Raji J I, Onwuamah C K, Odeigah P G C
Department of Cell Biology and Genetics, University of Lagos, Nigeria.
Centre for Human Virology and Genomics, Nigerian Institute of Medical Research, Lagos, Nigeria.
J Toxicol. 2018 Aug 23;2018:4671326. doi: 10.1155/2018/4671326. eCollection 2018.
Artemisinin-based combination therapy is used to treat uncomplicated malaria disease in most endemic countries. Although most antimalarial drugs are effective in killing the parasite, there is a concern of induced toxicity to the cell. Here, the cytogenotoxicity of dihydroartemisinin-piperaquine phosphate (DHAP), a coformulation for artemisinin-based combination therapy, was evaluated using model. The toxicity on the mitotic index varies with the duration of exposure and dose tested. Chromosome aberrations observed include chromosome fragments, chromosome bridges, binucleated cells, and micronucleated cells. This study showed that DHAP can depress mitosis and induce chromosome abnormalities. Their accumulation in cells may be inhibitory to cell division and growth. This calls for caution in the administration of artemisinin combination therapy for the treatment of malaria ailment. Wide spacing of dosage is therefore suggested in order to avoid the risk of genetic damage.
在大多数疟疾流行国家,基于青蒿素的联合疗法被用于治疗非复杂性疟疾。尽管大多数抗疟药物能有效杀死疟原虫,但人们担心其会对细胞产生诱导毒性。在此,使用模型评估了基于青蒿素的联合疗法的复方制剂磷酸二氢青蒿素-哌喹(DHAP)的细胞遗传毒性。对有丝分裂指数的毒性随暴露时间和测试剂量而变化。观察到的染色体畸变包括染色体片段、染色体桥、双核细胞和微核细胞。这项研究表明,DHAP可抑制有丝分裂并诱导染色体异常。它们在细胞中的积累可能会抑制细胞分裂和生长。这就要求在使用青蒿素联合疗法治疗疟疾时要谨慎。因此,建议加大给药间隔以避免遗传损伤风险。