Genotoxic and chemopreventive potentials of ethanol leaves extract of Annona muricata on N-Ethyl-N-Nitrosourea-induced pro-leukaemia carcinogen in mice model by bone marrow micronucleus assay

Oluwaseyi Bamisaye, A. Fashina, F. Abdulraheem, O. Akanni, Fadiora S. Olufemi
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Abstract

Background. Studies have proven the effect of several agents, including natural products, to induce, prevent and treat genotoxicity through experimental models and clinical trials. In this study, the genotoxic preventive potential of Annona muricata ethanol extract on N-Ethyl-N-Nitrosourea (ENU)-induced pro-leukaemia in mice models using micronuclei formation in bone marrow was assessed. Materials and methods. Forty-eight mice weighing 18-24g were randomly divided into six groups of eight mice. The mice were intravenously administered 20mg/kg of NEU 48 hourly 3 times, 80mg/kg of NEU 48 hourly 3 times. The negative control was fed with feed and water only. We introduced 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to NEU low dosage administration, 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to ENU high dosage and Annona muricata (ethanolic extract) administration, and gave commercial diet to the adverse/ toxicity group.  The bone marrow was harvested, smeared and stained using MayGrumwald. The procedure enabled the determination of micronucleus polychromatic erythrocytes (MNPCEs) microscopically. Results. Groups exposed to various dosages of the ENU yielded significantly increased MNPCEs, with group B producing higher MNPCEs. The groups treated with the extract displayed a significant reduction in the MNPCEs despite prior exposure to concentrations of NEU. The adverse group displayed no difference in MNPCEs compared with the negative control. Conclusion. The ENU induced genotoxicity depending on its concentration. The extract displayed a profound capacity to prevent genotoxicity and alleviate leukaemia with good tolerance.
用骨髓微核试验研究了小檗叶乙醇提取物对n -乙基- n -亚硝基源诱导的白血病前致癌物的遗传毒性和化学预防作用
背景。研究已经通过实验模型和临床试验证明了几种药物,包括天然产物,在诱导、预防和治疗遗传毒性方面的作用。在本研究中,通过在骨髓中形成微核,评估了番麻乙醇提取物对n -乙基- n -亚硝基脲(ENU)诱导的小鼠前白血病模型的遗传毒性预防潜力。材料和方法。48只体重18-24g的小鼠随机分为6组,每组8只。小鼠静脉注射NEU 20mg/kg 48小时3次,NEU 80mg/kg 48小时3次。阴性对照只饲喂饲料和水。在NEU低剂量给药前3周分别引入0.2ml (0.1g/ml)番麻醇提物,在ENU高剂量和番麻醇提物给药前3周分别引入0.2ml (0.1g/ml)番麻醇提物,并给予不良/毒性组商业饲粮。采集骨髓,用MayGrumwald涂片染色。该方法可在显微镜下测定微核多染红细胞(mnpce)。暴露于不同剂量ENU的组mnpce显著增加,其中B组mnpce更高。尽管先前暴露于NEU浓度,但用提取物处理的组mnpce显着降低。不良组mnpce与阴性对照组比较差异无统计学意义。ENU的遗传毒性取决于其浓度。提取物显示出深刻的能力,以防止遗传毒性和减轻白血病良好的耐受性。
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