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Abstract

B a c k g r o u n d: The aim of this study was to determine the effect of sesquiterpene lactone parthenolide on the cytotoxic and pro-oxidative effects of etoposide in HL-60 cells.
M e t h o d s: Cytotoxic effects were determined by incubation of HL-60 cells with various concentrations of examined compounds and combinations thereof, which were then stained with propidium iodide and analyzed using a flow cytometer. To determine the role of oxidative stress in the action of the compounds, co-incubation with N-acetyl-l-cysteine (NAC) and parthenolide and/or etoposide was used and the level of reduced glutathione (GSH) was detected.
R e s u l t s: Parthenolide significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide. However, in most cases of the combinations of parthenolide and etoposide, their effect was antagonistic, as confirmed by an analysis using the CalcuSyn program. The examined compounds significantly reduced the level of GSH in HL-60 cells. Combination of etoposide at a concentration of 1.2 μM and parthenolide also significantly reduced GSH level. However, in the case of a combination of etoposide at a concentration of 2.5 μM with parthenolide, a significant increase in the level of GSH was obtained compared to compounds acting alone. This last observation seems to confirm the antagonism between the compounds tested.
C o n c l u s i o n s: Parthenolide did not limit the cytotoxic effect of etoposide in HL-60 cells even in the case of antagonistic interaction. If parthenolide does increase GSH levels in combination with etoposide in the normal hematopoietic cells, it could protect them against the pro-oxidative effects of this anti-cancer drug.
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Authors and Affiliations

Monika A. Papież
1
Oliwia Siodłak
1
Wirginia Krzyściak
2

  1. Department of Cytobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
  2. Department of Medical Diagnostic, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
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Abstract

I n t r o d u c t i o n: Interactions between oral microbiota and systemic diseases have been suggested. We aimed to examine the composition of oral microbiota with reference to antioxidative defense and its correlation with clinical state in Crohn’s disease (CD) in comparison to ulcerative colitis (UC).

Ma t e r i a l s a n d Me t h o d s: Smears were taken from the buccal and tongue mucosa of patients with CD, UC and controls, and cultured with classical microbiology methods. Bacterial colonies were identified using matrix-assisted laser desorption/ionization (MALDI) with a time-of-flight analyzer (TOF). Blood morphology and C-reactive protein (CRP) were analyzed in the hospital laboratory. Antioxidative defense potential (FRAP) was determined using spectrophotometry in saliva and serum.

R e s u l t s: Oral microbiota in CD patients were characterized by lower diversity in terms of the isolated bacteria species compared to UC and this correlated with reduced FRAP in the oral cavity and intensified systemic infl ammation. Oral microbiota composition in CD did not depend on the applied treatment. In CD patients, a negative correlation was observed between the FRAP value in saliva and serum and the CRP value in serum. Individual differences in the composition of oral microbiota suggest that different bacteria species may be involved in the induction of oxidative stress associated with a weakening of antioxidative defense in the oral cavity, manifested by ongoing systemic inflammation.

C o n c l u s i o n s: Analysis of both the state of the microbiota and antioxidative defense of the oral cavity, as well as their referencing to systemic inflammation may potentially prove helpful in routine diagnostic applications and in aiding a better understanding of CD and UC pathogenesis associated with oral microbiota.

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Authors and Affiliations

Katarzyna Szczeklik
Danuta Owczarek
Dorota Cibor
Marta Cześnikiewicz-Guzik
Paweł Krzyściak
Agnieszka Krawczyk
Tomasz Mach
Elżbieta Karczewska
Wirginia Krzyściak
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Abstract

Oxidative stress (OxS) has been implicated in the pathogenesis of Crohn’s disease (CD). The aim of this study was to examine whether nonenzymatic antioxidants are associated with active CD, by using the FRAP and GSH assay in plasma. Additionally, we measured bilirubin and albumin levels as two individual components of the plasma antioxidant system. A total of 55 patients with established CD, 30 with active CD and 25 with inactive disease, and 25 healthy individuals were prospectively enrolled in this study. We evaluated CD activity index, BMI and blood morphology, platelet count, serum CRP level, and bochemical parameters of OxS: ferric reducing ability of plasma (FRAP), reduced glutathione (GSH) in plasma and bilirubin and albumin levels in serum. Plasma FRAP and GSH concentrations were decreased in both CD groups compared to controls and negatively correlated with CDAI values (FRAP: r = –0.572, p = 0.003; GSH: r = –0.761, p = 0.001), CRP and platelet count. Bilirubin and albumin levels were lower in the serum of active CD patients than inactive CD patients and controls and negatively correlated with the CD activity index (r = –0328, p = 0.036, r = –0.518, p = 0.002) and CRP (r = –0.433, p = 0.002). The decreased FRAP and GSH levels in plasma and bilirubin and albumin levels in serum of patients with active CD compared to inactive CD and controls underlines the importance of OxS in the pathophysiology and activity of CD.

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Authors and Affiliations

Katarzyna Szczeklik
Wirginia Krzyściak
Dorota Cibor
Kamil Kozioł
Halina Pocztar
Jolanta Pytko-Polończyk
Tomasz Mach
Danuta Owczarek

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