Zhang Min, Li Xueyan, Zhao Qiping, She Rufeng, Xia Suhan, Zhang Keyu, Zhang Lifang, Wang Xiaoyang, Wang Mi, Liu Yingchun, Wang Chunmei, Zhang Jie, Xue Feiqun, Fei Chenzhong
Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
Zhejiang Hisun Animal Healthcare Products Co. Ltd., Zhejiang 311400, PR China.
Vet Parasitol. 2019 Mar;267:4-8. doi: 10.1016/j.vetpar.2019.01.006. Epub 2019 Jan 29.
The objective of present studies was to evaluate and compare the anticoccidial activity of triazine compounds in broiler chickens infected with E. tenella, E. necatrix, E. acervulina, E. maxima, and two field mixed Eimeria species. The anticoccidial efficacy was evaluated using the anticoccidial index (ACI). The results showed that Aminomizuril (AZL) and Ethanamizuril (EZL) were active metabolites of nitromezuril, which demonstrated excellent effectiveness against E. tenella, E. necatrix, E. acervulina, E. maxima, and the field Eimeria isolates in broiler chickens at a dosage of 10 mg/kg in feed. The anticoccidial activities of AZL and EZL at dose 10 mg/kg were roughly equivalent to the parent nitromezuril at a dosage of 3 mg/kg in feed. The decrease in metabolite anticoccidial activity is probably due to an increasing polarity of compounds in the metabolic processes. The sensitivity of two field Eimeria isolates to triazines EZL, diclazuril and toltrazuril was tested using 4 indices including anticoccidial index (ACI), percent of optimum anticoccidial activity (POAA), reduction of lesion scores (RLS) and relative oocysts production (ROP). Results showed that the sensitivity of EZL treatment against the two field Eimeria isolates were relatively superior to that of diclazuril and toltrazuril treatment. The field Eimeria isolates from Gansu Province was determined to be slightly, moderately and highly resistant to EZL, diclazuril and toltrazuril respectively. The field Eimeria isolates from Zhejiang Province was slightly, highly and slightly resistant to EZL, diclazuril and toltrazuril respectively. The results above indicated that the anticoccidial activity of metabolites was lower than that of the parent nitromezuril and there was partial cross-resistance among triazines EZL, diclazuril and toltrazuril. However the field Eimeria isolates had higher sensitive to EZL than the triazines diclazuril and toltrazuril. It was suggested that the site of C4 substituents of phenol of triazine anticoccidials may have important biological functions and the metabolite EZL would be a potential novel anticoccidial agent worthy of more attention.
本研究的目的是评估和比较三嗪类化合物对感染柔嫩艾美耳球虫、毒害艾美耳球虫、堆型艾美耳球虫、巨型艾美耳球虫以及两种现场混合艾美耳球虫种类的肉鸡的抗球虫活性。使用抗球虫指数（ACI）评估抗球虫效力。结果表明，氨丙嘧吡啶（AZL）和乙胺丙嘧吡啶（EZL）是硝丙嘧吡啶的活性代谢产物，其在饲料中剂量为10 mg/kg时，对肉鸡体内的柔嫩艾美耳球虫、毒害艾美耳球虫、堆型艾美耳球虫、巨型艾美耳球虫以及现场艾美耳球虫分离株显示出优异的效果。AZL和EZL在10 mg/kg剂量时的抗球虫活性大致相当于饲料中3 mg/kg剂量的母体硝丙嘧吡啶。代谢产物抗球虫活性的降低可能是由于化合物在代谢过程中极性增加。使用包括抗球虫指数（ACI）、最佳抗球虫活性百分比（POAA）、病变评分降低（RLS）和相对卵囊产量（ROP）在内的4个指标测试了两种现场艾美耳球虫分离株对三嗪类化合物EZL、地克珠利和妥曲珠利的敏感性。结果表明，EZL处理对两种现场艾美耳球虫分离株的敏感性相对优于地克珠利和妥曲珠利处理。来自甘肃省的现场艾美耳球虫分离株分别被确定为对EZL、地克珠利和妥曲珠利有轻度、中度和高度抗性。来自浙江省的现场艾美耳球虫分离株分别对EZL、地克珠利和妥曲珠利有轻度、高度和轻度抗性。上述结果表明，代谢产物的抗球虫活性低于母体硝丙嘧吡啶，并且三嗪类化合物EZL、地克珠利和妥曲珠利之间存在部分交叉抗性。然而，现场艾美耳球虫分离株对EZL的敏感性高于三嗪类化合物地克珠利和妥曲珠利。提示三嗪类抗球虫药酚类C4取代基位点可能具有重要生物学功能，代谢产物EZL将是一种值得更多关注的潜在新型抗球虫药。
