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Title: Effect of caspase inhibitor on the efficacy of selected anti-inflammatory drugs in experimental model of sepsis in mice


Results of clinical studies and animal experiments of recent years support the hypothesis of increased apoptosis in lymphoid tissues in sepsis. Main goal of this study was to evaluate the effectiveness of concomitant administration of selected anti-inflammatory agents (bupropion, lisofylline, prednisolone) with a nonselective caspase inhibitor (Z-VAD-FMK) in animal model of sepsis. Moreover, a pharmacokinetic study of Z-VAD-FMK was performed. The effectiveness of tested compounds was evaluated by the measurement of markers of apoptosis, necrosis, inflammation and oxidative stress. Moreover, survival tests were carried out by the Kaplan-Meier method. Concentrations of Z-VAD-FMK and its active metabolite were measured in serum and tissues by LC MS/MS method. The results of this study indicate that apoptosis, necrosis of thymocytes and expression of IL-6 in liver of mice with experimental sepsis were most effectively inhibited after concomitant administration of Z-VAD-FMK and bupropion. Moreover, co-administration of the caspase inhibitor limited a proapoptotic potential of prednisolone in thymus. Z-VAD-FMK administered intravenously to mice is extensively metabolized to its acid derivative, which may suggest that in vivo this caspase inhibitor acts by its active metabolite. Z-VAD-FMK is rapidly distributed to tissues and reaches the highest concentrations in intestines and stomach, whereas its metabolite in intestines and liver.

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2 - studia doktoranckie

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Uniwersytet Jagielloński. Collegium Medicum w Krakowie. Zakład Farmakokinetyki i Farmacji Fizycznej.


Elżbieta Wyska

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tylko w bibliotece

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Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

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Last modified:

May 24, 2021

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May 2, 2019

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Edition name Date
ZB-129251 May 24, 2021


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