Long‐Term Pretreatment With D‐Limonene Protects Gastric Lipid Composition by Reducing Oxidative Damage and Inflammation in Indomethacin‐Induced Gastric Injury

D‐Limonene is a monoterpene compound that is widely contained in citrus plants. It has been demonstrated to have several beneficial properties. The present study aimed to investigate the effect of D‐limonene against indomethacin‐induced gastric ulceration. D‐Limonene was administered orally for 21 days. Gastric ulceration was induced by oral administration of 25 mg/kg indomethacin via gastric gavage, five minutes after the administration of Lim or ranitidine. The stomachs of the rats were examined macroscopically and histopathologically to assess gastric lesions. GR, MDA, caspase‐3, TNF‐α, PGE 2 levels, and iNOS, catalase, and SOD activities were measured using the ELISA method. The lipid composition of gastric tissue was measured using a high‐performance thin‐layer chromatography method. The alteration observed in the lipid profile of the indomethacin group differed from that of the control group. In contrast, the lipid profile of the Lim‐treated groups was similar to that of the control group. Although the L50 group demonstrated a significant difference compared to the Ind group regarding GR, catalase, caspase‐3, and iNOS activity, no significant differences were observed in MDA, SOD, TNF‐α, and PGE 2 levels when compared to the Ind group. However, no indomethacin‐induced gastric damage was observed in the macroscopic and microscopic evaluations of gastric tissues collected from the L100 and L250 groups. Additionally, the gastroprotective activity of these two groups was noted in all tests. This study’s results indicated that a 50 mg/kg dose of D‐limonene was subeffective, while 100 and 250 mg/kg doses showed gastroprotective activity in rats.