Effect of HMG-CoA-reductase inhibitor on DNA synthesis and free radical oxidation in the gastric mucosa under normal conditions and during indometacin-induced ulcerative process in the stomach of albino mice.

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.

Intensity of proliferative processes and degree of oxidative stress in the mucosa of the ileum in Crohn's disease.

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.

Protective effect of dermorphin analogue sedatin on indomethacin-induced injury to the gastric mucosa.

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.

Effect of histochrome on the severity of delayed effects of prenatal exposure to lead nitrate in the rat brain.

The effects of histochrome on the severity of delayed effects of prenatal exposure to lead nitrate were studied in the rat brain. Exposure of pregnant rats to lead nitrate during activation of free radical oxidation reduced activity of NADH- and NADPH-dehydrogenases in cortical neurons of their 40-day-old progeny, reduced the number of neurons in a visual field, increased the number of pathologically modified neurons, and stimulated rat motor activity in an elevated plus-maze. Two intraperitoneal injections of histochrome in a dose of 0.1 mg/kg before and after lead citrate challenge attenuated the manifestations of oxidative stress and prevented the changes in some morphological and histochemical parameters of the brain, developing under the effect of lead exposure.

Mechanisms for the effect of arginine-containing dermorphin analogue on proliferative processes in the gastric mucosa of albino rats.

Treatment with synthetic arginine-containing dermorphin analogue sedatin (100 mg/kg, 5 intraperitoneal injections) stimulated DNA synthesis in the gastric mucosa and decreased spontaneous and induced chemiluminescence in homogenates of the stomach from albino rats. Non-arginine sedatin analogue in the same dose had little effect on DNA synthesis and free radical oxidation. Fivefold treatment with NO synthase inhibitor L-NAME (9.3 x 10(-5) mol/kg) suppressed DNA synthesis in the gastric mucosa. Sedatin did not modulate DNA synthesis against the background of L-NAME administration.

Effect of dalargin on DNA synthesis in the gastric mucosa of albino rats.

3H-thymidine autoradiography and chemiluminescence study demonstrated pronounced effect of dalargin on the state of the gastric mucosa in albino rats. Dalargin stimulated DNA synthesis in the epithelium of the gastric mucosa and increased buffer capacity of its antiradical and antioxidant systems. Dalargin analogue not containing arginine ([D-Ala2]-leu-enkephalin) had little effect on these parameters. NO synthase inhibitor L-NAME abolished the effects of dalargin on DNA synthesis in the gastric mucosa. Our results suggest that the NO system plays an important role in the effect of dalargin on the gastric mucosa.