From Stress to Secretagogues: Critical Appraisal of in-Vivo Ulcer Models

Abstract

Worldwide, peptic ulcer disease is considered a primary gastrointestinal disorder. Experimental models are based on several factors, including stress, chemical administration, vascular mechanisms, and neurotransmitter depletion. Stress models that simulate stressulcers are good for mimicking acute ulcer production but not for chronic ulcers. Chemical models, such as ethanol and acetic acid administration, are reproducible and easy to understand, but tend to be severe and exaggerated forms of injury or invasive methods of administration. These models, specifically those addressing vascular function and free radical generation, are effective for revealing the involvement of reactive oxygen species and for assessing antioxidants;however, the surgical demands are considerable. Histamine pellet and cysteamine administration focus on hypersecretion of acid and duodenal damage; therefore, they are useful models for drugs with anti-secretory and cytoprotective actions but do not model human disease very well. Reserpine models are useful for studying neurotransmitter deficiency and the vascular mechanisms of ulcer production, but again, more for acute ulcers. Together, these models have been used to evaluate a number of different agents, including antioxidants (quercetin, sinapic acid, N-acetylcysteine), anti-inflammatory agents (mesalazine, gabapentin, apocynin), and cytoprotective and vascular modulators (fluoxetine, tadalafil, fenchone). Although these methods do not perfectly represent human ulcerogenesis individually, they are complementary to one another and allow for a comprehensive analysis of novel therapeutic agents, as well as the assessment of oxidative stress, inflammation, vascular injury, and neurotransmitter depletion hypotheses of peptic ulcer disease.