Anti-inflammatory activity and toxicity evaluation of 1,3-bis(p-hydroxyphenyl)urea

Background: Inflammation is a normal protective response caused by tissue damage through physical trauma, chemical damage, or invasion of pathogenic microorganisms. 1,3-bis(p-hydroxyphenyl)urea is a modified p-aminophenol compound, which is considered to have strong analgesic activity based on cyclooxygenase-2 inhibition and has fewer hepatotoxic side effects. In-silico test showed 1,3-bis(p-hydroxyphenyl)urea has COX-1 and TNF- binding activity, so it has the potential to be developed as an anti-inflammatory agent. Anti-inflammatory activity was tested using mice. Toxicity test was conducted to test the safety of 1,3-bis(p-hydroxyphenyl)urea. Methods: Anti-inflammatory test was carried out by measuring the percentage of inflammation in rat paws using a plethysmometer after administration of 1,3-bis(p-hydroxyphenyl)urea induced by carrageenan 1%, and then histology was performed to observe the number of neutrophils. A toxicity test using OECD guidelines carried out acute toxicity for 24 hours and was observed for 14 days. The subchronic toxicity test was carried out for 28 days, followed by 42 days in the satellite group. Results: Analysis of rat paw inflammation volume showed 1,3-bis(p-hydroxyphenyl)urea could suppress inflammation after carrageenan-1% induction. The group given {1.3 bis (p-Hydroxyphenyl)urea} and sodium diclofenac 2.25 mg/kg BW had a significant difference in results (p<0.05) with 0.5% Na CMC group. Doses of 50, 100, and 200 mg/kg BW showed no significant difference (p>0.05) with diclofenac sodium. The number of neutrophils also decreased compared to the 0.5% Na CMC group. The acute toxicity test of 1,3-bis(p-hydroxyphenyl)urea did not cause toxic symptoms and death up to a dose of 5000 mg/kg BW. The microscopic results of subchronic toxicity of liver tissue experienced hydropic degeneration at a dose of 1000 mg/kg BW; in the lungs causes congestion, and microscopic renal tissue undergoes Bowman space dilatation and tubular lumen dilatation, but this condition is reversible. Conclusion: This 1,3-bis(p-hydroxyphenyl)urea compound had an anti-inflammatory activity and relatively low toxicity.