Anti-inflammatory activity and toxicity evaluation of 1,3-bis(p-hydroxyphenyl)urea [version 2; peer review: 1 approved with reservations, 1 not approved]

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. Antiinflammatory 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 compound had an anti-inflammatory activity and relatively low toxicity. between 1-5 h. This indicated that the test group had anti-inflammatory activity at 1-5 h. The results also showed a marked accumulation of neutrophils in the legs, with the least occurrence observed in the diclofenac sodium and 1,3 bis ( p -hydroxyphenyl) urea groups, at 200, 100, and 50 mg/kg BW. Neutrophils are cells carrying out the phagocytosis of foreign bodies when they rapidly increase. This indicates that inflammation occurs and lasts longer when there is no infection. During an injury, these cells are always the first to occur at the damaged tissues at approximately 24-48 h. After the third day of infection, neutrophils rapidly increase within the injury and are more activated by macrophage cells. 15,16 Based on an acute response, these cells caused degranulation and lysis through a fatal enzyme. This was because neutrophil lysosomal granules contained hydrolytic and proteolytic enzymes, in addition to ROS source catalysts (mainly NADPH and myeloperoxidase). Therefore, damages to various biological molecules were observed when lysis and enzymes were spilled intothe tissue. In addition, live neutrophils are an essential factor in the inflammatory response. 17,18 Although 1,3-bis( p -hydroxyphenyl) urea increased body weight when compared to the control group, it was still not significant. This was because clinical signs and symptoms were sensitive indications of poisoning. In this study, the animals were regularly monitored and assessed based on clinical signs and body weight. In addition, rapid and severe weight losses were often signs of a health problem, due to lack of food and drink consumption, certain disorders, or toxic symptoms. 34 According to this study, the effects of 1,3-bis( p -hydroxyphenyl) urea on the liver, lungs, kidneys, and liver were indicated by hematological and biochemical markers. In the acute and subchronic toxicity tests, there was no mortality after the administration of the extract at 5000 and 1000 mg/kg BW, respectively. On high-dose treatment, histopathological studies indicated damages to the liver and lungs. The satellite group also showed that all toxic symptoms,as well as biochemical andpathological This article showed that 1,3-bis(p-hydroxyphenyl)urea had anti-inflammatory activity and safe to be used. However the results section in the abstract did not clearly show the efficacy and safety of the compound. Please provide the efficacy with number, percentage or else.