Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease.
Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models. This study evaluates ulcer index, hexosamine content, microvascular permeability, and gastric content in three acute stress models (cold-restraint, restraint, and water immersion restraint). Macroscopic pictures of the ulcerogenic stomach explain that in contrast to other models, cold-restraint stress (CRS) exposure produced marked ulcers on the fundic area of the stomach. Results of the present study depicted that each stress model significantly increased ulcer index, microvascular permeability and decreased hexosamine level, however, the maximum in the case of CRS-exposed rats. Total acidity and pH of the gastric content remains unchanged in all the stress models. On the contrary, the gastric volume significantly decreased only in case of CRS, while unchanged in other stress models. The overall results revealed that the CRS resembles the pathophysiology of SRMD closely. It is the best and feasible model among all the models to evaluate drugs for the treatment of SRMD.
Department of Pharmacology, L. J. Institute of Pharmacy.
Bhagawati
B
Saxena
Division of Pharmacology and Toxicology, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University).
Sanjay
S
Singh
D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D003080:Cold Temperature; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism / Q000503:physiopathology; D006595:Hexosamines / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007101:Immersion; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000378:metabolism / Q000503:physiopathology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*
D006595:Hexosamines
Mucosal barrier; cold-restraint stress; gastric mucosal blood flow; microvascular permeability; restraint stress; water immersion restraint stress