Study of Genotoxic Assays and 28-Day Repeated Dose Oral Toxicity in Rats of Antrocin

• Main Authors: Yi-Hui Su, 蘇浥慧
• Other Authors: 廖俊旺
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107NCHU5628002%22.&searchmode=basic

碩士 === 國立中興大學 === 獸醫病理生物學研究所 === 107 === Antrocin, a novel compound of sesquiterpene lactones, was first isolated from Antrodia cinnamomea in 1995. In recent studies, antrocin showed great anti-tumor potency by interfering signaling pathways of cancer cell growth, invasion and migration. Moreover, antrocin can induce tumor cells apoptosis. These findings suggest the therapeutic potential of antrocin. Pure antrocin extract from Antrodia cinnamomea fruiting bodies is very rare. To obtain antrocin for medicinal purposes, the invention of synthesis approaches. However the toxicity of antrocin has not been evaluated. In our study, we aimed to evaluate the genotoxic effects of antrocin by using different studies, including bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test, and in vivo mammalian erythrocyte micronucleus test. Besides, we conducted a 28-day oral toxicity test at 7.5 mg/kg and 37.5 mg/kg of antrocin in Sprague-Dawley(SD) rats. Sorafenib, an anti-tumor drug, was used as positive control for toxicity comparison. During the study period, we recorded clinical signs, mortality and morbidity of rats. Clinical pathology examinations including hematology, serumchemistry and urine analysis were performed after the test period. Histopathology examinations were performed to ensure any possible toxicity of antrocin in rats. In the results of genotoxicity assays, antrocin showed no mutagenic evidence in Salmonella Typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 in bacterial reverse mutation test, with or without S9 mixture. In addition, antrocin, in the dose of 100 μg/mL, did not induce significant chromosome damage in CHO-K1 cells after co-culture for 3 or 19 hours. In in vivo mammalian erythrocyte micronucleus test, ICR mice were treated with 250 mg/kg antrocin by oral gavage. Blood samples were collected 48 and 72 hours later, and the samples were analyzed by flow cytometry. Data showed that antrocin did not increase the percentage of reticulocytes and micronucleus. In oral toxicity test, clinical pathology examinations and histopathology examinations revealed that no treatment related signs of toxicity were found in antrocin-treated groups. In positive control group, rough hair, liver-associated enzymes elevation, and multi-organ toxicity were observed. In conclusion, antrocin has no potential of mutagenicity and genotoxicity. According to the result of 28-day oral toxicity in rats, the no observed adverse effect level (NOAEL) of antrocin is 37.5 mg/kg/day in rats.