TERATOGENICITY STUDY OF OLEANOLIC ACID (PENTACYCLIC TRITERPENOID) EXTRACTED FROM ROOT OF LANTANA CAMARA IN WISTAR RATS

Objectives: The aim of the present study was to observe any teratological effects in the fetus parameters anogenital distance (AGD), crown to rump length (CRL), body weight, visceral as well as skeletal structure and dams fertility parameters due to repeated dose administration of oleanolic acid extracted from root of Lantana camara atthe different dose level of 250, 500 and 1000 mg/kg body weight in pregnant dams from implantation day to day before parturition. Furthermore, the aim of this study was to determine the no-observed-adverse-effect level (NOAEL)/lowest-observed-adverse-effect level (LOAEL). Methods: Oleanolic acid was extracted from the roots of L. Camara by the extraction and isolation process. Three treatment groups at the dose level of 250, 500 and 1000 mg prepared in 0.1% between 80 and 0.5% CMC in milli Q water. Doses were administered once daily to pregnant rats from gestation day 5 to GD 19, and on GD 20, rats were terminally sacrificed. Biochemistry, hematology, body weight, feed intake, dam, and fetus parameters were observed. Results: No test item-related significant changes observed in the evaluation of body weight, food, necropsy findings, organ weight, hematology, and biochemistry dam and fetus parameters (AGD, body weight, CRL, visceral and skeletal examination) at the maximum dose level of 1000 mg/kg bwt. Conclusion: There were significant differences observed in the biochemical parameters, such as albumin, alkaline phosphatase, total bilirubin, total cholesterol, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, total protein, and hematology parameters such as hemoglobin, hematocrit, and mean corpuscular volume. These changes are not uniform, dose-dependent, minimal in magnitude, and not correlated with the histopathological findings of the respective organs. On theobservation of results of clinical signs, clinical pathology, histopathological findings, dams and fetus parameters, it may be concluded that NOAEL/LOAEL of test item oleanolic acid extracted from L. camara roots at the highest dose level of 1000 mg/kg body weight when administered orally once daily from gestation day 5 to gestation day 19.