A novel use of methylene blue as a pharmacological tool.
BACKGROUND
A new use of methylene blue as an ulcerogenic agent and the mechanisms involved were identified with an objective to exploit methylene blue as a pharmacological tool to study investigational antiulcer agents.


METHODS
Ulcerogenic potential was assessed using electron microscopy and measurement of an ulcer index after administering methylene blue (5-125 mg kg(-1), p.o.) or absolute ethanol (99%v/v, 2 ml, p.o.) to fasted rats. Estimation of thiobarbituric acid reactive substances, superoxide dismutase, reduced glutathione and catalase was used to assess oxidative stress. H(+)/K(+) ATPase activity, gastric mucosal blood flow and gastric acid secretion were measured to study the mechanism of methylene induced gastric ulcer.


RESULTS
Methylene blue (100 mg kg(-1), p.o.) produced marked ulceration of the gastric mucosa due to increased levels of thiobarbituric acid reactive substances, activities of the H(+)/K(+) ATPase and superoxide dismutase, and decreased blood flow to the gastric mucosa, activity of catalase combined with reduced glutathione levels.


CONCLUSIONS
It may be concluded that methylene blue activates the H(+)/K(+) ATPase to increase gastric acid secretion and reduces blood supply to gastric mucosa to produce oxidative stress that subsequently causes ulceration of gastric mucosa. Methylene blue can be used as an ulcerogenic agent to study mechanisms of investigational antiulcer agents.
Shah
Dhvanit I
DI
Department of Pharmacology, L. M. College of Pharmacy, Navrangpura, Ahmedabad-380009 Gujarat India. dhvanitshah@rediffmail.com
Santani
Dev D
DD
Goswami
Sunita S
SS
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D000431:Ethanol; D017506:H(+)-K(+)-Exchanging ATPase; D008751:Methylene Blue