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

Abstract:

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.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia

Degree grantor:

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

Promoter:

Elżbieta Wyska

Date issued:

2017

Identifier:

oai:dl.cm-uj.krakow.pl:4272

Call number:

ZB-129251

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Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

May 24, 2021

In our library since:

May 2, 2019

Number of object content hits:

1

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4273

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ZB-129251 May 24, 2021
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