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1.
Bisphenol A and Male Fertility: Myths and Realities.
Castellini, C, Totaro, M, Parisi, A, D'Andrea, S, Lucente, L, Cordeschi, G, Francavilla, S, Francavilla, F, Barbonetti, A
Frontiers in endocrinology. 2020;:353
Abstract
Bisphenol A (BPA) represents the main chemical monomer of epoxy resins and polycarbonate plastics. The environmental presence of BPA is widespread, and it can easily be absorbed by the human body through dietary and transdermal routes, so that more than 90% of the population in western countries display detectable BPA levels in the urine. As BPA is qualified as an endocrine disruptor, growing concern is rising for possible harmful effects on human health. This review critically discusses the available literature dealing with the possible impact of BPA on male fertility. In rodent models, the in vivo exposure to BPA negatively interfered with the regulation of spermatogenesis throughout the hypothalamic-pituitary-gonadal axis. Furthermore, in in vitro studies, BPA promoted mitochondrial dysfunction and oxidative/apoptotic damages in spermatozoa from different species, including humans. To date, the claimed clinical adverse effects on male fertility are largely based on the results from studies assessing the relationship between urinary BPA concentration and conventional semen parameters. These studies, however, produced controversial evidence due to heterogeneity in the extent of BPA exposure, type of population, and enrollment setting. Moreover, the cause-effect relationship cannot be established due to the cross-sectional design of the studies as well as the large spontaneous between- and within-subject variability of semen parameters. The best evidence of an adverse effect of BPA on male fertility would be provided by prospective studies on clinically relevant endpoints, including natural or medically assisted pregnancies among men either with different exposure degrees (occupational/environmental) or with different clinical conditions (fertile/subfertile).
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2.
Pharmacokinetic Parameters of Watermelon (Rind, Flesh, and Seeds) Bioactive Components in Human Plasma: A Pilot Study to Investigate the Relationship to Endothelial Function.
Fan, J, Park, E, Zhang, L, Edirisinghe, I, Burton-Freeman, B, Sandhu, AK
Journal of agricultural and food chemistry. 2020;(28):7393-7403
Abstract
This study aimed to investigate the metabolic fate of bioactive components in watermelon and explore their effect on endothelial function. Six healthy overweight/obese (BMI: 28.7 ± 1.6 kg/m2) adults received 100 kcal of watermelon flesh (WF), rind (WR), seeds (WS), or control meal. l-Citrulline, arginine, and (poly)phenolic metabolites were characterized in plasma over 24 h using UHPLC-MS. Endothelial function was assessed using a flow mediated dilation (FMD) technique over 7 h. Maximum concentration (Cmax) and area under the curve (AUC0-8h) of l-citrulline were significantly higher after WF- and WR-containing test meals compared to control (p < 0.05). Likewise, several individual phenolic metabolites in plasma had significantly higher Cmax after WR, WF, or WS intake compared to control. FMD responses were not different among test meals. Our results provide insights on circulating metabolites from watermelon flesh, seed, and rind and lay the foundation for future clinical trials on vascular benefits of watermelon.
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3.
Inhibition of UDP-glucuronosyltransferases (UGTs) by bromophenols (BPs).
Wang, F, Wang, S, Yang, K, Liu, YZ, Yang, K, Chen, Y, Fang, ZZ
Chemosphere. 2020;:124645
Abstract
Bromophenols (BPs) are important organic compounds which have become dominant pollutants during these years. Our present study investigated the potential inhibition behaviour of BPs on the activity of one of the most important phase II drug-metabolizing enzymes (DMEs), UDP-glucuronosyltransferases (UGTs). Recombinant UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was utilized as the probe reaction. 100 μM of BPs was utilized as the inhibition screening concentrations, and the complete inhibition profile of UGT isoforms by BPs was obtained. UGT1A7 was the most vulnerable UGT isoform towards BPs. Some structure-activity relationship for the inhibition of UGTs by BPs was found, and this relationship can be furtherly explained by the hydrophobic contacts of BPs with the activity cavity of UGTs using in silico docking method. The inhibition kinetics determination showed that the inhibition kinetic parameter Ki value was calculated to be 2.85, 3.99 and 31.00 μM for the inhibition of UGT1A3, UGT1A7, and UGT2B7 by representative BPs, 2,4,6-TBP. Combined with in vivo exposure concentration of 2,4,6-TBP, in vitro-in vivo extrapolation (IVIVE) was employed to demonstrate the moderate possibility for the inhibition of UGT1A3 and UGT1A7 by 2,4,6-TBP. In conclusion, our study gave the full description towards the inhibition of BPs towards UGT isoforms, which will provide a new perspective for elucidating the toxicity mechanism of bromophenols (BPs).
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4.
The impact of xenoestrogens on effectiveness of treatment for hormone-dependent breast cancer - current state of knowledge and perspectives for research.
Boszkiewicz, K, Sawicka, E, Piwowar, A
Annals of agricultural and environmental medicine : AAEM. 2020;(4):526-534
Abstract
INTRODUCTION Breast cancer is the most common cancer occurring in women and causing the highest number of deaths among them. The role of xenoestrogens has been the subject of many studies in the pathogenesis of breast cancer. Less is known about the impact of xenoestrogens on the effectiveness of hormone therapy used to treat breast cancer, and thus possible drug-xenostrogen interactions. OBJECTIVE The aim of this review is to summarize the current state of knowledge and present perspectives for further research on the impact of xenoestrogens on the effectiveness of drugs used in the treatment of hormone-dependent breast cancer. CURRENT STATE OF KNOWLEDGE Phytoestrogens, in particular flavonoid genistein, are the best studied group of xenoestrogens in terms of interaction with drugs used in the treatment of breast cancer, due to their frequent use, including their use in alleviating the adverse effects of hormone therapy. Analyzing the current state of knowledge, it seems that phytoestrogens intake should be avoided during conventional anti-cancer treatment. Of the other xenoestrogens, bisphenol A (BPA) is one of the best-tested compounds for interactions with drugs used to treat breast cancer. It has been shown that bisphenol A could reduced therapeutic effect of active tamoxifen metabolite and cytostatics used in breast cancer treatment. CONCLUSIONS Confirmation in clinical trials of the results obtained in vitro and in vivo tests, would enable the creation of specific recommendations for patients undergoing breast cancer treatment, especially hormone therapy. An area requiring further research is the analysis of the effects of xenoestrogens other than phytoestrogens, e.g. metalloestrogens, on the effects of drugs used in the treatment of breast cancer.
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5.
A combined experimental and computational study on the oxidative degradation of bromophenols by Fe(VI) and the formation of self-coupling products.
Dar, AA, Chen, J, Shad, A, Pan, X, Yao, J, Bin-Jumah, M, Allam, AA, Huo, Z, Zhu, F, Wang, Z
Environmental pollution (Barking, Essex : 1987). 2020;:113678
Abstract
In this study, the degradation of eight bromophenols (BPs), including monobromophenols (2-BP, 3-BP, and 4-BP), dibromophenols (2,4-DBP, 2,6-DBP, and 3,5-DBP), a tribromophenol (2,4,6-TBP) and a pentabromophenol (PBP), by a Fe(VI) reaction process at a pH of 8.0 was systematically studied. It was concluded that their degradation rates increased with increasing Fe(VI) concentrations in solution. The removal of 2,4,6-TBP, 2-BP, and 2,6-DBP was faster than that of the other five BPs, which could be attributed to the position of the substituting Br atom. Moreover, the direct oxidation and coupling reactions greatly influenced the reactivity of the bromophenols with Fe(VI). The electron paramagnetic resonance (EPR) analysis confirmed the presence of hydroxyl radicals in present system. The oxidation reaction products of PBP and 2-BP were recognized by an electrospray time-of-flight mass spectrometer; hydroxylation, hydroxyl substitution, the cleavage of the C-C bond, direct oxidation and polymerization via an end linking mechanism were noticeably found in the reaction process, resulting in the formation of polymerization products and causing hydroxylation to occur. Theoretical calculations further determined the possible oxidation sites of 2-BP and PBP. This study may provide comprehensive and important information on the remediation of BPs by Fe(VI).
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6.
Bisphenol A impaired cell adhesion by altering the expression of adhesion and cytoskeleton proteins on human podocytes.
Moreno-Gómez-Toledano, R, Arenas, MI, González-Martínez, C, Olea-Herrero, N, Reventún, P, Di Nunzio, M, Sánchez-Esteban, S, Arilla-Ferreiro, E, Saura, M, Bosch, RJ
Scientific reports. 2020;(1):16638
Abstract
Bisphenol A (BPA), a chemical -xenoestrogen- used in food containers is present in the urine of almost the entire population. Recently, several extensive population studies have proven a significant association between urinary excretion of BPA and albuminuria. The alteration of glomerular podocytes or "podocytopathy" is a common event in chronic albuminuric conditions. Since many podocytes recovered from patients' urine are viable, we hypothesized that BPA could impair podocyte adhesion capabilities. Using an in vitro adhesion assay, we observed that BPA impaired podocyte adhesion, an effect that was abrogated by Tamoxifen (an estrogen receptor blocker). Genomic and proteomic analyses revealed that BPA affected the expression of several podocyte cytoskeleton and adhesion proteins. Western blot and immunocytochemistry confirmed the alteration in the protein expression of tubulin, vimentin, podocin, cofilin-1, vinculin, E-cadherin, nephrin, VCAM-1, tenascin-C, and β-catenin. Moreover, we also found that BPA, while decreased podocyte nitric oxide production, it lead to overproduction of ion superoxide. In conclusion, our data show that BPA induced a novel type of podocytopathy characterizes by an impairment of podocyte adhesion, by altering the expression of adhesion and cytoskeleton proteins. Moreover, BPA diminished production of podocyte nitric oxide and induced the overproduction of oxygen-free metabolites. These data provide a mechanism by which BPA could participate in the pathogenesis and progression of renal diseases.
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7.
Honey and Its Phenolic Compounds as an Effective Natural Medicine for Cardiovascular Diseases in Humans?
Olas, B
Nutrients. 2020;(2)
Abstract
Honey is a sweet, viscous syrup produced by the honey bee (Apis mellifera). It is probably the first natural sweetener ever discovered, and is currently used as a nutritious food supplement and medicinal agent. The aim of the present mini-review is to summarize and update the current knowledge regarding the role of honey in CVDs based on various experimental models. It also describes the role of its phenolic compounds in treating CVDs. Many such phenolic and flavonoid compounds, including quercetin, kaempferol, apigenin, and caffeic acid, have antioxidant and anti-platelet potential, and hence may ameliorate cardiovascular diseases (CVDs) through various mechanisms, such as by decreasing oxidative stress and inhibiting blood platelet activation. However, as the phenolic content of a particular type of honey is not always known, it can be difficult to determine whether any observed effects on the human cardiovascular system may be associated with the consumption of honey or its constituents. Therefore, further experiments in this area are needed.
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8.
Inhibitory effect of phenolic compounds and plant extracts on the formation of advance glycation end products: A comprehensive review.
Khan, M, Liu, H, Wang, J, Sun, B
Food research international (Ottawa, Ont.). 2020;:108933
Abstract
Advance glycation end products (AGEs) are a diverse group of compounds formed through the non-enzymatic maillard reaction of reducing sugars with the free amino groups in proteins, lipids or nucleic acids. Accumulation of AGEs has been suggested to be a pathogenic mechanism of oxidative stress, inflammation and structural tissue damage leading to chronic vascular problems in many ailments including diabetes, atherosclerosis, neuropathy, retinopathy, nephropathy, aging, and chronic renal disease. Treatment with AGEs inhibitors is believed to be a potential strategy for preventing lifestyle-related diseases. To inhibit the AGEs development is supposed to show part in the inhibition of diabetic problems. Study of dietary bioactive combinations with antiglycation properties delivers future views for inhibition or mediation associated to AGEs complications. Many study show the possibility of dietary constituents to stop AGE development. Therefore, search for natural compounds able to prevent glycation and have the potential therapeutic ability to inhibit diabetes and age associated diseases. The purpose of this review is to critically evaluate the existing literature on different phenolics on AGEs inhibition.
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9.
Bisphenols and Male Reproductive Health: From Toxicological Models to Therapeutic Hypotheses.
De Toni, L, De Rocco Ponce, M, Petre, GC, Rtibi, K, Di Nisio, A, Foresta, C
Frontiers in endocrinology. 2020;:301
Abstract
Bisphenols, and in particular bisphenol A (BPA), have been widely used for the production of plastic manufacts in the last 50 years. Currently, BPA is present in a variety of daily use polycarbonate plastics and epoxy resins, and dietary ingestion is considered the main route of human exposure. Accordingly, BPA is the chemical pollutant with the widest exposure in humans, involving nearly 90% of general population, according to recent studies. Concerns about BPA effects on human health date back to 1930s, when severe impact on male sexual development was suggested. Now, the acknowledged biological effects of BPA are various. In regard to human fertility, BPA has been shown to disrupt hormone signaling even at low concentrations. Results from human epidemiological studies have reported BPA interference with follicle stimulating hormone, inhibin B, estradiol, testosterone levels, and sexual function in male subjects. Moreover, recent studies have reported an association between BPA levels and reduced sperm concentration, motility, normal morphology, sperm DNA damage, and altered epigenetic pattern, resulting in trans-generational legacy of BPA effects. In this review, the recognized effects of BPA on male reproductive health are described, from the most recent issues on experimental models to epidemiological data. In addition, the very recent interest about the use of nutraceutical remedies to counteract BPA effects are discussed.
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10.
Beer Phenolic Composition of Simple Phenols, Prenylated Flavonoids and Alkylresorcinols.
Boronat, A, Soldevila-Domenech, N, Rodríguez-Morató, J, Martínez-Huélamo, M, Lamuela-Raventós, RM, de la Torre, R
Molecules (Basel, Switzerland). 2020;(11)
Abstract
Beer is a fermented beverage with beneficial phenolic compounds and is widely consumed worldwide. The current study aimed to describe the content of three families of phenolic compounds with relevant biological activities: prenylated flavonoids (from hops), simple phenolic alcohols (from fermentation) and alkylresorcinols (from cereals) in a large sample of beers (n = 45). The prenylated flavonoids analyzed were xanthohumol, isoxanthohumol, 6- and 8-prenylnaringenin. The total prenylated flavonoids present in beer ranged from 0.0 to 9.5 mg/L. The simple phenolic alcohols analyzed were tyrosol and hydroxytyrosol, ranging from 0.2 to 44.4 and 0.0 to 0.1 mg/L, respectively. Our study describes, for the first time, the presence of low amounts of alkylresorcinols in beer, in concentrations ranging from 0.02 to 11.0 µg/L. The results in non-alcoholic beer and the differences observed in the phenolic composition among different beer types and styles highlight the importance of the starting materials and the brewing process (especially fermentation) on the final phenolic composition of beer. In conclusion, beer represents a source of phenolic compounds in the diet that could act synergistically, triggering beneficial health effects in the context of its moderate consumption.