Federal Rural University of Amazônia - UFRA, Belém, Pará.
Federal University of Pará - UFPA, Belém, Pará.
Drug Chem Toxicol. 2024 Sep;47(5):527-533. doi: 10.1080/01480545.2023.2217478. Epub 2023 Jun 8.
Despite the cytotoxicity and embryotoxicity previously reported artesunate is a recommended drug to treat malaria for adults, children, and women in the first trimester of pregnancy. To address the putative effects of artesunate on female fertility and preimplantation embryo development, when the pregnancy is not detectable yet, artesunate was added to the oocyte maturation and embryo development of bovine. Briefly, in experiment 1 the cumulus-oocyte complexes (COCs) were matured for 18 h with 0.5, 1, or 2 µg/mL of artesunate or not (negative control) and then checked for nuclear maturation and subsequent embryo development. In experiment 2, the COCs were matured and fertilized without artesunate, which was added (0.5, 1, or 2 µg/mL) from the 1st to the 7th day of embryo culture along with a negative and a positive control group with doxorubicin. As a result, the use of artesunate on oocyte maturation did not differ from the negative control ( > 0.05) regarding nuclear maturation, cleavage, and blastocyst formation. Also, artesunate on embryo culture did not differ from negative control ( > 0.05) regarding cleavage and blastocyst formation, except for positive control, with doxorubicin ( < 0.05). In conclusion, under the conditions investigated, there was no evidence of artesunate toxicity on oocyte competence and the preimplantation period of embryo development in the bovine model, however, artesunate use still should be taken carefully as the outcome of implantation after oocytes and blastocysts exposure to artesunate remains unknown.
尽管青蒿琥酯先前被报道具有细胞毒性和胚胎毒性，但它仍是治疗成人、儿童和妊娠首三月妇女疟疾的推荐药物。为了研究青蒿琥酯对女性生育力和着床前胚胎发育的潜在影响，在妊娠尚不可检测时，将青蒿琥酯添加到牛卵母细胞成熟和胚胎发育中。简要地，在实验 1 中，卵丘-卵母细胞复合物（COCs）用 0.5、1 或 2μg/ml 的青蒿琥酯或无药物（阴性对照）成熟 18 小时，然后检查核成熟和随后的胚胎发育。在实验 2 中，COCs 未用青蒿琥酯成熟和受精，从胚胎培养的第 1 天到第 7 天添加（0.5、1 或 2μg/ml）青蒿琥酯，同时设阴性和阳性对照组，用阿霉素处理。结果，青蒿琥酯对卵母细胞成熟的作用与阴性对照组（>0.05）无差异，核成熟、卵裂和囊胚形成均无差异。此外，青蒿琥酯对胚胎培养的作用与阴性对照组（>0.05）无差异，除了阳性对照组，用阿霉素处理（<0.05）。总之，在所研究的条件下，没有证据表明青蒿琥酯对牛模型的卵母细胞功能和胚胎着床前发育有毒性，但仍应谨慎使用青蒿琥酯，因为卵母细胞和囊胚暴露于青蒿琥酯后的植入结果尚不清楚。
