Toxicological implications of sequential administration of herbal and conventional medicines: Evidence from an in vivo study on Azadirachta indica and artesunate in male Wistar rats

G. Forcados, VO Adamu, MT Abdulsalam, N. Aminu, TM Anjuwon, M. Otor, JR Riki, A. Muhammad
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Abstract

In most parts of West Africa and other developing countries, herbal medicines are sometimes used by patients concomitantly receiving conventional drugs, which can result in potentially serious adverse effects. This study examined in vivo cytotoxic effects of Azadirachta indica extracts followed by artesunate administration on some markers of liver and kidney toxicity. Serum ALT, GGT, urea, creatinine, interleukin 1β, tumor necrosis factor α, tissue malondialdehyde and glutathione levels and liver and kidney histology in healthy male Wistar rats administered 100 and 200 mg/kg A. indica for 5 days followed by 10 mg/kg Artesunate for 5 days was determined. Results showed significantly (p < 0.05) higher serum ALT, GGT, urea, creatinine, interleukin 1β and tumor necrosis factor α levels with proportional increase of 16.5, 21.7, 9.2, 6.9, 9.1 and 9.1% respectively when compared to normal control was observed. Malondialdehyde levels were significantly (p < 0.05) higher with a proportional increase of 57.8%, while glutathione levels were significantly (p < 0.05) lower with a proportional decrease of 13.4% in liver homogenates of the treated rats relative to normal control. Histological examination of the liver and kidney of the co-treated rats showed vascular congestion and necrosis. Collectively, the results suggest that administration of A. indica followed by artesunate could predispose to liver and kidney associated cytotoxicity. These findings could have implications for people who habitually use herbal preparations and conventional drugs in sequential fashion.
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中草药和常规药物顺序给药的毒理学意义:来自雄性Wistar大鼠体内印楝和青蒿琥酯研究的证据
在西非大部分地区和其他发展中国家,患者有时在服用常规药物的同时使用草药,这可能导致潜在的严重不良反应。本研究考察了印楝提取物在给予青蒿琥酯后对一些肝脏和肾脏毒性标志物的体内细胞毒性作用。测定健康雄性Wistar大鼠血清ALT、GGT、尿素、肌酐、白细胞介素1β、肿瘤坏死因子α、组织丙二醛和谷胱甘肽水平及肝、肾组织组织学变化,分别给药100和200 mg/kg A. indica,再给药10 mg/kg青蒿素5 d。结果显示,与正常对照组相比,血清ALT、GGT、尿素、肌酐、白细胞介素1β和肿瘤坏死因子α水平显著(p < 0.05)升高,分别成比例升高16.5%、21.7、9.2、6.9、9.1和9.1%。各组大鼠肝脏匀浆中丙二醛水平显著(p < 0.05)升高,比例升高57.8%;谷胱甘肽水平显著(p < 0.05)降低,比例降低13.4%。联合治疗大鼠肝、肾组织学检查显示血管充血、坏死。综上所述,研究结果表明,在给药后服用青蒿琥酯可导致肝脏和肾脏相关的细胞毒性。这些发现可能对那些习惯性地连续使用草药制剂和常规药物的人产生影响。
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