fluvoxamine and Gastrointestinal-Hemorrhage

Topics: Aged; Antidepressive Agents; Aryl Hydrocarbon Hydroxylases; Aspirin; Clopidogrel; Comorbidity; Cytochrome P-450 CYP2C19; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Early Diagnosis; Fluoxetine; Fluvoxamine; Gastrointestinal Hemorrhage; Genotype; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Selective Serotonin Reuptake Inhibitors; Ticlopidine

Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Disease Models, Animal; Fluvoxamine; Gastrointestinal Hemorrhage; HSP70 Heat-Shock Proteins; Indomethacin; Male; Mice; Mice, Inbred ICR; Restraint, Physical; Selective Serotonin Reuptake Inhibitors; Stomach Ulcer; Stress, Psychological

Topics: Adult; Ecchymosis; Epistaxis; Fluvoxamine; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Male; Purpura; Selective Serotonin Reuptake Inhibitors