Fecal short-chain fatty acids at different time points after ceftriaxone administration in rats.

Short-chain fatty acids (SCFAs) are major products of the microbial fermentation of dietary fiber in the colon. Recent studies suggest that these products of microbial metabolism in the gut act as signaling molecules, influence host energy homeostasis and play major immunological roles. In the present study, defined the long-term effects of ceftriaxone administration on the fecal SCFAs concentration in Wistar rats. Ceftriaxone (300 mg/kg, i.m.) was administered daily for 14 days. Rats were euthanized in 1, 15 and 56 days after ceftriaxone withdrawal. Caecal weight and fecal concentration of SCFAs by gas chromatography were measured. Ceftriaxone administration induced time-dependent rats' caecal enlargement through accumulation of undigestable substances. In 1 day after ceftriaxone withdrawal, the concentrations of acetic, propionic, butyric acids and total SCFAs were decreased 2.9-, 13.8-, 8.5-, 4.8-fold (P < 0.05), respectively. Concentration of valeric, isovaleric and caproic acids was below the detectable level. That was accompanied by decreased 4.3-fold anaerobic index and increased the relative amount of acetic acid (P < 0.05). In 56 days, concentration of SCFAs was still below control value but higher than in 1 day (except propionic acid). Anaerobic index was lower 1.3-fold (P < 0.05) vs. control. Conclusion: antibiotic therapy induced long-term disturbance in colonic microbiota metabolic activity.

Carbohydrate composition of rat intestine surface mucus layer after ceftriaxone treatment.

The epidemiological studies have shown that antibiotic treatment increases the susceptibility to inflammatory bowel disease development. The disturbance of mucus layer integrity might be one of the possible mechanisms. The aim of the present study was to investigate the effect of antibiotic ceftriaxone treatment on glycoproteins level and its carbohydrate composition in surface mucus layer of rat intestine. The study was done on male Wistar rats (140-160 g). Ceftriaxone (300 mg/kg, i.m.) was administered once a day for 14 days. The surface mucus from terminal ileum and colon were collected on the 15th, 29th and 72nd days of the experiment. Total level of mucus glycoproteins, hexoses, hexosamines, fucose and sialic acids were measured. Ceftriaxone administration did not affect the levels of glycoproteins in rat ileum. In the colon, the levels of glycoprotein were 1.3-fold decreased (Р < 0.05) on the 72nd day of the experiment. These changes were accompanied by the 1.2-fold decrease of hexoses (Р < 0.05) and 3.1-fold (Р < 0.05) decrease of fucose level and 1.5-fold (Р < 0.05) increase of the levels of sialic acids in the surface mucus of the rat colon. Thus, ceftriaxone administration induces the long-term changes in the levels of glycoproteins and carbohydrates composition in the rat colon surface mucus. This could potentially explain the susceptibility to inflammatory bowel disea­ses development.

REDOX-SENSITIVE TRANSCRIPTION FACTORS EGR-1 AND SP1 IN THE PATHOGENESIS OF EXPERIMENTAL GASTRIC ULCER.

Changes in redox status of gastric mucosa cells are the main pathogenic factor of gastric erosion and gastric ulcer development. Pro-oxidants can affect cell transcription activity via changes in redox-sensitive transcription factors. Egr-1 and Sp-1 may regulate the transcription of genes that are associated with the pathogenesis of gastric ulcer (growthfactors, cell cycle regulators, etc.). The aim of the present study was to reveal the possible involvement of zinc-finger transcriptionfactors Egr-1 & Sp-1 in the molecular mechanisms underlying gastric lesions caused by aspirin administration and stress. Gastric ulcer was induced in male rats (180-220 g) by immobilization stress combined with water-immersion (IMO-WI) or aspirin gavage (10 mg/100 g). The rats were euthanized 20 min, 1 hour, or 3 hours following the ulcerogenic factor exposure. Protein expression was determined by Western blot analysis and RT-PCR; levels of SH-groups of proteins were determined by method of Ellman et al. Development of gastric ulcer lesions was associated with twofold (P < 0.05) decrease in concentration of protein SH-groups in the rat gastric mucosa. These changes were accompanied by significant (P < 0.05) increase in the expression of Egr-1 mRNA and protein in both gastric ulcer models, and the changes in IMO-WI were more profound. Increased levels of Egr-1 were associated with the decrease in SpI protein levels. We showed for the first time the competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 in the early phases of gastric ulcer development, which might facilitate inducible transcriptional activity of Egr-1 at the expense of reduction in Sp1 activity.

[NET WATER TRANSPORT VIA RAT COLON EPITELIUM UNDER THE EXPERIMENTAL DYSBIOSIS].

The aim of the present study was to investigate the effect of cephalosporin antibiotic ceftriaxone (50 mg/kg, i/m) and mac- rolide antibiotic azithromycin (15 mg/kg, per.os.) on net water transport across rat colonic epithelium. Study was done on male Wistar rats (180-250 g). Azithromycin or ceftriaxone was injected daily for 5 days. Net water transport was evaluated on the 6th day by isolated colonic loop perfusion technique in vivo on anaesthetized rats. Treatment with azithromycin increased 2,4-fold the absorption of water, while ceftriaxone caused decrease 1,9-fold water absorption. The antibiotics treatment within five days didn't change the composition of the fecal and colonic parietal microbiota. Azithromycin-induced increase in water absorption was associated with upregulation of AQP 8 water channel expression (P < 0.05) in colonic mucosa. Ceftriaxone treatment didn't change protein level of AQP8 but induced pro-inflammatory changes in colonic mucosa structure and mast cells degranulation. We showed for the first time the opposite effects ofmacrolide and cephalosporin antibiotics on net water transport across rat colonic epithelium.