Effect of Leu-Ile-Lys tripeptide on the activity of free radical oxidation and expression of сyclooxygenase-1 and -2 in gastric mucosa in experimental indomethacin-induced ulcer in rats

Abstract

Aim. To determine the effect of Leu-Ile-Lys tripeptide on indicators of oxidative stress and expression of cyclooxygenase-1 and -2 in the gastric mucosa on the background of experimental indomethacin-induced ulcer. 
 Methods. Experiments were performed on 35 male Wistar rats with a body mass of 200-250 g aged 2-3 months that were divided into 3 groups: the control group (intact rats, 8 animals), control group (simulation of indomethacin-induced gastropathy, 12 animals) experimental group (simulation of indomethacin-induced gastropathy + administration of Leu-Ile-Lys tripeptide, 15 animals). The tripeptide Leu-Ile-Lys obtained by chemical synthesis (sample purity at least 98%) was administered intragastrically daily for 7 days before the simulation of indomethacin-induced damage of the gastric mucosa in a dose of 11.5 mg/kg. The model of indomethacin-induced damage to the rodent gastric mucosa was reproduced by a single intragastric administration of indomethacin in a dose of 60 mg/kg in 1 ml of saline. In the stomach homogenate the activity of free radical oxidation was determined by conventional methods. For quantitative determination of cyclooxygenase-1, -2 in gastric homogenate the method of enzyme immunoassay was used. The concentration was determined spectrometrically by the color intensity of the samples. 
 Results. With a prophylactic administration of tripeptide Leu-Ile-Lys, concentration of tiobarbiturate-reactive products was normalized, total antioxidant activity increased and the activity of antioxidant enzymes decreased compared to the control group. The concentration of cyclooxygenase-2 in gastric homogenate from the experimental animals was 2.3 times lower than that of the control rats. 
 Conclusion. Use of Leu-Ile-Lys tripeptide in experimental indomethacin-induced gastric ulcer showed a significant decrease of oxidative damage and inflammation in the gastric mucosa.