An investigation into the gastro-protective effects of certain antidepressants in relation to ranitidine on indomethacin-induced ulcer in depressed rats

Abstract

The study investigated the gastro-protective effects of certain antidepressants in relation to ranitidine 
on indomethacin-induced ulcer in depressed rats. Animals were divided into 6 groups (n = 8). Induction 
of depression was done by clonidine (0.8 mg/kg; i.p.) for 10 days in all groups except the 1st one 
(normal control). Depressive-like behavior was confirmed by increased immobility time in forced 
swimming test. Groups 1 and 2 received saline (normal and depressed controls, respectively). Groups 3 
to 6 received p.o. mirtazapine (10 mg/kg), escitalopram (10 mg/kg), venlafaxine (20 mg/kg) and ranitidine 
(50 mg/kg), respectively for 30 days. After the last treatment, gastric ulcer was induced using 
indomethacin (25 mg/kg; p.o.) in groups 2 to 6. An additional group received indomethacin alone 
(control indomethacin). Animals were sacrificed and ulcer scores were determined. Part of the stomach 
was preserved for histopathologic studies while the other part was used for determination of reduced 
glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and 
interleukin-10 (IL-10) contents. Pretreatment with all antidepressants used ameliorated indomethacin
induced changes in rat stomach. Biochemical findings were supported by histologic studies. In 
conclusion, the observed gastroprotective effects of mirtazapine, escitalopram and venlafaxine are 
possibly mediated by modulation of inflammatory cytokines and antioxidant effects.