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Phenols and their derivatives commonly exist in the environment. These compounds are used as the components of dyes, polymers, drugs and other organic substances. The presence of phenols in the ecosystems is also related with production and degradation of numerous pesticides and the generation of industrial and municipal sewages. Some phenols are also formed during natural processes. These compounds may be substituted with chlorine atoms, may be nitrated, methylated or alkylated, both phenols and catechols are harmful ecotoxins. Toxic action of these compounds stems from unspecified toxicity related to hydrophobocity and also to the generation of organic radicals and reactive oxygen species. Phenols and catechols reveal peroxidative capacity, they are hematotoxic and hepatotoxic, provoke mutagenesis and carcinogenesis toward humans and other living organisms. [ABSTRACT FROM AUTHOR]

The effectiveness of penetration of erythrocyte membrane by sodium salt of 2,4-dichlorophenoxyacetic acid was analyzed. The experiment was executed in a dependence on different doses of the herbicide and at different times of incubation of red blood cells with 2,4-D-Na. It is known that the main mechanism of detoxification of the cell from xenobiotics including 2,4-D is to bind them with proteins contained in blood plasma. In the case of exposure of blood to high doses of 2,4-D-Na, the unbound part of xenobiotics may penetrate into erythrocytes and change the activity of numerous parameters of the cells. The results obtained by the use of high pressure liquid chromatography (HPLC) revealed that 2,4-D-Na is adsorbed by erythrocytes of 5% haematocrite in the amount of ∼1% of the initial concentration. Moreover, it was observed that 2,4-D-Na is capable of accumulating in erythrocyte's membrane and haemolysate in the amounts of 0.15% and 1.23% of the initial concentration, respectively. It was also stated that penetration of 2,4-dichlorophenoxyacetic acid into erythrocytes is not associated with incubation time (the similar concentrations of 2,4-D-Na were detected after different incubation times of 0.5 to 3 hours); however, it was related with concentrations of the herbicide. We suggest that 2,4-D-Na was transported with concentration gradient in human erythrocytes. [ABSTRACT FROM AUTHOR]

Particles of various types of plastics, including polystyrene nanoparticles (PS-NPs), have been determined in human blood, placenta, and lungs. These findings suggest a potential detrimental effect of PS-NPs on bloodstream cells. The purpose of this study was to assess the mechanism underlying PS-NPs-induced apoptosis in human peripheral blood mononuclear cells (PBMCs). Non-functionalized PS-NPs of three diameters: 29 nm, 44 nm, and 72 nm were studied used in this research. PBMCs were isolated from human leukocyte-platelet buffy coat and treated with PS-NPs at concentrations ranging from 0.001 to 200 μg/mL for 24 h. Apoptotic mechanism of action was evaluated by determining the level of cytosolic calcium ions, as well as mitochondrial transmembrane potential, and ATP levels. Furthermore, detection of caspase-8, -9, and -3 activation, as well as mTOR level was conducted. The presence of apoptotic PBMCs was confirmed by the method of double staining of the cells with propidium iodide and FITC-conjugated Annexin V. We found that all tested NPs increased calcium ion and depleted mitochondrial transmembrane potential levels. The tested NPs also activated caspase-9 and caspase-3, and the smallest NPs of 29 nm of diameter also activated caspase-8. The results clearly showed that apoptotic changes and an increase of mTOR level depended on the size of the tested NPs, while the smallest particles caused the greatest alterations. PS-NPs of 26 nm of diameter activated the extrinsic pathway (increased caspase-8 activity), as well as intrinsic (mitochondrial) pathway (increased caspase-9 activity, raised calcium ion level, and decreased transmembrane mitochondrial potential) of apoptosis. All PS-NPs increased mTOR level at the concentrations smaller than those that induced apoptosis and its level returned to control value when the process of apoptosis escalated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glyphosate in the concentrations corresponding to environmental or occupational exposure has been shown to induce epigenetic changes potentially involved in carcinogenesis. This substance (1) changes the global methylation in various cell types and organisms and is responsible for the methylation of different promoters of individual genes, such as TP53 and P21 in human PBMCs, (2) decreases H3K27me3 methylation and H3 acetylation and increases H3K9 methylation and H4 acetylation in rats, (3) increases the expression of P16, P21, CCND1 in human PBMCs, and the expression of EGR1, JUN, FOS, and MYC in HEK293 cells, but decreases TP53 expression in human PBMCs, (4) changes the expression of genes DNMT1, HDAC3, TET1, TET2, TET3 involved in chromatin architecture, e.g. in fish Japanese medaka, (5) alters the expression of various small, single-stranded, non-coding RNA molecules engaged in post-transcriptional regulation of gene expression, such as miRNA 182-5p in MCF10A cells, miR-30 and miR-10 in mammalian stem cells, as well as several dozen of murine miRNAs. Epigenetic changes caused by glyphosate can persist over time and can be passed on to the offsprings in the next generation; in the third generation they can result in some disorders development, such as prostate disease or obesity. Some epigenetic mechanisms have indicated a potential risk of breast cancer development in human as a result of the exposure to glyphosate. It should be emphasized that the majority of reported epigenetic changes have not yet been associated with the final metabolic effects, which may depend on many other factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Iron deficiency (ID) and iron status in non-anemic patients with atherosclerotic cardiovascular disease (ASCVD) risk without a history of cardiovascular diseases is still weakly explored. In this study, the authors evaluated the most common ID definitions in this group of patients. A total of 533 participants from the National Health and Nutrition Examination Survey (NHANES) were collected from 2005-2006, 2017-2018, and 2017-2020 records. Participants were divided according to their ASCVD risk score to the following groups: low (n=168, 32%), borderline (n=43, 8%), intermediate (n=200, 37%), and high (n=122, 23%). There was a higher prevalence of ID in low- and borderline-risk groups in contrast to intermediate- and high-risk groups. Higher serum ferritin concentrations were observed in groups with a greater ASCVD risk score. Transferrin saturation (TSAT) was comparable in all ASCVD categories. Lack of ID, defined by three different guidelines that are mainly based on serum ferritin levels, predisposed to a higher ASCVD risk category. Normal iron status, defined by these three guidelines, was positively associated with the male gender. The opposite association was observed for non-Hispanic Whites. The analyzed criteria of ID, based mostly on serum ferritin levels, demonstrated limited usefulness in patients with increased ASCVD risk. Further studies should be done to determine proper ID diagnostic criteria in non-anemic patients without a previous cardiovascular history with elevated ASCVD risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Skrzypczak et al.)

Background: Tetrabromobisphenol A (TBBPA) is the most commonly used brominated flame retardant (BFR) in the industry. TBBPA has been determined in environmental samples, food, tap water, dust as well as outdoor and indoor air and in the human body. Studies have also shown the toxic potential of this substance. In search of a better and less toxic BFR, tetrabromobisphenol S (TBBPS) has been developed in order to replace TBBPA in the industry. There is a lack of data on the toxic effects of TBBPS, while no study has explored apoptotic mechanism of action of TBBPA and TBBPS in human leukocytes., Methods: The cells were separated from leucocyte-platelet buffy coat and were incubated with studied compounds in concentrations ranging from 0.01 to 50 µg/mL for 24 h. In order to explore the apoptotic mechanism of action of tested BFRs, phosphatidylserine externalization at cellular membrane (the number of apoptotic cells), cytosolic calcium ion and transmembrane mitochondrial potential levels, caspase-8, -9 and -3 activation, as well as PARP-1 cleavage, DNA fragmentation and chromatin condensation in PBMCs were determined., Results: TBBPA and TBBPS triggered apoptosis in human PBMCs as they changed all tested parameters in the incubated cells. It was also observed that the mitochondrial pathway was mainly involved in the apoptotic action of studied compounds., Conclusions: It was found that TBBPS, and more strongly TBBPA, triggered apoptosis in human PBMCs. Generally, the mitochondrial pathway was involved in the apoptotic action of tested compounds; nevertheless, TBBPS more strongly than TBBPA caused intrinsic pathway activation.

(1) Background: 2,4,6-Tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) are utilized as brominated flame retardants (BFRs) in order to reduce the combustion of materials used in various utility products. The presence of 2,4,6-TBP and PBP has been reported in environmental samples as well as in inhaled air, dust, food, drinking water, and the human body. To date, there are limited data concerning the toxic action of 2,4,6-TBP and particularly PBP, and no study has been conducted to assess the apoptotic mechanism of action of these substances in human leukocytes. (2) Methods: PBMCs were isolated from leukocyte-platelet buffy coat and treated with tested substances in concentrations ranging from 0.01 to 50 µg/mL for 24 h. The apoptotic mechanism of action of the tested BFRs was assessed by the determination of phosphatidylserine exposure on the PBMCs surface, the evaluation of mitochondrial potential and cytosolic calcium ion levels, and the determination of caspase-8, -9, and -3 activation. Moreover, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, DNA fragmentation, and chromatin condensation were analyzed. (3) Results: 2,4,6-TBP and, more strongly, PBP induced apoptosis in PBMCs, changing all tested parameters. It was also found that the mitochondrial pathway was mainly involved in the apoptosis of PBMCs exposed to the studied compounds. (4) Conclusions: 2,4,6-TBP and PBP triggered apoptosis in human PBMCs, and some observed changes occurred at 2,4,6-TBP concentrations that were detected in humans occupationally exposed to this substance.

Benzo[ a ]pyrene (B[ a ]P) is the main representative of polycyclic aromatic hydrocarbons (PAHs), and has been repeatedly found in the air, surface water, soil, and sediments. It is present in cigarette smoke as well as in food products, especially when smoked and grilled. Human exposure to B[ a ]P is therefore common. Research shows growing evidence concerning toxic effects induced by this substance. This xenobiotic is metabolized by cytochrome P450 (CYP P450) to carcinogenic metabolite: 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene (BPDE), which creates DNA adducts, causing mutations and malignant transformations. Moreover, B[ a ]P is epigenotoxic, neurotoxic, and teratogenic, and exhibits pro-oxidative potential and causes impairment of animals' fertility. CYP P450 is strongly involved in B[ a ]P metabolism, and it is simultaneously expressed as a result of the association of B[ a ]P with aromatic hydrocarbon receptor (AhR), playing an essential role in the cancerogenic potential of various xenobiotics. In turn, polymorphism of CYP P450 genes determines the sensitivity of the organism to B[ a ]P. It was also observed that B[ a ]P facilitates the multiplication of viruses, which may be an additional problem with the widespread COVID-19 pandemic. Based on publications mainly from 2017 to 2022, this paper presents the occurrence of B[ a ]P in various environmental compartments and human surroundings, shows the exposure of humans to this substance, and describes the mechanisms of its toxicity.

Bromophenolic flame retardants (BFRs) are a large group of synthetic substances used in the industry in order to reduce the flammability of synthetic materials used in electrical and electronic devices, textiles, furniture and other everyday products. The presence of BFRs has been documented in the environment, food, drinking water, inhaled dust and the human body. Due to the widespread exposure of the general population to BFRs and insufficient knowledge on their toxic action, including genotoxic potential, we have compared the effect of tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4,6,-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) on DNA damage in human peripheral blood mononuclear cells (PBMCs) (playing a crucial role in the immune system) as well as examined underlying mechanism of action of these substances. The cells were incubated for 24 h with studied compounds in the concentrations ranging from 0.01 to 10 µg/mL. The study has shown that examined BFRs induced single and, to a lesser extent, double strand-breaks formation and caused oxidative damage to pyrimidines, and particularly to purines in the incubated cells. PBMCs efficiently repaired the DNA strand-breaks induced by BFRs, but they were unable to remove completely damaged DNA (except cells treated with TBBPS). The greatest changes in the above-mentioned parameters were observed in cells incubated with TBBPA, while the smallest in PBMCs treated with TBBPS. The results have also revealed that tested compounds do not form adducts with DNA in PBMCs, while the observed changes were the most probably induced by indirect DNA-damaging agents, such as ROS and other reactive species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barańska, Woźniak, Mokra and Michałowicz.)

Brominated phenols (BPs) of anthropogenic origin are aromatic substances widely used in the industry as flame retardants (FRs) and pesticides as well as the components of FRs and polymers. In this review, we have focused on describing 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP), which are the most commonly used in the industry and are the most often detected in the air, aquatic and terrestrial ecosystems and the human body. This review describes human-related sources of these BPs that influence their occurrence in the environment (atmosphere, surface water, sediment, soil, biota), indoor air and dust, food, drinking water and the human organism. Data from in vitro and in vivo studies showing 2,4-DBP, 2,4,6-TBP and PBP toxicity, including their estrogenic activity, effects on development and reproduction, perturbations of cellular redox balance and cytotoxic action have been described. Moreover, the processes of BPs transformation that occur in human and other mammals, plants and bacteria have been discussed. Finally, the effect of abiotic factors (e.g. UV irradiation and temperature) on BPs conversion to highly toxic brominated dioxins and brominated furans as well as polybrominated biphenyls and polybrominated diphenyl ethers has been presented., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Cataract surgery is the most common surgery performed in the European Union (EU) annually. Analysis of Google Trends (GT) data could give European eye care providers useful information regarding interest in cataract surgery and potential barriers making patients unwilling to undergo surgery., Methods: Data were collected using GT for cataract surgery and the two most related queries, for each of 14 included countries from January 2004 to December 2018. Case volumes were extracted from the Eurostat report for the calendar years 2004-2018., Results: The most related queries analysis demonstrated surgery outcomes, founding issues and understanding of the disease as potential factors for patients considering cataract surgery. Trend analysis showed that the total search volumes for "cataract surgery" gradually increased over the study period. Also, for "cataract", "after cataract surgery", "cataract surgery NHF" rising trends were revealed. Trends found for "cataract surgery price" and "cataract surgery complications" were inconclusive. Univariate linear regression analysis demonstrated statistically significant correlations between average annual search volumes of "cataract surgery" and the annual volume of cataract surgeries performed in included countries, according to Eurostat data ( R 2  =  0.889, p = <.001). In addition, univariate linear regression analyses revealed similar, statistically significant correlation for each the most related queries., Conclusion: To the knowledge of the authors, this is the first and the only analysis of GT data in the ophthalmology literature to date. This study highlights this potentially powerful data set for European eye care providers.

Background: Left ventricular (LV) systolic impairment, particularly in the longitudinal direction, is considered an early and sensitive marker of hypertensive heart disease and increased cardiovascular risk. The evidence indicates that aortic stiffness and central hemodynamic factors are important determinants of LV performance, mediating the interaction between the heart and vascular load. Despite the existence of cross-sectional analyses linking central blood pressure (BP) parameters with LV mechanics, no longitudinal data are available which include serial measurements in the course of antihypertensive treatment., Objectives: To investigate the associations between changes in LV longitudinal and circumferential function with alterations in arterial hemodynamics and ventricular-arterial coupling (VAC) in patients with uncomplicated hypertension during a 12-month follow-up., Material and Methods: In this retrospective study, 216 patients (age 64.3 ±7.6 years) underwent echocardiography including left ventricular longitudinal (GLS) and circumferential strain (GCS) analysis, brachial BP measurements, VAC (combining echocardiography and brachial BP), and arterial hemodynamics using radial tonometry at baseline and after 12 months of antihypertensive therapy. Patients were grouped into 2 subsets: with improvement in GLS (n = 103) and with deterioration in GLS (n = 113)., Results: No significant differences were observed in the majority of cardiovascular, demographic or clinical characteristics between the groups. The subset with improvement in GLS demonstrated more favorable changes over follow-up in pulse wave velocity (p = 0.03), central augmentation pressure (p = 0.01) and ventricular-arterial coupling (p = 0.04) compared to patients showing deterioration in GLS. In the multivariable analysis, independent determinants of changes in GLS were: GLS at baseline (-0.48; p < 0.001), changes from baseline to follow-up in central augmentation pressure (-0.29; p = 0.002) and ventricular-arterial coupling (-0.25; p = 0.004). Independent determinants of analogous changes in GCS were: GCS at baseline (-0.46; p < 0.001) and changes in central augmentation pressure (-0.22; p = 0.02)., Conclusions: Left ventricular longitudinal and circumferential functional remodeling over time in hypertensive patients is associated with arterial hemodynamics and ventricular-arterial coupling.

Introduction: The process of scientific publishing changed greatly in the past decades. The authors aimed to get insight into the time required for articles to be accepted and released online in high-impacted ophthalmology journals., Methods: Comprehensive review of all original articles published by eight ophthalmology journals during a one-year period was performed for 2020 and 2005. Time taken from submission to acceptance and the first online release of the article was abstracted and analyzed., Results: A total of 3110 articles were reviewed. In 2020, the overall median time from submission to acceptance (AT) was 119 days (IQR 83-168) and 30 days (10-71) from acceptance to the first online release of the article (OP). AT increased by 7.3% from 2005 to 2020, whereas OP reduced by 73%. Publications, which the corresponding author was affiliated with US-located institution had shorter both AT and OP in 2005 and 2020. The author's specialty in ophthalmology had an inconclusive impact on AT and OP. Papers with multiple affiliated institutions had shorter AT and OP in both 2005 and 2020; however, these differences were not statistically significant., Conclusion: This study demonstrated that increasing pressure on authors, editors, and reviewers to publish articles and journals with high impact factor (IF) significantly influenced publication times in ophthalmology journals. Inflation of research papers was associated with rising AT time. A significant decrease in OP time was potentially explained by the editor's demand to achieve decent journal IF. This article brings to light relative publication times in the ophthalmology scientific journals., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Skrzypczak et al.)

Uncaria tomentosa (Willd.) DC is a woody climber species originating from South and Central America that has been used in the therapy of asthma, rheumatism, hypertension, and blood purification. Our previous study showed that U. tomentosa extracts altered human erythrocyte shape, which could be due to incorporation of the compounds contained in extracts into the erythrocyte membrane. The aim of the present study was to determine how the compounds contained in U. tomentosa extracts incorporate into the human erythrocyte membrane. The study has assessed the effect of aqueous and ethanolic extracts from leaves and bark of U. tomentosa on the osmotic resistance of the human erythrocyte, the viscosity of erythrocyte interior, and the fluidity of erythrocyte plasma membrane. Human erythrocytes were incubated with the studied extracts in the concentrations of 100, 250, and 500 µg/mL for 2, 5, and 24 h. All extracts tested caused a decrease in erythrocyte membrane fluidity and increased erythrocyte osmotic sensitivity. The ethanolic extracts from the bark and leaves increased viscosity of the erythrocytes. The largest changes in the studied parameters were observed in the cells incubated with bark ethanolic extract. We consider that the compounds from U. tomentosa extracts mainly build into the outer, hydrophilic monolayer of the erythrocyte membrane, thus protecting the erythrocytes against the adverse effects of oxidative stress.

We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM and from 0.5, to 250 μM, respectively. The expression profile of the following genes by quantitative Real-Time PCR was evaluated: Genes involved in the DNA methylation ( DNMT1 , DNMT3A ) and DNA demethylation process ( TET3 ) and those involved in chromatin remodeling: genes involved in the modification of histone methylation ( EHMT1 , EHMT2 ) and genes involved in the modification of histone deacetylation ( HDAC3 , HDAC5 ). Gene profiling showed that glyphosate changed the expression of DNMT1 , DMNT3A , and HDAC3 , while AMPA changed the expression of DNMT1 and HDAC3 . The results also revealed that glyphosate at lower concentrations than AMPA upregulated the expression of the tested genes. Both compounds studied altered expression of genes, which are characteristic for the regulation of transcriptionally inactive chromatin. However, the unknown activity of many other proteins involved in chromatin structure regulation prevents to carry out an unambiguous evaluation of the effect of tested xenobiotics on the studied process. Undoubtedly, we have observed that glyphosate and AMPA affect epigenetic processes that regulate chromatin architecture.

The human genome is persistently exposed to damage caused by xenobiotics, therefore the assessment of genotoxicity of substances having a direct contact with humans is of importance. Phthalates are commonly used in industrial applications. Widespread exposure to phthalates has been evidenced by their presence in human body fluids. We have assessed the genotoxic potential of selected phthalates and mechanism of their action in human peripheral blood mononuclear cells (PBMCs). Studied cells were incubated with di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP) and their metabolites: mono-n-butylphthalate (MBP), mono-benzylphthalate (MBzP) in the concentrations range of 0.1-10 µg/mL for 24 h. Analyzed compounds induced DNA single and double strand-breaks (DBP and BBP ≥ 0.5 µg/mL, MBP and MBzP ≥ 1 µg/mL) and more strongly oxidized purines than pyrimidines. None of the compounds examined was capable of creating adducts with DNA. All studied phthalates caused an increase of total ROS level, while hydroxyl radical was generated mostly by DBP and BBP. PBMCs exposed to DBP and BBP could not completely repair DNA strand-breaks during 120 min of postincubation, in opposite to damage caused by their metabolites, MBP and MBzP. We have concluded that parent phthalates: DBP and BBP caused more pronounced DNA damage compared to their metabolites.

Acute heart failure (AHF) syndromes are among the most frequent causes of hospitalization in the elderly and put a heavy financial burden on healthcare systems, mainly due to high early readmission rates. The understanding of AHF has evolved over the years from a significant hemodynamic failure to a multi-organ disease in the course of which peripheral mechanisms such as dysregulated cardiorenal axis or inflammation also play essential roles. A few available observational studies investigating iron deficiency (ID) in patients hospitalized for AHF indicate that this comorbidity is more prevalent than in chronic heart failure, and iron status presents some dynamics in these subjects. ID in AHF predicts increased mortality, greater risk for early readmission and is related to prolonged hospitalization. This paper reviews the results of the first multicenter, double-blind, randomized clinical trial on ferric carboxymaltose in patients who were stabilized after an episode of AHF who had concomitant ID (AFFIRM-AHF), and potential pathophysiological links between dysregulated iron status and AHF syndromes are discussed.

Brominated flame retardants (BFRs) are the compounds used in the industry in order to decrease flammability of various everyday products. The use of BFRs leads to migration of these substances into the environment, which results in the exposure of humans to their action. Although BFRs are widespread in human surrounding, the effect of these compounds on human body has been very poorly assessed. The purpose of this study was to evaluate cytotoxic effects as well as oxidative potential of selected bromophenolic flame retardants such as tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) on human peripheral blood mononuclear cells (PBMCs) that are crucial for proper functioning of the immune system. The cells were treated with the substances studied in the concentrations ranging from 0.0001 to 100 μg/mL for 1 h or 24 h. The results have shown that the compounds examined reduced PBMCs viability and ATP level as well as increased reactive oxygen species (including hydroxyl radical) formation. Moreover, the substances tested induced lipid peroxidation and caused oxidative damage to proteins in the incubated cells. It has also been noticed that the greatest changes were provoked by tetrabromobisphenol A, while the weakest by TBBPS, which is used as a substitute of TBBPA in the manufacture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Recently, many studies have been conducted trying to explain the molecular mechanism of curcumin action in various pathological states of the cell and the organism. Curcumin is considered to play a role in the regulation of T-lymphocytes function in the lymphoid tissue of the large intestine, apoptosis of the human papilloma and the activity of the 26S proteasome, and p53 level. Research works have shown that curcumin in tumor can regulate reactive oxygen species (ROS) and cytosolic calcium ion level as well as affect other signaling molecules [nuclear factor kappa B (NF-KB), cytokines] triggering endoplasmic reticulum and mitochondrial stress, and thus contributing to death of cancer cells. Curcumin can also arrest of the cell cycle in the G2/M phase leading to apoptosis and/or reduction in cancer cells proliferation. Moreover, curcumin is capable of crossing the blood-brain barrier, and thus it may protect the neurons from oxidative stress and inflammation. Finally, curcumin may play a role in cardiological protection and it is possible to use it in the protection of liver and spleen against oxidative and inflammatory injury. Among signaling pathways regulated by curcumin, the most important seem to be those related with regulation of oxidative stress and inhibition of NF-кB activity., (© 2020 John Wiley & Sons, Ltd.)

Glyphosate is used for cereal, vegetable and fruit crops for reducing or inhibiting the growth of weeds as well as a desiccant for various grain crops. That is why, glyphosate has been shown to be accumulated in humans and animals through ingestion of food of both plant and animal origin. The study aimed to assessed the effect of glyphosate, its metabolites: aminomethylphosphonic acid (AMPA), methylphosphonic acid and its impurities: PMIDA, N-methylglyphosate, hydroxymethylphosphonic acid and bis(phosphonomethyl)amine on apoptosis induction in human peripheral blood mononuclear cells (PBMCs). PBMCs were exposed to the compounds studied at the concentrations ranging from 0.01 to 5 mM for 4 h. We have observed an increase in reactive oxygen species (including hydroxyl radical) and cytosolic calcium ions levels as well as reduction of transmembrane mitochondrial potential (ΔΨm) in PBMCs exposed to the compounds examined. All substances studied changed PBMCs membrane permeability, activated caspase-8, -9, -3 and caused chromatin condensation, which showed that they were capable of inducing apoptosis both via extrinsic and particularly intrinsic pathway. Generally the study demonstrated that there were no differences between apoptotic changes induced by glyphosate, its metabolites or impurities, and observed changes were provoked by high concentrations of investigated compounds., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brominated flame retardants (BFRs) such as tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) as well as bromophenols, i.e. 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) have raised wide concerns due to their widespread occurrence in the environment and adverse effects observed in living organisms including human. The effect of BFRs on apoptosis of human erythrocytes has not been examined, that is why we have decided to assess eryptotic potential of these substances by determining changes in phosphatidylserine (PS) translocation, alterations in intracellular ROS and calcium ion levels, as well as caspase-3 and calpain activation in this cell type. It has been found that all BFRs studied even in the concentration of 0.001 μg/mL induced ROS formation. The compounds examined caused apoptosis by PS externalization and caspase-3 activation in human red blood cells. It has also been shown that calcium ions and calpain did not play a significant role in eryptosis induction by BFRs studied in human erythrocytes., (Copyright © 2018. Published by Elsevier Ltd.)

Glyphosate is the most heavily applied among pesticides in the world, and thus human exposure to this substance continues to increase. WHO changed classification of glyphosate to probably cancerogenic to humans, thus there is urgent need to assess in detail genotoxic mechanism of its action. We have assessed the effect of glyphosate, its formulation (Roundup 360 PLUS) and its main metabolite (aminomethylphosphonic acid, AMPA) in the concentration range from 1 to 1000 μM on DNA damage in human peripheral blood mononuclear cells (PBMCs). The cells were incubated for 24 h. The compounds studied and formulation induced DNA single and double strand-breaks and caused purines and pyrimidines oxidation. None of compounds examined was capable of creating adducts with DNA, while those substances increased ROS (including • OH) level in PBMCs. Roundup 360 PLUS caused damage to DNA even at 5 μM, while glyphosate and particularly AMPA induced DNA lesions from the concentration of 250 μM and 500 μM, respectively. DNA damage induced by glyphosate and its derivatives increased in order: AMPA, glyphosate, Roundup 360 PLUS. We may conclude that observed changes were not associated with direct interaction of xenobiotics studied with DNA, but the most probably they occurred through ROS-mediated effects., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Numerous research works have shown that synthesis of pesticides leads to the formation of impurities that may substantially enhance pesticide toxicity. In this study, the effect of manufacturing impurities of pesticide bromfenvinphos (BFVF) such as 1-bromo-2-(2,4-dichlorophenyl)-2-ethoxy ethene (BDCEE) and diethyl [2-(2,4-dichlorophenyl)-2-oxo-ethyl] phosphonate (β-ketophosphonate) on human erythrocytes, being significantly exposed to xenobiotics has been studied. The cells were treated with the compounds studied in the concentrations ranging from 0.1 μM to 250 μM for 4 h. In order to assess the effect of BDCEE and β-ketophosphonate on red blood cells hemolytic changes, changes in cell size (FSC parameter) and oxidation of hemoglobin were studied. Moreover, alterations in reactive oxygen species (ROS) formation, reduced glutathione (GSH) level and acetylcholinesterase (AChE) activity were determined. BDCEE induced an increase in ROS level and caused strong oxidation of hemoglobin as well as a slight change in erythrocytes size and hemolysis, while it did not change GSH level and AChE activity. β-ketophosphonate has not been shown to affect most parameters studied, but it strongly reduced AChE activity. Because changes in the parameters examined were noted at low concentrations of BFVF impurities (5-250 µM), those substances should not negatively affect on red blood cells of humans environmentally exposed to this pesticide.

Phenol and chlorinated phenols are widely spread in the environment and human surrounding, which leads to a common environmental and occupational exposure of humans to these substances. The aim of this study was to assess eryptotic changes in human red blood cells treated with phenol, 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP). The erythrocytes were incubated with phenols studied in the concentrations ranging from 1 to 100 μg/mL for 24 h or 48 h. The results of the study revealed that all compounds studied caused phosphatidylserine translocation and increased cytosolic calcium ions level in human erythrocytes. It was also noticed that phenol and chlorophenols caused an increase in caspase-3 and calpain activation, which confirmed that they were capable of inducing suicidal death of erythrocytes. The results also revealed that PCP most strongly altered the parameters studied, while phenol exhibited the weakest eryptotic potential in the incubated cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Because bisphenol A (BPA) and some of its analogs have been supposed to influence development of cancer, we have assessed the effect of BPA, bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) on DNA bases oxidation, which is a key process in cancer initiation. The analysis was conducted on human peripheral blood mononuclear cells (PBMCs), which are very useful model to assess genotoxic potential of various toxicants in different cell types. In order to determine oxidative damage to DNA pyrimidines and purines, alkaline version of the comet assay with DNA glycosylases, i.e. endonuclease III (Nth) and human 8-oxoguanine DNA glycosylase (hOGG1) was used. PBMCs were exposed to BPA or its analogs in the concentrations of 0.01, 0.1 and 1 μg/mL for 4 h and 0.001, 0.01 and 0.1 μg/mL for 48 h. We have observed that BPA, BPS, BPF and particularly BPAF caused oxidative damage to DNA pyrimidines and more strongly to purines in human PBMCs. The results have also shown that BPS, which is the most commonly used as a substitute for BPA in the manufacture induced definitely the smallest oxidative DNA bases lesions in PBMCs. Moreover, we have noticed that BPA, BPF and BPAF caused DNA damage at very low concentration of 1 ng/mL., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Bisphenols are massively used in the industry, and thus the exposure of biota including humans to these substances has been noted. In this study we have assessed the effect of BPA and its selected analogs, i.e. BPS, BPF and BPAF on membrane of human red blood cells, which is the first barrier that must be overcome by xenobiotics penetrating the cell, and is commonly utilized as a model in the investigation of the effect of different xenobiotics on various cell types. Red blood cells were incubated with BPA and its analogs in the concentrations ranging from 0.1 to 250 μg/ml for 4 h and 24 h. We have noted that the compounds studied altered membrane fluidity at its hydrophobic region, increased internal viscosity and osmotic fragility of the erythrocytes and altered conformational state of membrane proteins. Moreover, bisphenols examined increased thiol groups level, caused oxidative damage to membrane proteins, decreased ATP level, depleted the activity of Na+/K + ATPase and changed the activity of AChE in human red blood cells. It has been shown that the strongest changes were noted in cells treated with BPAF, while BPS caused the weakest (or none) alterations in the parameters studied., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Glyphosate is a very important herbicide that is widely used in the agriculture, and thus the exposure of humans to this substance and its metabolites has been noted. The purpose of this study was to assess DNA damage (determination of single and double strand-breaks by the comet assay) as well as to evaluate DNA methylation (global DNA methylation and methylation of p16 (CDKN2A) and p53 (TP53) promoter regions) in human peripheral blood mononuclear cells (PBMCs) exposed to glyphosate. PBMCs were incubated with the compound studied at concentrations ranging from 0.1 to 10 mM for 24 h. The study has shown that glyphosate induced DNA lesions, which were effectively repaired. However, PBMCs were unable to repair completely DNA damage induced by glyphosate. We also observed a decrease in global DNA methylation level at 0.25 mM of glyphosate. Glyphosate at 0.25 mM and 0.5 mM increased p53 promoter methylation, while it did not induce statistically significant changes in methylation of p16 promoter. To sum up, we have shown for the first time that glyphosate (at high concentrations from 0.5 to 10 mM) may induce DNA damage in leucocytes such as PBMCs and cause DNA methylation in human cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) and its analogs are widely used in the production of various everyday use products, which leads to a common exposure of humans to these substances. The effect of bisphenols on oxidative stress parameters has not been described in detail in non-nucleated cells, therefore, we have decided to evaluate the impact of BPA and its analogs, i.e. bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) on reactive oxygen species (ROS) formation, lipid peroxidation, glutathione (GSH) level and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in human erythrocytes. The erythrocytes were incubated with the compounds studied in the concentrations ranging from 0.1 to 500μg/ml for 1, 4 or 24h. It has been found that bisphenols enhanced ROS (including • OH) formation, depleted GSH level, increased lipid peroxidation and changed the activities of SOD, CAT and GSH-Px. It has been noted that the strongest alterations in ROS formation, lipid peroxidation and the activity of antioxidant enzymes were induced by BPAF, which changed CAT and SOD activity even at 0.5μg/ml. It has also been shown that BPA caused the strongest changes in GSH level, while BPS, which is the main BPA substituent in the manufacture did not alter most parameters studied., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the present study, we have investigated DNA-damaging potential of BPA and its analogs, i.e. bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) in human peripheral blood mononuclear cells (PBMCs) using the alkaline and neutral versions of the comet assay, which allowed to evaluate DNA single strand-breaks (SSBs) and double strand-breaks (DSBs). The use of the alkaline version of comet assay made also possible to analyze the kinetics of DNA repair in PBMCs after exposure of the cells to BPA or its analogs. We have observed an increase in DNA damage in PBMCs treated with BPA or its analogs in the concentrations ranging from 0.01 to 10 μg/ml after 1 and 4 h incubation. It was noted that bisphenols studied caused DNA damage mainly via SSBs, while DNA fragmentation via double DSBs was low. The strongest changes in DNA damage were provoked by BPA and particularly BPAF, which were capable of inducing SSBs even at 0.01 μg/ml, while BPS caused the lowest changes (only at 10 μg/ml). We have also observed that PBMCs significantly repaired bisphenols-induced DNA damage but they were unable (excluding cells treated with BPS) to repair totally DNA breaks., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide-glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01-10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances.

Bisphenols are important chemicals that are widely used in the manufacturing of polycarbonates, epoxy resin and thermal paper, and thus the exposure of humans to these substances has been noted. The purpose of this study was to assess eryptotic changes in human erythrocytes exposed (in vitro) to bisphenol A (BPA) and its selected analogs, i.e.,bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF). The erythrocytes were incubated with compounds studied at concentrations ranging from 1 to 250μg/mL for 4, 12 or 24h. The results showed that BPA and its analogs increased cytosolic calcium ions level with the strongest effect noted for BPAF. It has also been revealed that all bisphenols analyzed, and BPAF and BPF in particular increased phosphatidylserine translocation in red blood cells, which confirmed that they exhibited eryptotic potential in this cell type. Furthermore, it was shown that BPA and its analogs caused significant increase in calpain and caspase-3 activities, while the strongest effect was noted for BPAF. BPS, which is the main substituent of bisphenol A in polymers and thermal paper production exhibited similar eryptotic potential to BPA. Eryptotic changes in human erythrocytes were provoked by bisphenols at concentrations, which may influence the human body during occupational exposure or subacute poisoning with these compounds., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this study, the effect of monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), monobromoacetic acid (MBAA) and dibromoacetic acid (DBAA) on human peripheral blood mononuclear cells (PBMCs) was assessed. HAAs studied induced at millimolar concentrations necrotic alterations in PBMCs with the strongest effect noted for MBAA and DBAA. Chloro- and bromoacetic acids also provoked changes in PBMCs morphology because they caused a strong decrease in cell size (particularly DCAA and DBAA) and increase in cell granulation (mainly MBAA and DBAA). All HAAs studied, and DCAA and DBAA in particular (at lower concentrations than those, which caused necrosis) induced apoptotic changes, which was confirmed by analysis of alterations in cell membrane permeability and caspase 8, 9 and 3 activation. Moreover, HAAs examined (mainly dihalogenated acids) strongly increased transmembrane mitochondrial potential and enhanced ROS (mainly hydroxyl radical) formation, which was possibly associated with apoptotic changes provoked by those substances. The results showed that DBAA exhibited the strongest effects on PBMCs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Few studies have addressed the cellular effects of bisphenol S (BPS) and bisphenol AF (BPAF) on cells, and no study has been conducted to analyze the mechanism of action of bisphenols in blood cells. In this study, the effect of bisphenol A (BPA), bisphenol F (BPF), BPS and BPAF on human peripheral blood mononuclear cells (PBMCs) was analyzed. It was shown that BPA, BPF and BPAF in particular, decreased cell viability, which was associated with depletion of intracellular ATP level and alterations in PBMCs size and granulation. Bisphenols enhanced ROS (including OH˙) formation, which led to damage to lipids and proteins in PBMCs. The most significant alterations in ROS level were induced by BPF, and particularly BPAF. Moreover, it was shown that BPAF most strongly provoked lipid peroxidation, while BPA and BPS caused the greatest damage to proteins. It may be concluded that BPA and its analogs were capable of inducing oxidative stress and damage in PBMCs in the concentrations ranging from 0.06 to 0.5 μM (0.02-0.1 μg/ml), which may be present in human blood as a result of environmental exposure. Although, most of bisphenols studied decreased cell viability, size and ATP level at higher concentrations, BPAF exhibited its cytotoxic potential at low concentrations ranging from 0.3 to 3 μM (0.1-1.0 μg/ml) that may correspond to concentrations in humans following occupational exposure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)