Uji Efek Toksik Senyawa {1,3 Bis (P-Hydroxyphenyl)Urea} terhadap Tikus Putih Betina (Rattus norvegicus L.) dan Efek Teratogenik terhadap Fetus Tikus Putih

Abstract

Non steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs for pregnant women to treat fever, pain and inflammation. Several studies have provided evidence that NSAIDs cross the placenta in humans and reach the fetal circulation and cause side effects such as miscarriage, congenital heart disease, vascular, brain, kidney and lung effects. {1,3 bis (p-Hydroxyphenyl)urea} is a modified p-aminophenol compound which has more potent analgesic and anti-inflammatory activity and has fewer hepatotoxic side effects. This research is a continuation of previous research which aims to prove whether the compound {1,3 bis (p-Hydroxyphenyl)urea} has a toxic effect on white rats and a teratogenic effect on white rat fetuses. Tests for toxic effects and teratogenic effects were carried out by giving the test preparations to pregnant rats which had been divided into 5 groups namely negative control group (CMC-Na 0.5%), positive control (Gabapentin 50 mg/kgBB), compound {1.3 bis (p-Hydroxyphenyl)urea} at doses of 50, 500 and 1000 mg/kgBW during organogenesis. Observation of the toxic effects of pregnant rats included body weight, clinical toxic symptoms, feed consumption, T3 hormone levels and death. Observations for teratogenic effects include resorption, hemorrhage and death of the fetus, body weight, body length, number of fetuses, observations of external malformations and skeletal malformations. Based on the results of the study, the toxic effect on pregnant rats showed that the body weight of the compound group {1,3 bis (p-Hydroxyphenyl)urea} doses of 50, 500 and 1000 mg/kg BW did not show a significant difference when compared to the negative control group (p>0.05 ). On observation of clinical toxic symptoms and death, all control groups and the test group did not show clinical toxic symptoms and death. In observing the feed consumption of pregnant rats, there was no significant difference in each group (p>0.05). Observation of T3 hormone levels showed that all groups of compounds {1,3 bis (p-Hydroxyphenyl)urea} did not have a significant difference when compared to the negative control group (p>0.05). Based on the results of research on teratogenic effects, it was found that the group of compounds {1,3 bis (p-Hydroxyphenyl)urea} at a dose of 1000 mg/kgBB had external malformations characterized by hemorrhage on the back, legs, arms and head of the fetus. On skeletal observation, there were malformations of the trunk, forelegs and hind paws in the compound group {1,3 bis (p-Hydroxyphenyl)urea} at a dose of 1000 mg/kgBW. The compound {1,3 bis (p-Hydroxyphenyl)urea} has a teratogenic effect at a dose of 1000 mg/kg and therefore must be used with caution in pregnancy.