Abstract：
Intravenous and oral 14 d repeated dose toxicity studies of Trichostatin A (TSA) were carried out in Swiss albino mice using low, intermediate, and high doses. Intravenous doses were 10, 25, and 50 μg/kg b.w while the oral doses were 20, 50, and 100 μg/kg b.w. Respective control groups of mice were administered phosphate buffered saline (vehicle only) for 14 consecutive days. All external morphological, hematological, biochemical, urine, histopathological, food intake in addition to body weight and vital organ weight were recorded. During the study no mortality in any animal was observed in either treatment routes. There were no significant changes in morphology, food intake, hematology, biochemical, urine analysis, organ weight. Animals treated high dose of TSA intravenously (50 μg/kg b.w) and orally (100 μg/kg b.w) had enlarged, congested, and discolored kidneys which were statistically significant. Histopathological studies had shown statistically significant degenerated glomerulus in high dose of intravenous and orally treated animals and degenerated tubule were found in orally treated animals. Genotoxicity was evaluated using micronucleus frequency at 14 and 21 d after treatment and chromosomal aberration at 21 d after treatment. Micronucleaus assay and chromosomal assay however did not show any significant changes at any doses and administration routes. Therefore, this study concludes that dose ∼25 µg/kg and ∼50 µg/kg b.w may be considered as No Observed Adverse Effect Level (NOAEL) for intravenous and oral administration of TSA respectively.
摘要：
在瑞士白化病小鼠中使用低剂量进行了TrichostatinA（TSA）的静脉和口服14d重复剂量毒性研究，中间,和高剂量。静脉内剂量为10、25和50μg/kgb.w,而口服剂量为20、50和100μg/kgb.w.各对照组小鼠连续14天施用磷酸盐缓冲盐水(仅载体)。所有外部形态，血液学,生物化学，尿液,组织病理学,除体重和重要器官重量外，还记录了食物摄入量。在研究期间,在任一治疗途径中均未观察到任何动物的死亡。形态没有明显变化,食物摄入量,血液学,生物化学，尿液分析,器官重量。静脉内（50μg/kgb.w）和口服（100μg/kgb.w）高剂量TSA治疗的动物已经扩大，拥塞,肾脏变色，具有统计学意义。组织病理学研究表明，在高剂量的静脉和口服治疗的动物中，肾小球变性具有统计学意义，在口服治疗的动物中发现了变性的小管。使用治疗后14和21d的微核频率和治疗后21d的染色体畸变评估遗传毒性。然而,微细胞核测定和染色体测定在任何剂量和施用途径下均未显示任何显著变化。因此,这项研究得出的结论是，剂量~25µg/kg和~50µg/kgb.w可以分别被认为是静脉和口服TSA的未观察到的不良反应水平（NOAEL）。
