Author list of Anti-Inflammatory Activity and Toxicity Evaluation of 1,3-bis(p-Hydroxyphenyl)urea

Background: Inflammation is a normal protective response caused by an injury or tissue damage, through physical trauma, damaging chemicals, or invasion of pathogenic microorganisms. One of the modified p-aminophenol compounds is 1,3-bis(p-hydroxyphenyl)urea, which was estimated to have more potent analgesic activity and fewer hepatotoxic side effects than paracetamol. When the lipophilicity of this compound increases between 1.8 to 4.4, it is observed to serve as an anti-inflammatory agent. Therefore, the determination of safety precaution is very necessary while testing for the toxicity effect of 1,3-bis(p-hydroxyphenyl)urea. This is due to the effectiveness and safety of suitable drugs.

Methods: An anti-inflammatory test was carried out by measuring the percentage of inflammation in rats, after the administration of 1,3-bis(p-hydroxyphenyl)urea was previously induced by the carrageenan solution intraplantar and the analysis of neutrophil values through a plethysmometer and Hematoxylin-Eosin method. Also, an acute toxicity test was performed by administering this p-aminophenol compound to female rats for 24 h and observed for 14 days. In addition, a subchronic toxicity test was conducted on male and female rats for 28 days, with continuous observations carried out for 42 days.

Results: The doses of 1,3-bis(p-hydroxyphenyl)urea at 50, 100, and 200 mg/Kg BW, had anti-inflammatory activity compared to diclofenac sodium at 2.25 mg/Kg BW. Also, there is no toxicity and animal death symptoms were observed in the acute and subchronic tests.

Conlclusion: This 1,3-bis(p-hydroxyphenyl)urea compound had an anti-inflammatory activity and relatively low toxicity.

背景：炎症是由损伤或组织损伤引发的正常保护性应答，可由物理创伤、有害化学物质或致病微生物入侵所诱发。对氨基酚类修饰衍生物之一为1,3-双(对羟基苯基)脲，据测算其镇痛活性较对乙酰氨基酚（paracetamol）更强，且肝毒性副作用更少。当该化合物的脂溶性处于1.8至4.4区间时，可作为抗炎剂发挥作用。因此，在开展1,3-双(对羟基苯基)脲的毒性效应测试时，制定安全预防措施十分必要，这一考量基于合格药物的有效性与安全性要求。
方法：本研究通过角叉菜胶（carrageenan）溶液足跖注射诱导大鼠炎症模型，给予1,3-双(对羟基苯基)脲后，采用体积描记法（plethysmometer）及苏木精-伊红（Hematoxylin-Eosin）染色分析法检测中性粒细胞数值，以此评估大鼠的炎症程度，完成抗炎活性测试。此外，本研究开展了急性毒性试验：给雌性大鼠给药该对氨基酚类化合物，给药后观察24小时并持续监测14天。同时，针对雌雄大鼠开展亚慢性毒性试验，给药时长为28天，并持续观察42天。
结果：与剂量为2.25 mg/kg体重的双氯芬酸钠（diclofenac sodium）相比，剂量分别为50、100及200 mg/kg体重的1,3-双(对羟基苯基)脲均表现出抗炎活性。此外，急性与亚慢性毒性试验中均未观察到毒性反应及动物死亡现象。
结论：该1,3-双(对羟基苯基)脲化合物具有抗炎活性，且毒性相对较低。