Beneficial effects of Pimpinella anisum L. ethanol and aqueous extracts on L-asparaginase-associated hepatotoxicity using specific 99mTc-Phytate biodistribution studies in rats

Introduction: The present study aimed to investigate the protective effects of Pimpinella anisum L. ethanolic and aqueous extracts on L-asparaginase- associated hepatotoxicity in rats using histopathological and specific 99mTc-Phytate biodistribution studies. Materials and Methods: 60 female rats were divided into 9 treatment groups including L-asparaginase group, Aqueous extract (100 and 200 mg/kg), Ethanolic extract (100 and 200 mg/kg), Aqueous extract (100 mg/kg) + L-asparaginase, Aqueous extract (200 mg/kg) + L-asparaginase, Ethanolic extract (100-100 mg/kg) + L-asparaginase, and Ethanolic extract (200 mg/kg) + L-asparaginase and one control group. L-asparaginase was intraperitoneally injected at a dose of 1000 IU/Kg every other day for a week. Aqueous and ethanolic extracts of P. anisum were given by gavage technique for seven consecutive days. 24h after the last day of treatment, 99mTc-phytate was intravenously injected and then, rats were killed with a lethal dose of ketamine/xylazine. Vital organs were removed, weighed, and their activity was counted by a gamma counter. 99mTc-phytate scintigraphy and histopathological assessment were performed for further evaluation. Results: L-asparaginase-induced liver toxicity was significantly reduced with ethanolic extract in L-asparaginase-treated rats (P˂0.05). It is worth mentioning that the aqueous extract of Anise seed led to hepatotoxicity (P˂0.05) which is likely to be mainly due to contamination of the plant with the toxic pyrrolizidine alkaloids. Conclusion: P. anisum ethanolic extract due to the presence of anethole and phenolic compounds can ameliorate L-asparaginase-induced hepatotoxicity in rats.