Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.
Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou, China.
BMC Pharmacol Toxicol. 2023 Oct 13;24(1):54. doi: 10.1186/s40360-023-00696-5.
AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted.
Herein, we performed acute toxicological studies of AT-533 and AT-533 gel in Sprague-Dawley rats. Fifteen-day acute toxicity study of AT-533 was conducted in both male and female Sprague-Dawley rats at doses of 5, 50, 250 and 500 mg/kg and AT-533 gel at 5 g/kg in the study. During experiment, food consumption and mortality were observed and body weight, hematology, serum biochemistry and histopathological assessment of rats were carried out. No abnormal changes were observed in rats percutaneously treated with AT-533 at 5 mg/kg and 50 mg/kg and AT-533 gel. However, loss of appetite and body weight, adverse reactions, toxicologically relevant alterations in hematology and biochemistry were found in rats percutaneously treated with AT-533 at 250 mg/kg and 500 mg/kg during 15-day acute dermic toxicity study.
The aforementioned results suggested that the LD of AT-533 is 228.382 mg/kg and the LD of AT-533 gel is greater than 5 g/kg. These findings indicated that AT-533 is non-toxic in rats when the dose less than 50 mg/kg and AT-533 gel can be considered a gel with no toxicity at doses less than 5 g/kg.
AT-533 是一种新型热休克蛋白 90 抑制剂，具有抗炎、抗病毒和抗肿瘤作用。此外，由 AT-533 作为原料制成的凝胶命名为 AT-533 凝胶，具有修复疱疹病毒感染引起的角膜炎和皮炎的功能。然而，AT-533 和 AT-533 凝胶的急性安全性评价尚未进行。
在此，我们在 Sprague-Dawley 大鼠中进行了 AT-533 和 AT-533 凝胶的急性毒理学研究。在雄性和雌性 Sprague-Dawley 大鼠中进行了为期 15 天的 AT-533 急性毒性研究，剂量分别为 5、50、250 和 500mg/kg，以及 AT-533 凝胶 5g/kg。在实验过程中，观察了大鼠的摄食量和死亡率，并对大鼠的体重、血液学、血清生化和组织病理学进行了评估。经皮给予 5mg/kg 和 50mg/kg 的 AT-533 以及 AT-533 凝胶时，大鼠未见异常变化。然而，在 15 天的急性皮肤毒性研究中，经皮给予 250mg/kg 和 500mg/kg 的 AT-533 时，大鼠出现食欲不振、体重减轻、不良反应以及血液学和生化学毒性相关改变。
上述结果表明，AT-533 的 LD 为 228.382mg/kg，AT-533 凝胶的 LD 大于 5g/kg。这些发现表明，当剂量小于 50mg/kg 时，AT-533 在大鼠中无毒性，当剂量小于 5g/kg 时，AT-533 凝胶可被认为是一种无毒凝胶。
