The effects of bisphenols on the cardiovascular system ex vivo and in vivo.

The human population is regularly exposed to bisphenols. The first compound of this class, bisphenol A, is burdened by numerous reports of its potential toxicity and has been hence replaced by its analogues, so-called next generation bisphenols. Their widespread use has made them pervasive throughout the environment.

Interaction of Flavonoids with Zinc and Zinc-Containing Enzymes.

The current chelation therapy has several drawbacks, including lack of selectivity, which could lead to trace metal depletion. Consequently, the proper function of metalloenzymes can be disrupted. Flavonoids possess chelating properties and hence interfere with the homeostasis of essential metals.

The effects of bisphenols on the cardiovascular system.

Bisphenols, endocrine disrupting chemicals, have frequently been used for producing food packaging materials. The best-known member, bisphenol A (BPA), has been linked to impaired foetal development in animals. Possible negative effects of BPA on human health have resulted in the production of novel, so-called next-generation (NextGen) bisphenols whose effects on humans are much less explored or even missing.

Silymarin Dehydroflavonolignans Chelate Zinc and Partially Inhibit Alcohol Dehydrogenase.

Silymarin is known for its hepatoprotective effects. Although there is solid evidence for its protective effects against intoxication, only inconclusive data are available for alcoholic liver damage. Since silymarin flavonolignans have metal-chelating activity, we hypothesized that silymarin may influence alcoholic liver damage by inhibiting zinc-containing alcohol dehydrogenase (ADH).

Dehydroflavonolignans from Silymarin Potentiate Transition Metal Toxicity In Vitro but Are Protective for Isolated Erythrocytes Ex Vivo.

2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: in general, DHS appeared to be a more potent iron and copper chelator, and a copper reducing agent under acidic conditions, while DHSCH was a more potent copper reducing agent under neutral conditions.

Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin.

Silymarin is an extract from the seeds (fruits) of Silybum marianum that contains flavonolignans and flavonoids. Although it is frequently used as a hepatoprotective agent, its application remains somewhat debatable, in particular, due to the low oral bioavailability of flavonolignans. Moreover, there are claims of its potential interactions with concomitantly used drugs.

Applicability of the OECD 455 in-vitro assay for determination of hERa agonistic activity of isoflavonoids.

The Organisation for Economic Co-operation and Development (OECD)-validated transactivation assay using the human estrogen receptor alpha (hERα) Hela9903 cell line is used for activity evaluation of hERα agonists and antagonists. Due to many advantages, this assay is broadly used as an initial screening process. However, response significantly higher from that of 17-β estradiol (E2) was observed with phytoestrogens for concentrations commonly above 1 μM in previous studies.

4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects.

Scope: Intake of flavonoids from the diet can be substantial, and epidemiological studies suggest that these compounds can decrease the incidence of cardiovascular diseases by involvement with increased platelet aggregation. Although parent flavonoids possess antiplatelet effects, the clinical importance is disputable due to their very low bioavailability. Most of them are metabolized by human colon bacteria to smaller phenolic compounds, which reach higher plasma concentrations than the parent flavonoids.

The influence of microbial isoflavonoid specific metabolites on platelets and transition metals iron and copper.

Background: Isoflavonoids seem to possess positive cardiovascular and other beneficial effects in humans.

Hypothesis: Their low bioavailability, however, indicates that small isoflavonoid metabolites formed by human microflora can significantly contribute to these activities.

Study Design: Testing antiplatelet activity ex vivo in human blood and interaction with transition metals in vitro.

Hematoxylin assay of cupric chelation can give false positive results.

Some compounds without apparent chelation sites have been shown to chelate cupric ions using the hematoxylin assay. Since these compounds also have reduction potential (direct antioxidant effect), the aim of this study was to determine the possible interference of reducing agents with the hematoxylin assay. Four different known reducing agents (hydroxylamine, vitamin C, trolox - a water-soluble form of vitamin E and reduced glutathione /GSH/) were selected for the study together with oxidized glutathione (GSSG) for comparison.

Interaction of isolated silymarin flavonolignans with iron and copper.

Silymarin, the standardized extract from the milk thistle (Silybum marianum), is composed mostly of flavonolignans and is approved in the EU for the adjuvant therapy of alcoholic liver disease. It is also used for other purported effects in miscellaneous nutraceuticals. Due to polyhydroxylated structures and low systemic bioavailability, these flavonolignans are likely to interact with transition metals in the gastrointestinal tract.

A simple, cheap but reliable method for evaluation of zinc chelating properties.

Background: Zinc is an essential trace element. Both its lack and excess are associated with pathological states. The former is more common and can ensue from the excessive treatment with clinically used iron/copper chelators.

Mono and dihydroxy coumarin derivatives: Copper chelation and reduction ability.

Unlabelled: Due to the limited array of the currently available copper chelators, research of such compounds continues to be of clinical interest. Notably, o-dihydroxycoumarins have been previously shown to be potent iron chelators under neutral conditions. Within this study, the interaction of a series of natural coumarins and their synthetic analogs with copper has been evaluated in order to obtain structure-activity relationships under different pathophysiological pH conditions.

The Stoichiometry of Isoquercitrin Complex with Iron or Copper Is Highly Dependent on Experimental Conditions.

Interaction of flavonoids with transition metals can be partially responsible for their impact on humans. Stoichiometry of the iron/copper complex with a flavonoid glycoside isoquercitrin, a frequent component of food supplements, was assessed using competitive and non-competitive methods in four (patho)physiologically-relevant pH values (4.5.