Application of a DSS colitis model in toxicologically assessing norisoboldine. (12th February 2020)

• Record Type: Journal Article
• Authors: Huang, Mincong; Su, Jie; Lou, Zhaohuan; Xie, Feng; Pan, Wei; Yang, Zhengbiao; Gu, Liqiang; Xie, Fang; Xu, Zhiwei; Zhang, Lili; Liu, Fang; Lai, Huimin; Zhang, Lijiang; Lin, Nengming
• Is Part Of: Toxicology mechanisms and methods. Volume 30:Number 2(2020)
• Page Start: 107
• Page End: 114
• Publication Date: 2020-02-12
• Subjects: DSS colitis mouse model -- safety evaluation -- norisoboldine -- programed cell death; Analytical toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology -- Methodology -- Periodicals; 615.907
• DOI: 10.1080/15376516.2019.1669242
• Languages: English
• ISSNs: 1537-6516

Abstract

Abstract: In standard nonclinical drug safety evaluation studies, limitations exist in predicting the clinical risk of a drug based only on data from healthy animals. To obtain more comprehensive toxicological information on norisoboldine (NOR), we conducted an exploratory study using C57BL/6 mice in addition to healthy mice as models of dextran sodium sulfate (DSS) colitis to evaluate the safety of NOR. The healthy mice and DSS colitis mice were exposed to 30 or 90 mg NOR/kg body weight or water for 15 days. Compared with the model control group, 90 mg/kg of NOR aggravated the symptoms and colonic lesions of the DSS colitis mice and even caused death in two animals. No significant adverse effects were observed in the healthy mice. These different toxic reactions to NOR in the healthy and DSS colitis mice indicate that NOR toxicity varies by status among animals and suggests that the DSS colitis mouse model may be more susceptible, accurate and comprehensive in evaluating the safety of NOR. In conclusion, 90 mg/kg of NOR may be safe for healthy mice but not for DSS colitis mice. The DSS colitis mouse model, with many features similar to those of human colitis patients, may be a novel choice to counteract the deficiencies of using healthy mice to evaluate the safety of anti-inflammatory bowel disease (IBD) drugs, and further research is required.