The Protective Effect of Nortriptyline Against Gastric Lesions Induced by Indomethacin and Cold-shock Stress in Rats

Background: Gastric ulcer is among the most serious stomach disorder universally. Several effective drugs are employed in the management of this disease, although there have been adverse effects in some cases. The aim of this study was to investigate the effect of nortriptyline to protect against gastric lesions, induced by indomethacin or cold-stress in rats. Methods: Gastric lesions were induced by oral indomethacin (30 mg/kg) or cold-shock at 2-4°C. Animals were pre-treated with 5, 10 or 20 mg/kg nortriptyline.  After 4hr of exposure to indomethacin or cold shock, the stomach was removed for histological examinations and the levels of enzymatic and non-enzymatic oxidative stress markers were determined in the tissue samples. Results: The results showed that nortriptyline at 20 mg/kg significantly restored the activity of the oxidative stress markers, such as superoxide dismutase (SOD) and catalase (CAT) enzymes. It also decreased the tissue malondialdehyde (MDA) concentration. In addition, nortriptyline at 20 mg/kg, ameliorated the gastric tissue damages caused by indomethacin or the cold shock. Conclusions: The results suggest that improvement in gastric mucosal lesions can be mediated by nortriptyline pretreatment, which is likely due to its antioxidant property.