects of cyclophosphamide remain to be fully investigated.
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山羊草对环磷酰胺致血液学损伤和细胞遗传毒性的保护作用
药用植物现在被探索作为治疗和预防各种疾病的替代方法。鹰嘴豆(Ageratum conyzoides)是一种具有悠久传统药用历史的常见植物。本研究探讨了一种假说,即圆锥虫对急性环磷酰胺暴露引起的血液学损伤和细胞遗传毒性具有保护作用。选取体重208.50±28.3 g的成年雄性Wistar大鼠20(24)只,随机分为4组,每组6只。第1组为对照组,于第1、4天口服Tween-20 0.5 ml,腹腔注射无菌水。2组大鼠于第1、4天口服Tween-20 0.5ml,腹腔注射环磷酰胺40 mg/kg体重。第3组大鼠于第1、4天口服500 mg/kg体重的刺梨提取物,并腹腔注射无菌注射水。第4组在第1和第4天分别口服500 mg/kg体重的刺梨提取物和40 mg/kg体重的环磷酰胺。每日口服治疗,疗程7 d。采集全血进行全血计数,并评估中性粒细胞与淋巴细胞比值、单核细胞与淋巴细胞比值(MLR)和血小板与淋巴细胞比值(PLR)作为全系统炎症和免疫抑制的生物标志物;分析骨髓涂片中微核正铬化红细胞和多铬化红细胞(MNNCE和MNPCE),并以PCE/NCE比值作为环磷酰胺暴露后的细胞毒性指标和棘球蚴的保护作用。我们的结果显示,环磷酰胺引起WBC、血小板、RBC、Hb和PCV值显著降低。此外,环磷酰胺诱导异常红细胞形态表型显著增加,包括不规则、泪滴、巨细胞、头盔、碎片化、镰状、毛刺和靶细胞,因此微核多染红细胞和微核正染红细胞的频率增加。有趣的是,conyzoides治疗显著改善了这些环磷酰胺介导的效应。其改善环磷酰胺毒性作用的机制还有待进一步研究。
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