抗寄生虫和抗疟疾药物联合给药后Wistar大鼠的生化、组织病理学和诱变变化

A. A. Obiajunwa, Emmanuel Taiwo Idowu, O. Otubanjo
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摘要

目的:探讨抗疟药与花药联合用药对白化大鼠肝肾组织病理改变及生化调节的影响。研究地点和时间:本研究在尼日利亚拉各斯阿卡拉各斯大学动物学系进行。方法:选取13-15周龄雄性成年白化病大鼠20(25)只,随机分为5组,每组5只,每日分别口服吡喹酮(PZQ 50 mg/kg体重)和伊维菌素(IVM 0.4 mg/kg体重)、阿苯达唑(ALB 15 mg/kg体重)、蒿甲醚-甲氰菊酯(ACT 140 mg/kg体重)人体治疗剂量,对照组为蒸馏水1ml。在试验第8天和第15天采用组织病理学、生化和诱变指标研究这些处理的毒性作用。结果:生化评价显示,治疗组AST、ALT、ALP、钾均较对照组明显降低。治疗组钙、白蛋白和碳酸氢盐水平均升高。肝脏的组织病理学评估显示,门静脉区局灶性炎症的发生率普遍较高,但除单一PZQ治疗组以脂肪浸润为特征外,各组间未见严重程度差异。肾脏组织普遍出现系膜损伤和肾小球损伤。PZQ+ IVM单药组肾脏病变较重,而PZQ+ACT单药组肾脏病变较轻。在联合治疗中,特别是在PZQ+ IVR和PZQ+ ACT组,记录了高发生率的精子头异常所表明的致突变效应。结论:联合治疗具有协同作用,在人体治疗剂量下可引起肾毒性、抗利尿、脱水和致突变性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biochemical, Histopathological and Mutagenic Changes Following the Co-administration of Antihelminthic and Antimalarial Drugs in Wistar Rats
Aim: To determine the effects of antimalaria and antheminthic drugs combination in the incidence of histopathological alteration and biochemical modulations in liver and kidney of albino rats. Place and Duration of Study: The study was undertaken at the Zoology Department University of Lagos Akoka Lagos Nigeria. Methodology: A total of twenty (25) Male adult albino rats of 13-15 weeks old were divided into 5 groups of 5 rats each and daily oral administration of human therapeutic doses of praziquantel (PZQ 50 mg/kg body weight) separate and in combination with ivermectin (IVM 0.4 mg/kg body weight), albendazole (ALB 15 mg/kg body weight) and Artemether-lumefanthrine (ACT 140 mg/kg body weight) was administered with the  group which serve as the control receiving 1ml distilled water. Toxic effects due to these treatments were investigated using histopathological, biochemical and mutagenic indices at day 8th and 15th of the study. Results: Biochemical assessment revealed significant reduction in AST, ALT, ALP and potassium in the treatment group compared to the control. Increase in the level calcium, Albumin and bicarbonate were also observed in treatment groups. Histopathological assessment of the liver showed a general incidence of focal inflammation along the portal tract area, but did not show any differential severity across treatment groups except for single PZQ treatment group which were characterized by fatty infiltration. A general occurrence of mesangial damage and glomerula injury was observed in kidney tissues. Renal lesions were more severe in single PZQ + IVM treatment groups while mild lesions characterized renal tissue from PZQ+ACT treatment groups. Mutagenic effects as indicated by the high incidence of sperm head abnormalities was recorded across combination treatments especially in PZQ+ IVR and PZQ+ ACT groups. Conclusion: Findings suggest that combination therapies are synergistic and could result in nephrotoxicity, antidiuretic effects, dehydration and mutagenicity at human therapeutic doses.
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