• MeSH
• autonomní nervový systém fyziologie   metabolismus   MeSH
• endotoxemie etiologie   komplikace   metabolismus   patofyziologie   MeSH
• kyselina askorbová * analýza   aplikace a dávkování   farmakologie   fyziologie   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy fyziologie   MeSH
• metabolický syndrom * komplikace   metabolismus   patofyziologie   MeSH
• oxidační stres fyziologie   MeSH
• vitamin E analýza   fyziologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The aim of our study was to investigate whether two potent anti-inflammatory agents, dexamethasone and anakinra, an IL-1 receptor antagonist, may influence acute kidney injury (AKI) and associated drug excretory functions during endotoxemia (LPS) in rats. Ten hours after LPS administration, untreated endotoxemic rats developed typical symptoms of AKI, with reduced GFR, impaired tubular excretion of urea and sodium, and decreased urinary excretion of azithromycin, an anionic substrate for multidrug resistance-transporting proteins. Administration of both immunosuppressants attenuated the inflammatory response, liver damage, AKI, and increased renal clearance of azithromycin mainly by restoration of GFR, without significant influence on its tubular secretion. The lack of such an effect was related to the differential effect of both agents on the renal expression of individual drug transporters. Only dexamethasone increased the urinary clearance of bile acids, in accordance with the reduction of the apical transporter (Asbt) for their tubular reabsorption. In summary, our data demonstrated the potency of both agents used for the prevention of AKI, imposed by endotoxins, and for the restoration of renal drug elimination, mainly by the improvement of GFR. The influence of both drugs on altered tubular functions and the expression of drug transporters was differential, emphasizing the necessity of knowledge of transporting pathways for individual drugs applied during sepsis. The effect of anakinra suggests a significant contribution of IL-1 signaling to the pathogenesis of LPS-induced AKI.

• MeSH
• akutní poškození ledvin etiologie   prevence a kontrola   MeSH
• antagonista receptoru pro interleukin 1 farmakologie   terapeutické užití   MeSH
• antibakteriální látky farmakokinetika   MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• azithromycin farmakokinetika   MeSH
• dexamethason farmakologie   terapeutické užití   MeSH
• eliminace ledvinami účinky léků   MeSH
• endotoxemie komplikace   farmakoterapie   MeSH
• endotoxiny farmakokinetika   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• imunosupresiva farmakologie   terapeutické užití   MeSH
• lipopolysacharidy MeSH
• potkani Wistar MeSH
• xenobiotika farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The purpose of the present study was to compare the activity of two different clinically available iron chelators on the development of acute liver injury after administration of the bacterial endotoxin (lipopolysaccharide [LPS]) in rats. Lipopolysaccharide was administered either alone or after pretreatment with dexrazoxane (DEX) or deferoxamine (DFO). Control groups received only saline or its combination with either chelator. After 8 h, untreated LPS rats developed liver injury, with signs of inflammation and oxidative stress. Lipopolysaccharide reduced plasma iron concentrations in association with increased production of hepcidin and the reduced liver expression of ferroportin. Administration of chelating agents to LPS animals showed distinct effects. Although both drugs were able to reduce liver iron content, together with corresponding changes in hepcidin and ferroportin expressions, only DFO showed a protective effect against liver injury despite relatively small liver concentrations. In sharp contrast, DEX failed to improve any hallmark of liver injury and even worsened the GSH/GSSG ratio, the indicator of oxidative stress in the tissue. High-performance liquid chromatography-mass spectrometry analysis showed marked liver accumulation of iron-chelating metabolite of DEX (ADR-925), whereas the parent compound was undetectable. Further downregulation of transporters involved in bile formation was observed after DFO in the LPS group as well as in healthy animals. Neither chelator imposed significant liver injury in healthy animals. In conclusion, we demonstrated marked differences in the modulation of endotoxemic liver impairment between two iron chelators, implicating that particular qualities of chelating agents may be of crucial importance.

• MeSH
• chelátory železa terapeutické užití   MeSH
• deferoxamin terapeutické užití   MeSH
• dexrazoxan terapeutické užití   MeSH
• endotoxemie komplikace   MeSH
• krysa rodu rattus MeSH
• nemoci jater farmakoterapie   etiologie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

OBJECTIVE: To determine the effect of Escherichia coli Nissle (Mutaflor, Ardeypharm GmbH, Herdecke, Germany) on the intestinal colonization, level of endotoxin and liver functions in patients with liver cirrhosis. METHODS: Thirty-nine patients with liver cirrhosis diagnosed by means of biopsy and clinical examinations were randomly allocated to treatment with E. coli Nissle or placebo for 42 days. Standard clinical examination, biochemical and hematological examinations, level of endotoxin and microbiological examination of the stool were performed before and after the treatment. RESULTS: In comparing the treatment of E. coli Nissle and placebo, significant improvement of the intestinal colonization (P<0.001) in the E. coli Nissle group was described. We found a trend of significant lowering of the endotoxemia (P=0.07) and improvement of liver functions evaluated by Child-Pugh score (P=0.06). CONCLUSION: E. coli Nissle seems to be effective in the restoration of normal colonic colonization and can probably lower endotoxemia in cirrhotic patients.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• endotoxemie komplikace   terapie   MeSH
• endotoxiny krev   MeSH
• Escherichia coli MeSH
• feces mikrobiologie   MeSH
• financování organizované MeSH
• jaterní cirhóza MeSH
• játra patofyziologie   MeSH
• kolon mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• probiotika terapeutické užití   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH