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Application of a DSS colitis model in toxicologically assessing norisoboldine.

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
Source :
Toxicology Mechanisms & Methods. Feb2020, Vol. 30 Issue 2, p107-114. 8p. 2 Color Photographs, 4 Graphs.
Publication Year :
2020

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15376516
Volume :
30
Issue :
2
Database :
Academic Search Index
Journal :
Toxicology Mechanisms & Methods
Publication Type :
Academic Journal
Accession number :
141231842
Full Text :
https://doi.org/10.1080/15376516.2019.1669242