The effect of quercetin on oxidative DNA damage and myelosuppression induced by etoposide in bone marrow cells of rats

There is increasing evidence for the existence of an association between the presence of etoposide phenoxyl radicals and the development of treatment-related acute myeloid leukemia (t-AML), which occurs in a few percent of patients treated with this chemotherapeutic agent. The most common side effect caused by etoposide is myelosuppression, which limits the use of this effective drug. The goal of the study was to investigate the influence of antioxidant querectin on myelosuppression and oxidative DNA damage caused by etoposide. The influence of quercetin and/or etoposide on oxidative DNA damage was investigated in LT-12 cell line and bone marrow cells of rats via comet assay. The effect of quercetin on myelosuppression induced by etoposide was invetsigated by cytological analysis of bone marrow smears stained with May-Grünwald-Giemsa stain. Etoposide caused a significant increase in oxidative DNA damage in bone marrow cells and LT-12 cell line in comparison to the appropriate controls. Quercetin significantly reduced the oxidative DNA damage caused by etoposide both in vitro and in vivo. Quercetin also significantly protected against a decrease in the percentage of myeloid precursors and erythroid nucleated cells caused by etoposide administration in comparison to the group treated with etoposide alone. The results of the study indicate that quercetin could be considered a protectively acting compound in bone marrow cells during etoposide therapy

The antioxidant quercetin protects HL-60 cells with high myeloperoxidase activity against pro-oxidative and apoptotic effects of etoposide

The protective action of quercetin against the pro-oxidant and apoptotic effect of etoposide was investigated in HL-60 cells with a high level of myeloperoxidase (MPO) activity and in cells treated with MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH). Quercetin significantly protected MPO-rich cells against the pro-oxidative (p<0.05) and apoptotic (p<0.05) effects of etoposide. Pre-treatment with ABAH abolished this protective influence of quercetin on apoptosis induced by etoposide but actually enhanced the action effect of quercetin against etoposide-generated reactive oxygen species (ROS) level by this cytostatic drug. Thus quercetin can protect HL-60 cells against the pro-oxidative activity of etoposide regardless of MPO activity

IN SEARCH OF HEDGES AND SAFE HAVENS IN GLOBAL FINANCIAL MARKETS

The aim of the paper is to search for hedges and safe havens within three instrument classes: assets (represented by the S&P500 index), gold and oil prices, and dollar exchange rates. Weekly series of returns of all the instruments from the period January 1995 – June 2015 are analysed. The study is based on conditional correlations between the instruments in different market regimes obtained with the use of copula-DCC GARCH models. It is assumed that different market regimes will be identified by statistical clustering techniques; however, only conditional variances (without conditional covariances) will be taken into account. The reason for this assumption is connected with the fact that variances can be understood as market risk, and, as such, are a good indicator of market conditions. A considerable advantage of such an approach is the lack of need to determine the number of market regimes, as it is established by clustering quality measures. What is more, the methodology used in the paper makes it possible to treat the relations between instruments symmetrically. The results obtained in the study reveal that only dollar exchange rates can be treated as a (strong) hedge and a (strong) safe haven for other instruments, while gold and oil are a hedge for assets

A dynamic analysis of causality between prices of corn, crude oil and ethanol

The objective of the paper is to analyse causality between prices of corn, crude oil and ethanol. The analysis conducted in this paper is a dynamic one, and the data used consist of weekly futures prices of crude oil, corn, and ethanol from January 5, 2007 till April 11, 2014. The assessment of causal links between prices of corn, crude oil and ethanol is carried out with the use of rolling regression applied to augmented-VAR framework proposed by Toda and Yamamoto (1995). The application of the rolling regression procedures into the modified Wald (MWALD) causality test allows for the investigation of the persistence of stability in causal relations between analysed prices. The results obtained indicate that the linkages between energy prices and agricultural commodity prices change in the period analysed. The results of Granger causality tests reveal that in the analysed period the price of corn influences the price of energy (crude oil and ethanol). Also crude oil prices influence corn prices and ethanol prices. However, the influence of ethanol prices on crude oil prices and corn prices has not been observed

The role of oxidative stress in the cooperation of parthenolide and etoposide in HL-60 cells

Background: 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. Methods: 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. Results: 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. Conclusions: 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

Curcumin exerts protective effects on the thyroid gland in propylthiouracil-treated rats

Introduction. Among the plant ingredients, some compounds interfere with the functions of the thyroid gland. However, there is limited research on the effect of curcumin (CMN) on the functions of this gland. The aim of this study was to analyze the effect of CMN on morphology, histochemical reactivity of cytochrome c oxidase (CCO) and secretion functions of the thyroid gland under conditions of hypothyroidism induced by propylthiouracil (PTU). Material and methods. The rats were treated for 30 days by gavage with CMN (100 mg/kg b.w.) and/or PTU (1 mg/kg b.w.). Control rats received vehicle only. Histomorphometric tests were performed on the thyroid glands, cytochrome c oxidase activity was visualized using the histochemical method, and the levels of thyroid hormones were measured using the radioimmunoassay method. Results. Rats receiving PTU showed compensatory changes in their thyroid glands, including a significant increase in thyroid epithelium height, a decrease in colloid volumen density, a decrease in the percentage of small follicles, an increase in medium-sized follicles compared to the control group, as well as a significant increase in CCO histochemical reactivity in the columnar epithelium and a decrease in FT4 serum level compared to the control group. The administration of CMN reversed these adverse changes caused by PTU. The PTU + CMN group exhibited a significant decrease in the height of the thyroid follicle epithelium compared to the PTU group. The percentage of small and medium-size follicles in the CMN + PTU group did not differ from the control group. Furthermore, CCO reactivity in the cubic epithelium and serum FT4 levels increased compared to the PTU group. Administration of CMN alone resulted in a significant increase in FT4 levels compared to the control group. Conclusions. The administration of CMN to rats with induced hypothyroidism resulted in a reduction of hyperplasia, hypertrophy, and increase in secretory activity of the thyroid gland. These findings suggest the protective effect of CMN against induced hypothyroidism

Volatility spillovers among uncertainty measures. The case of EU member states

The study investigates volatility spillovers among three types of uncertainty - financial, consumer, and industrial - in EU member states in the period between January 2005 and December 2017. The results suggest that most volatility is transmitted between countries within a given type of uncertainty. What is important, the pairs of countries that transmit uncertainty to one another are geographically related (i.e. they are neighbouring countries). Financial uncertainty can be seen as net volatility transmitter to both industrial and consumer uncertainties. The study proposes decomposition of the connectedness table into symmetric and skew-symmetric parts, which offers an attractive and comprehensive interpretation