Annakkaya Numan, Çavuşoğlu Kültiğin, Yalçin Emine, Özkan Burak
Department of Biology, Institute of Science, Giresun University, Giresun, Turkey.
Department of Biology, Faculty of Science and Art, Giresun University, 28200, Giresun, Turkey.
Sci Rep. 2025 Jul 1;15(1):21082. doi: 10.1038/s41598-025-07417-4.
In this study, the toxicity induced by metronidazole, one of the most preferred pharmaceutical active ingredients worldwide, in Allium cepa L, a non-target organism, was investigated. Many genetic (mitotic index = MI, micronucleus = MN and chromosomal abnormalities = CAs) and biochemical (malondialdehyde = MDA, proline, superoxide dismutase = SOD, catalase = CAT, chlorophyll a and b) parameters have been used as indicators of toxicity. Furthermore, the degree of DNA damage caused by metronidazole was investigated by the Comet assay method. On the other hand, metronidazole toxicity was also supported using the in silico method in a computer environment. Four groups of A. cepa bulbs were created, including three treatments and a control. Metronidazole doses of 125, 250, and 500 mg/L were used to germinate the onions in the treatment groups, while tap water was used to germinate the onions in the control group. Samples taken from roots and leaves were used in measurements and physiological examinations. Consequently, the maximum MI value and chlorophyll amounts were measured in the control group. In addition, the lowest MN and CAs numbers, MDA and proline levels, and SOD and CAT activities were also measured in this group. Metronidazole exposure caused notable (p < 0.05) declines in MI value and chlorophyll amounts, and notable increases (p < 0.05) in MN and CAs numbers, MDA and proline levels, and SOD and CAT activities, depending on the dose. Metronidazole exposure promoted CAs such as sticky chromosome, bridge, vagrant chromosome, nuclear bud, and binuclear cell in root meristem cells. Comet assay findings revealed significant decreases (p < 0.05) in the percentage of head DNA and significant increases (p < 0.05) in the percentage of tail DNA depending on the metronidazole dose, and this indicated DNA damage. The in silico study's findings supported the genetic and biochemical toxicity results by showing the direct interaction of metronidazole with DNA, tubulin proteins, topoisomerase enzymes and enzymes responsible for chlorophyll synthesis. Consequently, it has been demonstrated that metronidazole may cause multifaceted toxicity in non-target organisms if it goes beyond its medical use and spreads into the environment. In addition, once more, it has been established that A. cepa is a trustworthy indicator organism for figuring out this toxicity.
在本研究中,对全球最常用的药物活性成分之一甲硝唑在非靶标生物洋葱(Allium cepa L.)中诱导的毒性进行了研究。许多遗传参数(有丝分裂指数=MI、微核=MN和染色体异常=CAs)和生化参数(丙二醛=MDA、脯氨酸、超氧化物歧化酶=SOD、过氧化氢酶=CAT、叶绿素a和b)已被用作毒性指标。此外,采用彗星试验法研究了甲硝唑引起的DNA损伤程度。另一方面,还在计算机环境中使用计算机模拟方法来辅助研究甲硝唑的毒性。创建了四组洋葱鳞茎,包括三个处理组和一个对照组。处理组使用125、250和500mg/L的甲硝唑剂量来使洋葱发芽,而对照组使用自来水使洋葱发芽。从根和叶中采集的样本用于测量和生理检查。结果,对照组中测得的MI值和叶绿素含量最高。此外,该组中MN和CAs的数量、MDA和脯氨酸水平以及SOD和CAT活性也最低。根据剂量不同,甲硝唑暴露导致MI值和叶绿素含量显著下降(p<0.05),MN和CAs数量、MDA和脯氨酸水平以及SOD和CAT活性显著增加(p<0.05)。甲硝唑暴露促使根分生组织细胞中出现如粘连染色体、桥、游离染色体、核芽和双核细胞等染色体异常。彗星试验结果显示,根据甲硝唑剂量不同,头部DNA百分比显著下降(p<0.05),尾部DNA百分比显著增加(p<0.05),这表明存在DNA损伤。计算机模拟研究结果通过显示甲硝唑与DNA、微管蛋白、拓扑异构酶以及负责叶绿素合成的酶之间的直接相互作用,支持了遗传和生化毒性结果。因此,已证明甲硝唑如果超出其医疗用途并扩散到环境中,可能会对非靶标生物造成多方面的毒性。此外,再次证实洋葱是确定这种毒性的可靠指示生物。