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

<strong>Background: </strong>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 an- ti-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. <strong>Methods: </strong>An anti-inflammatory test was carried out by measuring the per-centage of inflammation in rats, after the administration of 1,3 bis (p-Hydroxyphenyl) urea was previously induced by the carrageenan solution intraplantar and the analy- sis of neutrophil values through a plethysmometer and Hematoxylin-Eosin method. Also, an acute toxicity test was performed by administering this p-aminophenol com- pound 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. <strong>Results:</strong>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 symp-toms were observed in the acute and subchronic tests. <strong>Conlclusion:</strong>This p-aminophenol 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、有害化学物质刺激或病原微生物侵袭诱发。在修饰型对氨基酚（p-aminophenol）类化合物中，1,3-双(对羟基苯基)脲的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（lipophilicity）处于1.8~4.4区间时，可作为抗炎剂发挥效用。因此，在评估1,3-双(对羟基苯基)脲的毒性效应时，明确其安全使用规范十分必要，这与理想药物的有效性与安全性要求高度契合。 方法：本研究先通过角叉菜胶溶液足底注射诱导大鼠炎症模型，给予1,3-双(对羟基苯基)脲后，采用体积描记仪（plethysmometer）与苏木精-伊红（Hematoxylin-Eosin）染色法分别检测大鼠炎症发生率及中性粒细胞计数，以开展抗炎实验。此外，本研究还开展了急性毒性实验：对雌性大鼠给予该对氨基酚类化合物，给药后连续观察24小时并持续监测14天；同时开展亚慢性毒性实验：对雌雄大鼠连续给药28天，停药后继续观察42天。 结果：以50、100及200 mg/kg体重的剂量给予1,3-双(对羟基苯基)脲时，其抗炎活性可与2.25 mg/kg体重剂量的双氯芬酸钠（diclofenac sodium）相媲美。急性与亚慢性毒性实验中均未观察到毒性反应及动物死亡情况。 结论：该对氨基酚类化合物具备明确的抗炎活性，且毒性相对较低。