Abstract

Anwar S.A, Sharif J.O, Yassat L.U and Dodi P.S

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 indomethacininduced 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.