OBJECTIVES: The therapeutic effect of probiotics has been studied in many clinical and experimental studies but no data exist concerning the influence of probiotics on pharmacokinetics of contemporary administered drugs. In this paper, we describe the influence of indomethacin-induced gastrointestinal lesions and Escherichia Coli Nissle 1917 medication on absorption of 5-aminosalicylic acid and its metabolite N-acetyl-5-aminosalicylic acid in rat. METHODS: 5-aminosalicylic acid (5-ASA) was given orally to rat using gastric probe as a suspension (25 mg/kg). The plasma time profiles of 5-ASA and its metabolite were compared between Group A (animals medicated with a suspension of Escherichia coli Nissle 1917 [EcN] in dose of 5 × 108 CFUs/day for 14 consecutive days), Group B (animals with indomethacin [IND]-induced gastrointestinal lesions; single dose of 25 mg/kg of IND), Group C (simultaneous administration of EcN and IND), and Group D (control animals without any medication). The blood samples for HPLC analysis has been taken from incannulated vena jugularis in time 30, 60, 90, 120, 180, 240, 360 min after 5-ASA administration to rat. RESULTS: The pharmacokinetics of 5-ASA was not significantly changed by EcN medication (Group A) in comparison to control animals (Group D). The significantly elevated absorption (AUC and cmax) of 5-ASA was found in animals with induced gastro-enteropathy with concurrently medicated with EcN (Group C) when compred to controls. In the case of metabolite N-acetyl-5-ASA, statistically no-significant differences were found between groups. CONCLUSIONS: Simultaneous probiotics (EcN) medication did not affect absorption 5-ASA from intestinal tract (the main site of ASAs action).
- MeSH
- absorpce MeSH
- antiflogistika nesteroidní škodlivé účinky farmakologie MeSH
- Escherichia coli fyziologie MeSH
- gastrointestinální nemoci chemicky indukované metabolismus MeSH
- gastrointestinální trakt účinky léků metabolismus MeSH
- indomethacin škodlivé účinky farmakologie MeSH
- kinetika MeSH
- krysa rodu Rattus MeSH
- mesalamin krev farmakokinetika MeSH
- osmolární koncentrace MeSH
- potkani Wistar MeSH
- probiotika farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- indomethacin MeSH
- mesalamin MeSH
AIM: To evaluate bacteriocinogeny in short-term high-dose indomethacin administration with or without probiotic Escherichia coli Nissle 1917 (EcN) in experimental pigs. METHODS: Twenty-four pigs entered the study: Group A (controls), Group B (probiotics alone), Group C (indomethacin alone) and Group D (probiotics and indomethacin). EcN (3.5×10(10) bacteria/d for 14 d) and/or indomethacin (15 mg/kg per day for 10 d) were administrated orally. Anal smears before and smears from the small and large intestine were taken from all animals. Bacteriocin production was determined with 6 different indicator strains; all strains were polymerase chain reaction tested for the presence of 29 individual bacteriocin-encoding determinants. RESULTS: The general microbiota profile was rather uniform in all animals but there was a broad diversity in coliform bacteria (parallel genotypes A, B1, B2 and D found). In total, 637 bacterial strains were tested, mostly Escherichia coli (E. coli). There was a higher incidence of non-E. coli strains among samples taken from the jejunum and ileum compared to that of the colon and rectum indicating predominance of E. coli strains in the large intestine. Bacteriocinogeny was found in 24/77 (31%) before and in 155/560 (28%) isolated bacteria at the end of the study. Altogether, 13 individual bacteriocin types (out of 29 tested) were identified among investigated strains. Incidence of four E. coli genotypes was equally distributed in all groups of E. coli strains, with majority of genotype A (ranging from 81% to 88%). The following types of bacteriocins were most commonly revealed: colicins Ia/Ib (44%), microcin V (18%), colicin E1 (16%) and microcin H47 (6%). There was a difference in bacteriocinogeny between control group A (52/149, 35%) and groups with treatment at the end of the study: B: 31/122 (25%, P=0.120); C: 43/155 (28%, P=0.222); D: 29/134 (22%, P=0.020). There was a significantly lower prevalence of colicin Ib, microcins H47 and V (probiotics group, P<0.001), colicin E1 and microcin H47 (indomethacin group, P<0.001) and microcins H47 and V (probiotics and indomethacin group, P=0.025) compared to controls. Escherichia fergusonii (E. fergusonii) was identified in 6 animals (6/11 isolates from the rectum). One strain was non-colicinogenic, while all other strains of E. fergusonii solely produced colicin E1. All animals started and remained methanogenic despite the fact that EcN is a substantial hydrogen producer. There was an increase in breath methane (after the treatment) in 5/6 pigs from the indomethacin group (C). CONCLUSION: EcN did not exert long-term liveability in the porcine intestine. All experimental pigs remained methanogenic. Indomethacin and EcN administered together might produce the worst impact on bacteriocinogeny.
- Klíčová slova
- Bacteriocinogeny, Escherichia coli Nissle 1917, Experimental pigs, Indomethacin,
- MeSH
- antiflogistika nesteroidní škodlivé účinky farmakologie MeSH
- bakteriociny metabolismus MeSH
- dechové testy MeSH
- Escherichia coli metabolismus MeSH
- indomethacin škodlivé účinky farmakologie MeSH
- lidé MeSH
- metagenom MeSH
- methan metabolismus MeSH
- probiotika farmakologie MeSH
- střevní sliznice účinky léků mikrobiologie MeSH
- Sus scrofa MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- bakteriociny MeSH
- indomethacin MeSH
- methan MeSH
- MeSH
- indomethacin škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- předčasná porodní činnost farmakoterapie MeSH
- těhotenství MeSH
- tokolytika škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- indomethacin MeSH
- tokolytika MeSH
Mechanical properties of the adult pulmonary vasculature are affected by perinatal experience of hypoxic pulmonary hypertension. In the present study, we followed the long-term effects of perinatal pulmonary hypertension induced by means other than hypoxia in rats. Daily injections of indomethacin (1 mg.kg-1 body weight (BW)) were given to the parturient rats. Their newborn pups had significantly increased number of muscularized peripheral pulmonary vessels. Pulmonary hypertension, however, did not persist to adulthood (mean pulmonary arterial pressure (Ppa) was 17.2 +/- 1.3 torr in the experimental group and 16.4 +/- 0.8 torr in controls). Pulmonary hypertension induced in adult rats by exposure to chronic hypoxia or by acute hypoxic challenges was similar in indomethacin-treated and control rats. Normoxic perfusion pressure/flow (P/Q) plots in isolated lungs were less steep in indomethacin-treated than in control rats. Acute hypoxia increased the slope of P/Q plots in indomethacin treated rats but not in controls. The described changes in the pulmonary vasculature induced by indomethacin are similar to those found previously in adult rats born in hypoxia. We conclude that perinatal pulmonary hypertension permanently modifies the pulmonary vasculature.
- MeSH
- arteria pulmonalis účinky léků embryologie MeSH
- časové faktory MeSH
- hypoxie komplikace MeSH
- indomethacin škodlivé účinky MeSH
- krysa rodu Rattus MeSH
- plíce účinky léků patofyziologie MeSH
- plicní hypertenze chemicky indukované patofyziologie MeSH
- plicní oběh účinky léků MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- venae pulmonales účinky léků embryologie MeSH
- zpožděný efekt prenatální expozice MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- indomethacin MeSH
Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.
- MeSH
- epidermální růstový faktor farmakologie MeSH
- ethanol škodlivé účinky MeSH
- gastriny krev MeSH
- indomethacin škodlivé účinky MeSH
- kapilární permeabilita účinky léků MeSH
- krysa rodu Rattus MeSH
- kyselina chlorovodíková metabolismus MeSH
- potkani Wistar MeSH
- slinné žlázy fyziologie MeSH
- žaludeční vředy chemicky indukované metabolismus MeSH
- žaludek krevní zásobení MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epidermální růstový faktor MeSH
- ethanol MeSH
- gastriny MeSH
- indomethacin MeSH
- kyselina chlorovodíková MeSH
- MeSH
- indomethacin škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- novorozenec MeSH
- plod účinky léků MeSH
- syndrom přetrvávajícího fetálního oběhu chemicky indukované diagnóza terapie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- indomethacin MeSH
- MeSH
- indomethacin škodlivé účinky analogy a deriváty terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- klinické zkoušky MeSH
- Názvy látek
- indomethacin MeSH
- VUFB 12018 MeSH Prohlížeč
- MeSH
- indomethacin škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- novorozenec MeSH
- otevřená tepenná dučej chemicky indukované MeSH
- předčasná porodní činnost prevence a kontrola MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- indomethacin MeSH
- MeSH
- dospělí MeSH
- indomethacin škodlivé účinky terapeutické užití MeSH
- kyčelní kloub MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci kloubů chemicky indukované MeSH
- osteoartróza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- indomethacin MeSH
- MeSH
- adrenalektomie škodlivé účinky MeSH
- fenylbutazon aplikace a dávkování škodlivé účinky MeSH
- histidindekarboxylasa metabolismus MeSH
- indomethacin aplikace a dávkování škodlivé účinky MeSH
- krysa rodu Rattus MeSH
- morčata MeSH
- myši MeSH
- peptický vřed chemicky indukované MeSH
- vagotomie škodlivé účinky MeSH
- žaludeční sliznice účinky léků MeSH
- žaludeční šťáva metabolismus MeSH
- žaludeční vředy chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- morčata MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- fenylbutazon MeSH
- histidindekarboxylasa MeSH
- indomethacin MeSH