Objective: To estimate the effects of teprenone on protecting gastric mucosa against steroids-induced damage.
Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 equal groups: normal control group, undergoing gastric infusion of normal saline for 7 days and fasting since the 4 th day for 4 days; model control group, undergoing gastric infusion of normal saline for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day for 4 days; low dose teprenone group, undergoing gastric infusion of teprenone 50 mg/kg for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day; middle dose teprenone group, undergoing gastric infusion of teprenone 50 mg/kg for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day; and high dose teprenone group, undergoing gastric infusion of teprenone 200 mg/kg for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day. Samples of gastric mucosa were taken out 24 hours after the last drug administration to calculate the ulcer index and observe the histological changes. Blood samples were collected from the abdominal cardinal vein. The levels of plasma ET-1 and prostaglandin E2 were examined by radioimmunoassay. Serum level of nitric oxide (NO) was determined by Griess method.
Results: In the model control group, the ulcer index, grade of histological lesions and ET-1 level increased significantly compared with the normal control group (44.5 vs. 0, 5.5 vs. 0, and 399 pg/ml +/- 74 pg/ml vs. 279 pg/ml +/- 56 pg/ml, all P < 0.01), the PGE(2) level decreased significantly. (154 pg/mg +/- 83 pg/mg vs 337 pg/mg +/- 112 pg/mg, P < 0.01), and the NO level did not changed significantly. In the 3 teprenone groups, the ulcer index decreased (32.5, 23.0, and 23.0 vs. 44.5, all P < 0.01), grade of histological lesions decreased (3.0, 3.0, and 1.5 vs. 5.5, all P < 0.01), ET-1 level decreased (299 pg/ml +/- 99 pg/ml, 284 pg/ml +/- 85 pg/ml, and 189 pg/ml +/- 32 pg/ml vs. 399 pg/ml +/- 74 pg/ml, P < 0.05, P < 0.01, and P < 0.01), the No level increased (56 micromol/L +/- 16 micromol/L, 62 micromol/L +/- 12 micromol/L, and 83 micromol/L +/- 9 micromol/L vs. 27 micromol/L +/- 5 micromol/L, all P < 0.01), and the PGE(2) level increased (190 pg/mg +/- 58 pg/mg, 196 pg/mg +/- 35 pg/mg, 241 pg/mg +/- 65 pg/mg vs. 154 pg/mg +/- 83 pg/mg, P > 0.05, P > 0.05, and P < 0.05) compared with the model control group.
Conclusion: Teprenone is a beneficial cytoprotective agent of gastric mucosa. Pretreatment with teprenone has gastroprotective effect against steroids-induced mucosal damage to a certain extent with a mechanism related to ET-1, NO, and PGE(2) concentrations in blood or gastric mucosa.