UNIT 21.10 Evaluation of Gastric Ulcerogenic and Healing Impairment Effects of Bisphosphonates: Adverse Gastric Reactions of Bisphosphonate
Published Online: 1 AUG 2012
Copyright © 2012 by John Wiley & Sons, Inc.
Lab Protocol Title
Current Protocols in Toxicology
How to Cite
Takeuchi, K. and Amagase, K. 2012. Evaluation of Gastric Ulcerogenic and Healing Impairment Effects of Bisphosphonates: Adverse Gastric Reactions of Bisphosphonate. Current Protocols in Toxicology. 53:21.10:21.10.1–21.10.29.
- Published Online: 1 AUG 2012
Bisphosphonates (BPPs) were developed as antiresorptive drugs capable of treating diseases related to bone remodeling; however, they have untoward effects including ulceration in the upper gastrointestinal tract and worsen the healing-impairment action of nonsteroidal anti-inflammatory drugs, prescribed in patients with arthritis or osteoporosis. We produced ulcers in the antrum by administering BPPs to fasted rats, followed by refeeding, and confirmed their healing-impairment action on pre-existing gastric ulcers; the ulcerogenic effect is due to direct mucosal irritation and decrease in the mucosal anti-oxidative system, while the latter effect is due to dysregulation of growth factor expression, such as vascular endothelial growth factor and basic fibroblast growth factor, and angiogenesis in the ulcerated mucosa. In this article, we describe these two animal models for investigating BPP-related adverse reactions, including methods for the induction of antral ulcers and healing impairment of gastric ulcers, as well as measurement of pathogenic functional and biochemical changes. Curr. Protoc. Toxicol. 53:21.10.1-21.10.29. © 2012 by John Wiley & Sons, Inc.
- gastric adverse effect;
- antral ulceration;
- healing-impairment action