Adil Muhammad, Iqbal Waheed, Adnan Fazal, Wazir Shabnam, Khan Imran, Khayam M Umar, Kamal Mohammad Amjad, Ahmad Shafiq, Ahmed Jawad, Khan Ishaq N
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan.
Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar 25100, Pakistan.
Curr Drug Metab. 2018;19(11):902-909. doi: 10.2174/1389200219666180329124130.
Metronidazole (MTZ) is a synthetic derivative of nitroimidazole that has been widely used for the treatment of several bacterial and parasitic infections including trichomoniasis, amoebiasis, giardiasis, liver abscess, gingivitis, syphilis and phagedena. Scientists have evaluated its carcinogenicity in preclinical in vitro and in vivo studies.
Google scholar and Pubmed search engines were used to construct historic timeline after discovery of MTZ with a journey of ~3 decades of research. Similar search was conducted for its in vivo carcinogenic activities, further extended to elaborate its role in carcinogenicity in humans.
In addition to preclinical in vitro validation of DNA damage, MTZ has been reported to induce cancer in a variety of animal models including lung cancer, malignant lymphomas, breast cancer, hepatocellular carcinoma, pituitary tumors, testicular neoplasms and uterine cancer. Several retrospective cohort studies have reported MTZ as a potential risk factor for lung cancer (n = 771), cervical cancer (n = 2500), breast cancer (n = 2), cholangiocarcinoma (n = 1), and neuroblastoma (n = 28). So far, all the reported data have confirmed MTZ carcinogenicity in animals; however it is still controversial in humans. Based on previous observations, the oxidative metabolites from MTZ are shown to have more carcinogenic effects than the parent drug itself.
Due to potent carcinogenic behaviour, use of MTZ for animals' treatment and its uses in animal food products is prohibited in USA and European countries; however its clinical use in human population is still increasing. Therefore, regular research studies are required to explicate its mechanism/s involved in carcinogenesis.
甲硝唑（MTZ）是一种硝基咪唑的合成衍生物，已被广泛用于治疗多种细菌和寄生虫感染，包括滴虫病、阿米巴病、贾第虫病、肝脓肿、牙龈炎、梅毒和蚀疮。科学家们已在临床前的体外和体内研究中评估了其致癌性。
利用谷歌学术和PubMed搜索引擎构建了MTZ发现后的历史时间表，涵盖了约30年的研究历程。对其体内致癌活性进行了类似的搜索，并进一步扩展以阐述其在人类致癌性中的作用。
除了临床前体外DNA损伤验证外，据报道MTZ在多种动物模型中可诱发癌症，包括肺癌、恶性淋巴瘤、乳腺癌、肝细胞癌、垂体肿瘤、睾丸肿瘤和子宫癌。几项回顾性队列研究报告称MTZ是肺癌（n = 771）、宫颈癌（n = 2500）、乳腺癌（n = 2）、胆管癌（n = 1）和神经母细胞瘤（n = 28）的潜在危险因素。到目前为止，所有报告的数据都证实了MTZ在动物中的致癌性；然而，在人类中仍存在争议。根据以往的观察，MTZ的氧化代谢产物显示出比母体药物本身更强的致癌作用。
由于其强大的致癌行为，美国和欧洲国家禁止将MTZ用于动物治疗及其在动物食品中的使用；然而，其在人类中的临床应用仍在增加。因此，需要定期进行研究以阐明其致癌机制。
