Noguchi Chihiro, Matsue Kenta, Nakanishi Yutaka, Asanuma Fumiko, Miyata Hiroto, Sasaki Minoru
1 Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
2 Regulatory Affairs Division, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
Toxicol Pathol. 2019 Jan;47(1):73-81. doi: 10.1177/0192623318811836. Epub 2018 Nov 20.
We evaluated the growth plates (GPs) of rats after a 14-day reduction in food consumption caused by either daily oral dosing with 5-fluorouracil (5-FU: a positive control reducing food consumption and affecting the GPs) or a direct reduction in food consumption to determine whether the observed changes were attributable to a direct effect of drug toxicity. Histomorphometric analyses of the femoral GP were performed for a nontreated (NT) control group, three groups treated with 5-FU (12, 15, and 18 mg/kg/day) and three groups with food intake restricted to levels corresponding to those consumed by the rats in the three 5-FU-treated groups. Compared with the NT group, the GP widths and the number of chondrocytes in the proliferative zone decreased significantly in all the 5-FU-treated groups and the dietary restriction groups. Importantly, no significant differences between the 5-FU-treated groups and the groups with matched dietary restrictions were seen for most parameters. Thus, the 14-day dietary restriction caused significant changes in the proliferative zone of the GP, and similar changes observed in the 5-FU-treated groups were presumed to result from the comparable reduction in food intake rather than being a direct toxic effect of the drug.
我们评估了大鼠的生长板（GP），这些大鼠通过每日口服5-氟尿嘧啶（5-FU：减少食物消耗并影响生长板的阳性对照）或直接减少食物消耗导致食物摄入量减少14天，以确定观察到的变化是否归因于药物毒性的直接作用。对一个未处理（NT）对照组、三个用5-FU治疗的组（12、15和18mg/kg/天）以及三个食物摄入量限制在与三个5-FU治疗组大鼠所消耗水平相当的组进行了股骨生长板的组织形态计量学分析。与NT组相比，所有5-FU治疗组和饮食限制组的生长板宽度和增殖区软骨细胞数量均显著减少。重要的是，在大多数参数上，5-FU治疗组与饮食限制匹配组之间没有显著差异。因此，14天的饮食限制导致生长板增殖区发生显著变化，在5-FU治疗组中观察到的类似变化被认为是由于食物摄入量的相应减少，而不是药物的直接毒性作用。
