Zhang Suhui, Cheng Xiaoqin, Wang Yu, Fan Junpei, Li Rui, Zhou Su, Liu Shihong, Shi Jingmin, Sun Jie, Hu Yue, Xu Chaojin, Wu Chunhua, Chang Xiuli, Tang Liming, Zhou Zhijun
School of Public Health, Fudan University, Shanghai 200032, China.
Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
Int J Environ Res Public Health. 2015 May 6;12(5):4942-66. doi: 10.3390/ijerph120504942.
The ninety day toxicity and toxicokinetics of fluorochloridone (FLC) were accessed in Wistar rats. Animals were gavaged with FLC at doses of 31.25 mg/kg, 125 mg/kg and 500 mg/kg for ninety days, followed by thirty days for recovery. On the 1st, 60th, 75th and 90th days of the dosing phase, plasma of ten animals of all groups treated with FLC was collected for toxicokinetic analysis of FLC by an UPLC-MS/MS method. Numerous changes in body weight, hematology, serum chemistry, and organ weight ratios were observed by the 45th and 90th dosing day. Most changes in groups treated with FLC were absent on the last recovery day. Testis and epididymis lesions were consistently seen in histopathological observations on the 45th, 90th dosing day and the last recovery day. Repeated administration of FLC increased the level of testosterone in serum in male rats on the 90th dosing day. FLC plasma concentrations could be detected in all animal drug-treated groups during the dosing phase, and a dose proportional relationship was seen between FLC dose and AUC or Cmax. This study will support future studies on the mechanism of FLC-induced toxicity.
在Wistar大鼠中研究了氟咯草酮（FLC）的90天毒性和毒代动力学。动物以31.25 mg/kg、125 mg/kg和500 mg/kg的剂量灌胃给予FLC，持续90天，随后恢复30天。在给药阶段的第1天、第60天、第75天和第90天，收集所有接受FLC治疗组的10只动物的血浆，采用超高效液相色谱-串联质谱法（UPLC-MS/MS）对FLC进行毒代动力学分析。在给药第45天和第90天时，观察到体重、血液学、血清化学和器官重量比出现了许多变化。在最后恢复日，FLC治疗组的大多数变化消失。在给药第45天、第90天和最后恢复日的组织病理学观察中，持续观察到睾丸和附睾病变。重复给予FLC可使雄性大鼠在给药第90天时血清睾酮水平升高。在给药阶段，所有动物药物治疗组均可检测到FLC血浆浓度，并且FLC剂量与AUC或Cmax之间存在剂量比例关系。本研究将为未来关于FLC诱导毒性机制的研究提供支持。
