Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg·BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.

目前，尚未对哺乳动物进行多种兽用抗菌剂的毒理学评估。在这项研究中，我们评估了恩诺沙星 (E) 与粘菌素 (C) 和喹诺酮 (Q) 联合使用的短期毒性。雄性幼鼠连续14天口服混合药物和单一药物，剂量分别为20、80和400 mg/(kg·BW)进行环境毒理学研究。结果表明，在高剂量治疗下，E+C+Q的组合显着降低了大鼠的机体摄入量、淋巴细胞计数；显着增加丙氨酸转氨酶 (ALT)、谷氨酸草酰乙酸转氨酶 (AST) 和胆碱酯酶 (CHE) 的值；它还得到了最严重的组织病理学变化，其中观察到正弦充血和大量黑色颗粒。这意味着高剂量组中的 E + C+Q 能够对肝脏造成显着损害。其他组合或剂量不会引起显着的肝损伤。然后对高剂量组的大鼠进行转录组分析以进行进一步研究。对于 E + C 和 E + Q，过滤掉了 375 和 480 个不同表达的基因，揭示了它们对基因组可能的潜在影响。对于 E+C+Q，进行了加权基因共表达网络分析，并确定了 96 个中枢基因，以揭示这种组合诱导的特定效应。该研究表明，在涉及这些抗菌药物的风险评估时，应考虑关节毒性。然后对高剂量组的大鼠进行转录组分析以进行进一步研究。对于 E + C 和 E + Q，过滤掉了 375 和 480 个不同表达的基因，揭示了它们对基因组可能的潜在影响。对于 E+C+Q，进行了加权基因共表达网络分析，并确定了 96 个中枢基因，以揭示这种组合诱导的特定效应。该研究表明，在涉及这些抗菌药物的风险评估时，应考虑关节毒性。然后对高剂量组的大鼠进行转录组分析以进行进一步研究。对于 E + C 和 E + Q，过滤掉了 375 和 480 个不同表达的基因，揭示了它们对基因组可能的潜在影响。对于 E+C+Q，进行了加权基因共表达网络分析，并确定了 96 个中枢基因，以揭示这种组合诱导的特定效应。该研究表明，在涉及这些抗菌药物的风险评估时，应考虑关节毒性。进行了加权基因共表达网络分析，并确定了 96 个中枢基因，以揭示这种组合诱导的特定效应。该研究表明，在涉及这些抗菌药物的风险评估时，应考虑关节毒性。进行了加权基因共表达网络分析，并确定了 96 个中枢基因，以揭示这种组合诱导的特定效应。该研究表明，在涉及这些抗菌药物的风险评估时，应考虑关节毒性。