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Title: The assessment of eicosanoid profile in animal models of endothelial dysfunction

Abstract:

In this study, two original bioanalytical methods for quantification of eicosanoids biosynthesised from arachidonic acid (AA) via different metabolic pathways were developed and validated using UPLC-MS/MS technique. The methods allowed to assess the eicosanoid profile in selected animal models of endothelial dysfunction and its changes upon pharmacological modulation of vascular function.In NO-deficient mice, the biosynthesis of eicosanoids formed by cyclooxygenase (COX) was elevated. MNA treatment improved the vessel function by activation of COX-independent mechanisms.In murine model of hypertension, angiotensin II infusion increased the biosynthesis of CYP450- derived 20-HETE. The inhibition of thrombin activity by dabigatran improved the function of endothelium by sustaining the NO bioavailability and reducing the 20-HETE production.The development of 4T1 breast cancer was associated with the elevated biosynthesis of eicosanoids formed by COX and lipoxygenase (LOX) and with the reduced production of CYP450-derived AA metabolites. The inhibition of NO synthase increased the biosynthesis of epoxyeicosatrienoic acids (EET) and 20-HETE, which probably supported the disease progression under NO-deficiency.The obtained results show the heterogeneity of eicosanoid profile in investigated murine models of endothelial dysfunction and the pharmacological modulation of vascular function indicates which AA metabolic pathways could be an effective target in the treatment of hypertension and breast cancer.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Farmaceutyczny.

Promoter:

Maria Walczak ; Kamil Kuś

Date issued:

2019

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:4381

Call number:

ZB-131048

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

Oct 7, 2020

In our library since:

Oct 7, 2020

Number of object content hits:

1

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4382

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ZB-131048 Oct 7, 2020
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