Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil.
Department of Teaching, Natural Resources, Design and Infrastructure, Federal Institute of Education, Science and Technology of Pará, Belém, Pará, Brazil.
Drug Chem Toxicol. 2019 Nov;42(6):608-614. doi: 10.1080/01480545.2018.1455207. Epub 2018 Apr 22.
Artemisinin is a substance extracted from the Chinese plant . widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50 µg/mL) and artemether (7.46; 14.92 and 29.84 µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase ( < 0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase ( < 0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.
青蒿素是一种从中国植物中提取的物质，广泛用于天然药物治疗各种疾病。青蒿素是从青蒿素合成的一种物质，这两种药物通常用于治疗疟疾。尽管被认为是有效的抗疟药物，但人们对这些药物的遗传毒性、细胞毒性和致突变性知之甚少。因此，在本研究中，我们使用彗星试验、微核试验和吖啶橙/溴化乙锭染色检测细胞坏死和凋亡的细胞毒性试验，评估了青蒿素（12.5、25 和 50μg/ml）和青蒿琥酯（7.46；14.92 和 29.84μg/ml）在培养的人淋巴细胞中的遗传毒性、致突变性和细胞毒性作用。我们的结果显示，用彗星试验和微核试验测量的 DNA 损伤率以及两种药物处理后的微核频率均显著增加（<0.05）。还观察到只有青蒿素在处理后 48 小时诱导坏死的淋巴细胞数量显著增加（<0.05）。结果表明，这两种药物在培养的人淋巴细胞中诱导致突变、遗传毒性和细胞毒性作用。我们的数据表明，在使用这些药物时需要谨慎，因为遗传毒性/致突变性可能会增加致癌的风险。
