IL-1 receptor blockade alleviates endotoxin-mediated impairment of renal drug excretory functions in rats
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25503728
DOI
10.1152/ajprenal.00266.2014
PII: ajprenal.00266.2014
Knihovny.cz E-zdroje
- Klíčová slova
- acute kidney injury, anakinra, dexamethasone, drug transporters, endotoxins,
- 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
- Názvy látek
- antagonista receptoru pro interleukin 1 MeSH
- antibakteriální látky MeSH
- antiflogistika MeSH
- azithromycin MeSH
- dexamethason MeSH
- endotoxiny MeSH
- imunosupresiva MeSH
- lipopolysacharidy MeSH
- xenobiotika 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.
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