fumarates and Stomach-Ulcer

Results of the very first experiments conducted to evaluate therapeutic potentials of a fumarate containing Fumaria indica extract and of fairly low daily oral doses of monomethyl fumarate for prevention of chronic unavoidable foot-shock stress-induced gastric ulcers, and possible involvement of diverse neuro-hormonal and oxidative process in their stress response desensitizing effects are reported and discussed in this article. Preventive effects of 21 daily oral 60, 120, and 240 mg/kg doses of a standardized 50 % methanolic F. indica extract (MFI) and 1.25, 2.50, and 5.00 mg/kg/day of pure monomethyl fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, adrenal and spleen weights, gastric ulcer and ulcer index, weight of glandular stomach, protective mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach fundus, and brain tissues of male rats were quantified. Other parameters quantified were plasma corticosterone levels, brain monoamine levels, and expressions of the cytokines TNF-α, IL-10, and IL-1β in blood and brain of stressed and treated rats. Most but not every observed stress-induced anomalies were suppressed or completely prevented by both MFI and pure MMF treatments in dose-dependent manner. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both MFI and MMF are potent gastro-protective agents against chronic unavoidable stress-induced ulcers and strongly suggest that they act as regulators or modulators of monoamine, corticosterone, and cytokine homeostasis.

Topics: Animals; Body Weight; Brain; Chronic Disease; Corticosterone; Cytokines; Fumarates; Fumaria; Male; Maleates; Methanol; Organ Size; Plant Extracts; Protective Agents; Rats; Real-Time Polymerase Chain Reaction; Stomach; Stomach Ulcer; Stress, Psychological

Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model.. Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats.. Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model.. Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.

Topics: Amides; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cytokines; Dinoprostone; Fumarates; Glutathione; Hydrogen-Ion Concentration; Indomethacin; Kinetics; Male; Malondialdehyde; Models, Biological; Oxidative Stress; Rats, Wistar; Renin-Angiotensin System; RNA, Messenger; Stomach; Stomach Ulcer; Superoxide Dismutase

Topics: Adult; Cycloheptanes; Duodenal Ulcer; Female; Fumarates; Humans; Male; Middle Aged; Parasympatholytics; Stomach Ulcer

Topics: Animals; Fumarates; Male; Rats; Stomach Ulcer

Topics: Acids; Arthritis; Arthritis, Rheumatoid; Breast Neoplasms; Chromatography; Citric Acid Cycle; Female; Fumarates; Glutarates; Histocytochemistry; Hodgkin Disease; Humans; Neoplasms; Osteosarcoma; Rectal Neoplasms; Sarcoma; Stomach Neoplasms; Stomach Ulcer; Succinates; Thyroid Neoplasms; Uric Acid; Urine; Uterine Cervical Neoplasms; Uterine Neoplasms