Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2005; 11(5): 665-671
Published online Feb 7, 2005. doi: 10.3748/wjg.v11.i5.665
Toxicity of novel anti-hepatitis drug bicyclol: A preclinical study
Geng-Tao Liu, Yan Li, Huai-Ling Wei, Hong Lu, Hui Zhang, Yu-Gui Gao, Ling-Zhi Wang
Geng-Tao Liu, Yan Li, Huai-Ling Wei, Hong Lu, Hui Zhang, Yu-Gui Gao, Ling-Zhi Wang, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Author contributions: All authors contributed equally to the work.
Supported by the Grant From Ministry of Sciences and Technology of China, No.96-901-01-45
Correspondence to: Professor Geng-Tao Liu, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, 1 Xian Nong Tan St, Beijing 100050, China. liugt@imm.ac.cn
Telephone: +86-10-63165178 Fax: +86-10-63017757
Received: July 23, 2004
Revised: July 26, 2004
Accepted: September 4, 2004
Published online: February 7, 2005
Abstract

AIM: To study the toxicity of bicyclol to animals.

METHODS: Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d. Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol [150, 300, 600 mg/kg, 100-400 folds corresponding to the proposed therapeutic dose (1.5 mg/(kg·d)) of bicyclol for patients] once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2% sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6, 50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames’s test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.

RESULTS: The oral LD50 of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.

CONCLUSION: Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

Keywords: Bicyclol; Antiviral agents; Toxicity test