Computational Chemistry Strategies to Investigate the Antioxidant Activity of Flavonoids-An Overview.

Despite several decades of research, the beneficial effect of flavonoids on health is still enigmatic. Here, we focus on the antioxidant effect of flavonoids, which is elementary to their biological activity. A relatively new strategy for obtaining a more accurate understanding of this effect is to leverage computational chemistry.

The chemical reactivity of (-)-epicatechin quinone mainly resides in its B-ring.

As one of the important dietary antioxidants, (-)-epicatechin is a potent reactive oxygen species (ROS) scavenger involved in the redox modulation of the cell. When scavenging ROS, (-)-epicatechin will donate two electrons and become (-)-epicatechin quinone, and thus take over part of the oxidative potential of the ROS. The aim of the study is to determine where this chemical reactivity resides in (-)-epicatechin quinone.

Activation versus inhibition of microsomal glutathione S-transferase activity by acrolein. Dependence on the concentration and time of acrolein exposure.

The toxicity of acrolein, an α,β-unsaturated aldehyde, is due to its soft electrophilic nature and primarily involves the adduction of protein thiols. The thiol glutathione (GSH) forms the first line of defense against acrolein. The present study confirms that acrolein added to isolated rat liver microsomes can increase microsomal GSH transferase (MGST) activity 2-3 fold, which can be seen as a direct adaptive increase in the protection against acrolein.

Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones.

Here we describe the synthesis and the antifibrotic and anticancer activity determination of amino(imino)thiazolidinone derivatives. An efficient one-pot three-component reaction which involved [2 + 3]-cyclocondensation and Knoevenagel condensation was used for the synthesis of 5-ene-2-amino(imino)-4-thiazolidinones. Following amino-imino tautomerism, the compound structures were confirmed by X-ray analysis.

The oxidation of p-phenylenediamine, an ingredient used for permanent hair dyeing purposes, leads to the formation of hydroxyl radicals: Oxidative stress and DNA damage in human immortalized keratinocytes.

The hair-dyeing ingredient, p-phenylenediamine (PPD), was previously reported to be mutagenic, possibly by inducing oxidative stress. However, the exact mechanism of PPD in inducing oxidative stress upon skin exposure during hair-dyeing in human keratinocytes remains unknown. The aim of our studies was therefore to investigate the toxicity of PPD and its by-products in human immortalized keratinocytes (HaCaT) after auto-oxidation and after reaction with hydrogen peroxide (H2O2).

Protective Pleiotropic Effect of Flavonoids on NAD⁺ Levels in Endothelial Cells Exposed to High Glucose.

NAD(+) is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD(+) levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quercetin, and flavone) during high glucose conditions in an in vitro model using human umbilical vein endothelial cells (HUVECs).

Exhaled biomarkers and gene expression at preschool age improve asthma prediction at 6 years of age.

Rationale: A reliable asthma diagnosis is difficult in wheezing preschool children.

Objectives: To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children.

Methods: Two hundred two preschool recurrent wheezers (aged 2-4 yr) were prospectively followed up until 6 years of age.

Effect of Nɛ-carboxymethyllysine on oxidative stress and the glutathione system in beta cells.

One of the pathways involved in the pathogenesis of diabetic complications is the formation of excessive levels of advanced glycation end (AGE) products. N-carboxymethyllysine (CML) is one of the best-characterized AGEs. Because little is known about the effects of AGEs on pancreatic beta cells, we investigated the effect of CML on human pancreatic cells and determined the activity and gene expression of glutathione system components.

Integrative genomic analysis identifies a role for intercellular adhesion molecule 1 in childhood asthma.

Background: Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development.

Superoxide anion radicals activate hepatic stellate cells after entry through chloride channels: a new target in liver fibrosis.

It is generally accepted that reactive oxygen species (ROS) play an important role in the pathogenesis of liver fibrosis. ROS, however, constitute a group of species with varying properties making it likely that their contribution to the pathological mechanism varies. LX-2 hepatic stellate cells (HSCs) were exposed to superoxide anion radicals (O2(·-)) generated by xanthine and xanthine oxidase.

Accelerated aging during chronic oxidative stress: a role for PARP-1.

Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence.

Elevated citrate levels in non-alcoholic fatty liver disease: the potential of citrate to promote radical production.

Plasma citrate levels were found to be elevated in non-alcoholic fatty liver disease (NAFLD) patients. Cellular experiments indicated that increased citrate levels might originate from an excess of fatty acids. The impact of elevated citrate levels on oxidative stress was examined.

Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.

Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats.

Identification of the metabolites of the antioxidant flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside in mice.

The clinical use of the anticancer drug doxorubicin is limited by severe cardiotoxicity. In mice, the semisynthetic antioxidant flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside (monoHER) has been successfully used as a protector against doxorubicin-induced cardiotoxicity. However, most monoHER has already been cleared from the body at the time that doxorubicin concentrations are still high.

Oxidative stress and antioxidants in interstitial lung disease.

Purpose Of Review: The cause of interstitial lung diseases (ILDs) such as lung fibrosis or sarcoidosis is still largely unknown. Pharmacotherapeutic treatment in ILD lacks a firm mechanistic molecular basis. A striking paradox is that ILDs result in a shortage of oxygen and that at the same time reactive oxygen species are responsible for the tissue damage in ILDs.

Erythritol is a sweet antioxidant.

Objective: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.

Superoxide radicals increase transforming growth factor-beta1 and collagen release from human lung fibroblasts via cellular influx through chloride channels.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of fibrosis. However, it remains unclear which ROS is the major cause. We hypothesize that superoxide elicits specific toxicity to human lung fibroblasts and plays an important role in the development of pulmonary fibrosis.

Partial bladder outlet obstruction reduces the tissue antioxidant capacity and muscle nerve density of the guinea pig bladder.

Aims: Reactive nitrogen and oxygen species (RNOS) likely play a role in the development of bladder dysfunction related to bladder outlet obstruction. Antioxidants protect against these free radicals. The aim of our study was to investigate the effect of bladder outlet obstruction on the endogenous antioxidant status of the bladder and to correlate this to bladder structure and function.

Damage to lung epithelial cells and lining fluid antioxidant defense by humic acid.

Humic acid causes diseases including lung emphysema and fibrosis. Emerging evidence indicates that oxidative stress is involved in humic acid-induced effects. In the present study, we investigated generation of hydroxyl radicals from humic acid, as well as the effects of humic acid to lung epithelial cells and artificial alveolar lining fluid antioxidant mixture.

New iron chelators in anthracycline-induced cardiotoxicity.

The use of anthracycline anticancer drugs is limited by a cumulative, dose-dependent cardiac toxicity. Iron chelation has long been considered as a promising strategy to limit this unfavorable side effect, either by restoring the disturbed cellular iron homeostasis or by removing redox-active iron, which may promote anthracycline-induced oxidative stress. Aroylhydrazone lipophilic iron chelators have shown promising results in the rabbit model of daunorubicin-induced cardiomyopathy as well as in cellular models.

Free radicals in exhaled breath condensate in cystic fibrosis and healthy subjects.

Many markers of airway inflammation and oxidative stress can be measured non-invasively in exhaled breath condensate (EBC). However, no attempt has been made to directly detect free radicals using electron paramagnetic resonance (EPR) spectroscopy. Condensate was collected in 14 children with cystic fibrosis (CF) and seven healthy subjects.

Lecithinized copper,zinc-superoxide dismutase as a protector against doxorubicin-induced cardiotoxicity in mice.

Production of superoxide radicals from doxorubicin is widely accepted to be the cause of the cardiotoxicity induced by this antitumor agent. Pretreatment with superoxide dismutase could improve the therapeutic application. Aim of the present study was to determine whether lecithinized superoxide dismutase (PC-SOD) can serve as a cardioprotective drug during doxorubicin treatment.

Superoxide dismutase: the balance between prevention and induction of oxidative damage.

Cu,Zn-superoxide dismutase (SOD1) has been shown to be effective in several free radical mediated diseases, although some studies have pointed toward SOD1 toxicity at a high concentrations. In the present study, the balance between prevention and induction of damage by SOD1 has been investigated both in vitro and in vivo. In vitro superoxide was generated using xanthine/xanthine oxidase.

Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants.

Catechol-containing antioxidants are able to protect against lipid peroxidation by nonenzymatic scavenging of free radicals with their catechol moiety. During their antioxidant activity, catechol oxidation products such as semiquinone radicals and quinones are formed. These oxidation products of 4-methylcatechol inactivate the GSH-dependent protection against lipid peroxidation and the calcium sequestration in liver microsomes.

Hypochlorous acid is a potent inhibitor of acetylcholinesterase.

The role of hydrogen peroxide and peroxynitrite in the induction of airway hyperreactivity has been well described. Another reactive species which is formed during airway inflammation is hypochlorous acid (HOCl). In the present investigation the effect of HOCl on cholinergic innervation of the airway was investigated.