Administration of indomethacin (250 mg/kg) to mice was followed by the formation of severe ulcerative and erosive injury to the gastric mucosa, inhibition of DNA synthesis, and development of oxidative stress. Fivefold pretreatment with sedatin (100 microg/kg) decreased the area of indomethacin-induced ulcers and erosions, stimulated DNA synthesis, and reduced the severity of oxidative stress. Non-arginine dermorphin analogue did not stimulate DNA synthesis and had no effect on the degree of oxidative stress. After pretreatment with L-NAME, sedatin did not modulate the synthesis of DNA under conditions of indomethacin-induced injury to the gastric mucosa.

We studied the effect of dalargin and its analogue [Dala]2-leu-enkephalin on the gastric mucosa in indomethacin-receiving animals. Indomethacin treatment was followed by severe injury to the gastric mucosa, decrease in proliferative activity of the epithelium, and stimulation of free-radical processes in gastric tissues. Dalargin significantly decreased the area of erosive and ulcerative lesions, had a normalizing effect on proliferation of epithelial cells, and reduced the degree of oxidative stress. Administration of [Dala]2-leu-enkephalin did not improve the state of the gastric mucosa.

Effects of angiotensin II, endothelin-1, dermorphin A 10 analogue, dalargin, and hydra peptide morphogen on DNA synthesis in duodenal smooth muscle cells of newborn albino rats were studied by 3H-thymidine autoradiography. Angiotensin II and endothelin-1 increased the number of DNA-synthesizing myocytes and did not affect the labeling intensity. Dermorphin A10 analogue, dalargin, and hydra peptide morphogen had no effect on these indexes. Key Words: regulatory peptides; DNA synthesis; smooth muscles; ontogenyOur previous experiments demonstrated that various regulatory peptides (RP) are involved in the establishment of tissue homeostasis during early ontogeny. RP modulate DNA synthesis in the epithelium [5] and myocardium [2,3] of newborn albino rats. These peptides affect proliferation of vascular smooth muscle cells [11]. However, the effects of RP on proliferation of visceral smooth muscle cells received little attention.Here we studied the effects of various RP on proliferation of duodenal smooth muscle cells in newborn albino rats. MATERIALS AND METHODSExperiments were performed on 217 newborn albino rats. Control and experimental groups were formed by the method of offspring separation to reduce genetically determined differences.Three groups of RP were studied: vasoactive peptides, opioid peptides, and hydra peptide morphogen (HPM). Angiotensin II and endothelin-1 (vasoactive peptides) were intraperitoneally injected in a daily dose of 5• -8 mol/kg body weight from the 2nd to the 6th day of life at 10.00 a.m. Control animals were

The intensity of proliferative processes (estimated from Ki-67 expression) and degree oxidative stress (chemiluminescence assay) in biopsy specimens from the terminal portion of the ileal mucosa were studied in patients with Crohn's disease. Crohn's disease is characterized by hyper-regenerative processes in the ileal mucosa. The labeling index (Ki-67 expression) in biopsy specimens from the intact ileal mucosa in patients with the irritable bowel syndrome (reference group) was 10.64±0.62%. The corresponding values in patients receiving monotherapy with mesalazine (group 1) and combination therapy with mesalazine and dalargin (group 2) were 24.05±1.17 and 22.90±0.92%, respectively. Analysis of free radical oxidation showed that this state is accompanied oxidative stress. Spontaneous and H(2)O(2)-induced luminol-dependent chemiluminescence in biopsy specimens from the ileal mucosa was 1.8-2.3-fold higher compared to the reference group. After therapy, the labeling index in groups 1 and 2 decreased to 18.60±1.18 and 14.38±0.81%, respectively. Histologically, normalization of the disease symptoms was more pronounced after combination therapy. The decrease in free radical oxidation in this group of patients was more pronounced than after mesalazine monotherapy. Our results suggest that oxidative stress plays a role in the hyper-regenerative reaction.

We studied the effect of simvastatin (24 mg/kg per os for 30 days) on DNA synthesis ((3)H-thymidine autoradiography) and free radical oxidation (chemiluminescent method) in the gastric mucosa of albino mice under normal conditions and in ulcerative process induced by single indometacin administration. Simvastatin treatment activated free radical oxidation, which was seen from enhanced chemiluminescence in the mucosa homogenate (by 1.7-4.6 times). Administration of indometacin against the background of simvastatin treatment potentiated local oxidative stress and inhibited DNA synthesis. Under these conditions, the area of ulcerative lesion in the gastric mucosa increased by 3.0 times.