Gürsoy Muhammed Taha, Çavuşoğlu Kültiğin, Yalçin Emine, Acar Ali
Department of Biology, Institute of Science, Giresun University, Giresun, Turkey.
Department of Biology, Faculty of Art and Science, Giresun University, 28200, Giresun, Turkey.
Sci Rep. 2025 Sep 26;15(1):33015. doi: 10.1038/s41598-025-18500-1.
In this study, the biochemical and cytogenetic toxicity induced by the antibiotic active ingredient ornidazole in the non-target organism Allium cepa L. was investigated. In the toxicity assessment, the level of malondialdehyde (MDA), a biochemical marker of lipid peroxidation; genotoxicity indicators such as micronucleus (MN) frequency and mitotic index (MI); the incidence of chromosomal abnormalities (CAs); activities of antioxidant defense enzymes catalase (CAT) and superoxide dismutase (SOD); and the levels of chlorophyll a and b pigments reflecting photosynthetic capacity were analyzed. Additionally, DNA damage was assessed using the Comet test method, and the interaction of ornidazole with macromolecules-particularly DNA-was examined using the molecular docking approach. Four groups of A. cepa bulbs-one control and three treatments-were created. Three distinct dosages (0.0179, 0.0357 and 0.0714 mg/L) of ornidazole were used to germinate the bulbs in the treatment group, while tap water was used to germinate the bulbs in the control group. Following germination, samples from the roots and leaves were gathered and ready for examination. As a result, there was no cytogenetic damage or biochemical alteration that was statistically significant (p > 0.05) in the control group (Group I). MI value, DNA, and chlorophyll levels significantly (p < 0.05) decreased with ornidazole treatment, while MN frequency, CAs, MDA levels, SOD, and CAT activities significantly (p < 0.05) increased. At the ornidazole dosage of 0.0714 mg/L, these rises and declines were shown to be more noticeable. Ornidazole promoted several CAs in root meristem cells, the most common being the sticky chromosome. DNA damage was highlighted by the comet assay results, which indicated a drop in head DNA and an increase in tail DNA. In the control group, the Tail DNA was 1.00 ± 1.05 (%), whereas in the group treated with 0.0714 mg/L ornidazole, it increased to 72.0 ± 1.63 (5), indicating high DNA fragmentation. Molecular docking results showed ornidazole-DNA, ornidazole-tubulin, ornidazole-topoisomerase, ornidazole-glutamate-1-semialdehyde aminotransferase and ornidazole-protochlorophyllide reductase interaction supporting the biochemical and cytogenetic toxicity results. In conclusion, ornidazole exposure induced significant toxic effects in the non-target organism Allium cepa. The study further validated the efficacy of the Allium test as a reliable bioassay for detecting such toxicity. These findings underscore the urgent need for implementing appropriate environmental management strategies to mitigate pharmaceutical contamination and protect non-target organisms from drug-induced toxicity.
在本研究中，调查了抗生素活性成分奥硝唑对非靶标生物洋葱（Allium cepa L.）诱导的生化和细胞遗传毒性。在毒性评估中，分析了脂质过氧化的生化标志物丙二醛（MDA）水平；遗传毒性指标，如微核（MN）频率和有丝分裂指数（MI）；染色体异常（CA）的发生率；抗氧化防御酶过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的活性；以及反映光合能力的叶绿素a和b色素水平。此外，使用彗星试验方法评估DNA损伤，并使用分子对接方法研究奥硝唑与大分子（特别是DNA）的相互作用。创建了四组洋葱鳞茎——一组对照和三组处理。在处理组中，使用三种不同剂量（0.0179、0.0357和0.0714 mg/L）的奥硝唑使鳞茎发芽，而在对照组中使用自来水使鳞茎发芽。发芽后，采集根和叶的样本并准备进行检查。结果，对照组（第一组）没有出现具有统计学意义（p＞0.05）的细胞遗传损伤或生化改变。随着奥硝唑处理，MI值、DNA和叶绿素水平显著（p＜0.05）下降，而MN频率、CA、MDA水平、SOD和CAT活性显著（p＜0.05）增加。在奥硝唑剂量为0.0714 mg/L时，这些上升和下降更为明显。奥硝唑在根尖分生组织细胞中引发了多种CA，最常见的是粘连染色体。彗星试验结果突出了DNA损伤，表明头部DNA减少，尾部DNA增加。在对照组中，尾部DNA为1.00±1.05（%），而在使用0.0714 mg/L奥硝唑处理的组中，它增加到72.0±1.63（%），表明DNA高度碎片化。分子对接结果显示奥硝唑与DNA、奥硝唑与微管蛋白、奥硝唑与拓扑异构酶、奥硝唑与谷氨酸-1-半醛转氨酶以及奥硝唑与原叶绿素酸还原酶的相互作用，支持了生化和细胞遗传毒性结果。总之，奥硝唑暴露在非靶标生物洋葱中诱导了显著的毒性作用。该研究进一步验证了洋葱试验作为检测此类毒性的可靠生物测定方法的有效性。这些发现强调了迫切需要实施适当的环境管理策略，以减轻药物污染并保护非靶标生物免受药物诱导的毒性。
