Natural Antioxidants Quercetin Research Articles

Nanoformulations of quercetin for controlled delivery: a review of preclinical anticancer studies.

One of the well-studied older molecules, quercetin, is found in large quantities in many fruits and vegetables. Natural anti-oxidant quercetin has demonstrated numerous pharmacological properties in preclinical and clinical research, including anti-inflammatory and anti-cancer effects. Due to its ability to control cell signaling pathways, including NF-κB, p53, activated protein-1 (AP-1), STAT3, and epidermal growth response-1 (Egr-1), which is essential in the initiation and proliferation of cancer, it has gained a lot of fame as an anticancer molecule. Recent research suggests that using nanoformulations can help quercetin to overcome its hydrophobicity while also enhancing its stability and cellular bioavailability both in vitro and in vivo. The main aim of this review is to focus on the comprehensive insights of several nanoformulations, including liposomes, nano gels, micelles, solid lipid nanoparticles (SLN), polymer nanoparticles, gold nanoparticles, and cyclodextrin complexes, to transport quercetin for application in cancer.

Doxorubicin and Quercetin Double Loading in Modified MCM-41 Lowered Cardiotoxicity in H9c2 Cardioblast Cells In Vitro.

One of the therapeutic limitations of the use of doxorubicin (DOX) as an anticancer drug is its cardiotoxicity. Its hydrophilicity also causes difficulties in achieving sustained release. The simultaneous delivery with the well-known natural antioxidant quercetin could ameliorate its cardiotoxicity. Thus, the main aim of this work is to study the potential of carboxylated and non-carboxylated mesoporous silica MCM-41 nanoparticles for double loading of the hydrophilic doxorubicin hydrochloride and hydrophobic quercetin (Q) in one nanocarrier with a modified release pattern to reduce the cardiotoxic side effects of doxorubicin in vitro. The methods included the modification of MCM-41, single and double loading of modified and non-modified MCM-41, physicochemical characterization, in vitro release tests and kinetic study, and in vitro cell viability studies. Doxorubicin and quercetin were successfully double-loaded with encapsulation efficiency (EE) of 43 ± 4.1% and 37 ± 4.5%, respectively, in native MCM-41. The post-synthetic carboxylation led to 49 ± 4.3% EE (DOX) and 36 ± 4.0% (Q) and double lowering of the cardiotoxicity on H9c2 (IC50 = 5.96 µm). Sustained release profiles over 72 h were achieved. A successful procedure was proposed for the efficient double loading of a hydrophilic drug and a hydrophobic drug. The carboxy-modified double-loaded nanosystems demonstrate a decreased in vitro cardiotoxicity of doxorubicin and can be considered as a potential chemotherapeutic formulation.

Antioxidant Activity of Quercetin in a H2O2-Induced Oxidative Stress Model in Red Blood Cells: Functional Role of Band 3 Protein.

During their lifespan, red blood cells (RBCs) are exposed to a large number of stressors and are therefore considered as a suitable model to investigate cell response to oxidative stress (OS). This study was conducted to evaluate the potential beneficial effects of the natural antioxidant quercetin (Q) on an OS model represented by human RBCs treated with H2O2. Markers of OS, including % hemolysis, reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS) levels, oxidation of protein sulfhydryl groups, CD47 and B3p expression, methemoglobin formation (% MetHb), as well as the anion exchange capability through Band 3 protein (B3p) have been analyzed in RBCs treated for 1 h with 20 mM H2O2 with or without pre-treatment for 1 h with 10 μM Q, or in RBCs pre-treated with 20 mM H2O2 and then exposed to 10 µM Q. The results show that pre-treatment with Q is more effective than post-treatment to counteract OS in RBCs. In particular, pre-exposure to Q avoided morphological alterations (formation of acanthocytes), prevented H2O2-induced OS damage, and restored the abnormal distribution of B3p and CD47 expression. Moreover, H2O2 exposure was associated with a decreased rate constant of SO42− uptake via B3p, as well as an increased MetHb formation. Both alterations have been attenuated by pre-treatment with 10 μM Q. These results contribute (1) to elucidate OS-related events in human RBCs, (2) propose Q as natural antioxidant to counteract OS-related alterations, and (3) identify B3p as a possible target for the treatment and prevention of OS-related disease conditions or aging-related complications impacting on RBCs physiology.

Comparative efficacy of transdermal forms for alopecia therapy

Introduction. Alopecia is a polyetiological disorder characterized by hair loss and reducing their number per unit area. Baldness causes psychological and social discomfort to patients, in connection with what an important task is to develop formulations that are more effective than the reference agents.Aim. Investigate the possibility of applying the original substance Y in several dosage forms for the treatment of alopecia in comparison with reference drugs: minoxidil and burdock oil.Materials and methods. The research subject was the original substance Y, for which several dosage forms were made: gel, alcohol and oil compositions. The study on the effectiveness and safety of the developed formulations was carried out on 9 groups of male C57BL/6 mice. Depilation with further assessment of the percentage of hair follicles in the growth and resting phases was tested as a pre-clinical model of alopecia. In the study of the mechanism of action of substance Y, chemiluminescent assay was performed compared with natural antioxidant quercetin in the system luminol – 2,2'-azo-bis(2-amidinopropane)dihydrochloride, in potassium-phosphate buffer medium (pH = 7.4). Statistical processing of the results was carried out using two-way ANOVA using GraphPad Prism 8.0.2, USA software at the level of statistical significance of differences p < 0.05 and p < 0.005.Results and discussion. Based on the results of histological analysis and visual changes, it was found that the effectiveness of the topical forms of substance Y decreases in the following order: gel, alcohol form, oil composition. The use of a combination of the gel base with the test substance Y resulted to the appearance of a larger number of hair follicles in the growth phase than when using the reference preparation – 2 % minoxidil solution (the differences are statistically significant). Chemiluminescent assessment of antioxidant activity showed the lack of antioxidant effect in substance Y.Conclusion. The study combines two pharmaceutical profiles: technological and pharmacological. In the course of the experiments, the prospects of the gel form of the original substance Y for topical therapy of alopecia were shown. In the near future, it is planned to study the mechanism of action of substance Y, as well as registration of patent protection for a new drug.

Fluorescence determination of quercetin in food samples using polyhedron-shaped MOF@MOF(NUZ-8) based on NH2-UiO-66 and ZIF-8.

A new metal-organic framework compound (MOF@MOF, NUZ-8) comprised of NH2-UiO-66 and ZIF-8 under the polyvinylpyrrolidone (PVP) as the structure modifier was synthesized through an internal extended growth method (IEGM). The resulting NUZ-8 emerged the unreported unique polyhedron shape and showed considerable specific surface area (1466.1862m2/g), excellent adsorption capacity, and fluorescence. NUZ-8 was used as a probe for the rapid optical detection of natural antioxidant quercetin (QCT). Its outstanding selectivity and sensitivity to QCT are derived from the fact that NH2-UiO-66 acted as an optical tentacle to perceive QCT in virtue of its luminescence advantages, and ZIF-8 realized the selective enrichment of the QCT through its electron-rich framework structure. The experiments were carried out at an excitation wavelength of 335nm and an emission wavelength range of 370-530nm. Under conditions of the investigation, this probe realized the rapid detection of QCT and considerable adsorption capacity with wide linearity (0.3-80μM), a low detection limit (0.14μM), and acceptable recoveries (84.0-97.0%) in red wine samples, propertieswhich were superior to many other detection platforms. The synthesis and the use of the above polyhedral composite provide guidance for the application of the IEGM in enhancing chemical sensing and instant determination of drugs.Graphical abstract Flow chart of this paper.

Biomaterials Containing the Natural Antioxidant Quercetin: Synthesis and Health Benefits

AbstractQuercetin, whose health‐promoting effects are acclaimed, is entrapped in a silica‐based and silica/polymer hybrid material via sol–gel route, to develop new antioxidant biomaterials for preventing the onset of ROS‐related diseases. The materials’ morphology is detected by SEM analysis, whereas the chemical characterization is achieved by spectroscopic and spectrometric techniques. Despite an oxidation reaction in the quercetin structure, DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) and ABTS [2,2′‐azinobis‐(3‐ethylbenzothiazolin‐6‐sulfonic acid)] data show that all the materials preserve its antioxidant efficacy. MTT [3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide] test indicates a mild cytotoxicity in NIH‐3T3, PC12, and U251 cells. Furthermore, materials with the highest quercetin percentage are able to inhibit the H2O2‐induced intracellular ROS production in murine fibroblasts.

Influence of binary, ternary and quaternary mixtures on oxidative stability and study of kinetics and thermodynamic parameters of the degradation process of soybean biodiesel

Currently, studies show that plant extracts may exert antioxidant action and have aroused great interest because they have the property of preventing or minimizing the oxidative stress caused by free radicals. This study concerning to the binary, ternary and quaternary mixtures of plant extracts and the natural antioxidant quercetin with soybean biodiesel in concentrations ranging from (500 to 3000 ppm), using the acceletated oxidation techniques (Rancimat and PetroOXY), where the temperatures varied from 90 °C to 140 °C. The stabilizing factor was studied and indicated the existence of an antioxidant effect and not an antagonistic effect. Among the extracts the highest quantitative levels of flavonoids and total carotenoids were obtained in the following decreasing sequence: oregano extract (OE) > basil extract (BAE) > bilberry extract (BE), while for antioxidant activity front the DPPH radical the decreasing sequence was: oregano extract (OE) > bilberry extract (BE) > basil extract (BAE). The activation energies of the antioxidant mixtures were obtained by the Arrhenius equation and followed the ascending order: OEQC (62.69 kJ/mol) < BOBE (65.01 kJ /mol) < BAEQC (77.15 kJ/mol) < BEQC (77.73 kJ/mol) < BOBEQC (81.73 kJ /mol) by the technique Rancimat and BEQC (40.90 kJ/mol) < OEQC (41.82 kJ/mol) < BAEQC (42.32 kJ/mol) < BOBEQC (44.48 kJ/mol) < BOBE (45.31 kJ/mol) by the technique PetroOXY. The thermodynamic parameters ΔH* and ΔS*, were obtained by the Eyring equation and the ΔG* by the fundamental equation of thermodynamics, being evident, by the results shown, the existence of an endothermic and non-spontaneous process. The shelf life of antioxidant mixtures with biodiesel followed the descending order: BAEQC > BEQC > OEQC > BOBEQC > BOBE and OEQC > BAEQC > BEQC > BOBEQC > BOBE in the Rancimat and PetroOXY method, respectively. Therefore, the use of mixtures of these natural antioxidants was very promising and of fundamental importance in the control of the oxidative process of soybean biodiesel.

Novel eco-friendly “One-Pot” facile strategy for production of the natural quercetin from the plant: A model study

This work is aimed at the development of an “one-pot” technique for the production of the natural antioxidant quercetin (QR) from the buds of Sophora Japanese (Sophora japonica L.) using the subcritical water (SBW). For the first time, SBW that serves as a reactant and a solvent has been used to obtain QR in good yields starting from the buds of Sophora Japanese. High-performance liquid chromatography was used to determine the quantitative and qualitative compositions of the obtained products. For the first time, a new eco-friendly “one-pot” technique was proposed for production of QR from the buds of Sophora Japanese using SBW. This method of preparation of QR allows one to avoid the use of toxic organic solvents. The good yields of the targeted QR can be obtained for the period of time which is ten times shorter than needed by the traditional procedures.

A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models

BackgroundOsteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.ResultsPEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam.ConclusionThe present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin

The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe2+/AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant.

A Simple Way for the Preparation of Natural Antioxidant Quercetin from Rutin by Subcritical Water.

Context:Quercetin (QR) is a natural strong antioxidant of the plant origins. It is used for treating conditions of heart and blood vessels including “hardening of arteries” (atherosclerosis), high cholesterol, heart disease, circulation problems, preventing cancer, for treating chronic infections of the prostate, etc.,Aims:The aim of this work was to development and study of an acid-free technique for the preparation of QR from rutin (RT) that requires no use of acids and toxic organic solvents.Materials and Methods:For the first time, the subcritical water that serves as a reactant and a solvent were used to obtain QR in good yields starting from RT. High-performance liquid chromatography combined with mass spectrometry was used to determine the quantitative and qualitative compositions of the obtained products.Conclusions:For the first time, a new acid-free technique was used for the synthesis of natural antioxidant QR from an RT by subcritical water. That way requires no use of acids and/or toxic organic solvents. It has been shown that variation of only one parameter of the process (temperature of subcritical water) allows alteration to the composition of the hydrolysis products. The new method developed for the production of QR in subcritical water is environmentally friendly and faster than conventional hydrolysis methods that use acidic or enzymatic hydrolysis. The proposed technique has a potential for the future development of inexpensive and environmentally friendly technologies for the production of new pharmaceutical plant-based substances.

Heme Oxygenase-1 as a Novel Metabolic Player

Heme Oxygenase-1 as a Novel Metabolic Player

Quercetin Induces Mitochondrial Biogenesis through Activation of HO-1 in HepG2 Cells

The regeneration of mitochondria by regulated biogenesis plays an important homeostatic role in cells and tissues and furthermore may provide an adaptive mechanism in certain diseases such as sepsis. The heme oxygenase (HO-1)/carbon monoxide (CO) system is an inducible cytoprotective mechanism in mammalian cells. Natural antioxidants can provide therapeutic benefit, in part, by inducing the HO-1/CO system. This study focused on the mechanism by which the natural antioxidant quercetin can induce mitochondrial biogenesis in HepG2 cells. We found that quercetin treatment induced expression of mitochondrial biogenesis activators (PGC-1α, NRF-1, TFAM), mitochondrial DNA (mtDNA), and proteins (COX IV) in HepG2 cells. The HO inhibitor SnPP and the CO scavenger hemoglobin reversed the effects of quercetin on mitochondrial biogenesis in HepG2 cells. The stimulatory effects of quercetin on mitochondrial biogenesis could be recapitulated in vivo in liver tissue and antagonized by SnPP. Finally, quercetin conferred an anti-inflammatory effect in the liver of mice treated with LPS and prevented impairment of mitochondrial biogenesis by LPS in vivo. These salutary effects of quercetin in vivo were also antagonized by SnPP. Thus, our results suggest that quercetin enhances mitochondrial biogenesis mainly via the HO-1/CO system in vitro and in vivo. The beneficial effects of quercetin may provide a therapeutic basis in inflammatory diseases and sepsis.

Fanconi Anemia Links Reactive Oxygen Species to Insulin Resistance and Obesity

Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR.

Microwave-assisted synthesis and antioxidant properties of hydrazinyl thiazolyl coumarin derivatives.

BackgroundCoumarin derivatives exhibit a wide range of biological properties including promising antioxidant activity. Furthermore, microwave-assisted organic synthesis has delivered rapid routes to N- and O-containing heterocycles, including coumarins and thiazoles. Combining these features, the use of microwave-assisted processes will provide rapid access to a targeted coumarin library bearing a hydrazino pharmacophore for evaluation of antioxidant propertiesResultsMicrowave irradiation promoted 3 of the 4 steps in a rapid, convergent synthesis of a small library of hydrazinyl thiazolyl coumarin derivatives, all of which exhibited significant antioxidant activity comparable to that of the natural antioxidant quercetin, as established by DPPH and ABTS radical assaysConclusionsMicrowave dielectric heating provides a rapid and expedient route to a series of hydrazinyl thiazolyl coumarins to investigate their radical scavenging properties. Given their favourable properties, in comparison with known antioxidants, these coumarin derivatives are promising leads for further development and optimization.

Loss of Foxo3a In FA Mice Leads to Hematopoietic Stem Cell Exhaustion That Can Be Attenuated by Natural Anti-Oxidant Quercetin.

AbstractAbstract 1166Fanconi anemia (FA) is a genetic disorder characterized by genomic instability, bone marrow (BM) failure and predisposition to cancer. However, FA mouse models do not show spontaneous genetic instability. Previous study shows that FOXO3a is associated with the FA pathway through oxidative stress-specific interaction with FANCD2. To address the consequence of loss of FOXO3a function in FA hematopoiesis, we generated Foxo3a-/-Fancd2-/- and Foxo3a-/-Fancc-/- double-knockout (DKO) mice by crossing Foxo3a+/− with Fancd2+/− or Fancc+/−; mice. Reactive oxygen species are increased in low-density BM (LDBM) cells isolated from DKO mice compared to those from single KO (SKO) or wt mice. Analysis of hematologic parameters shows significantly increased number of nucleate cells and high ratio of eosinophils in peripheral blood of DKO mice. CFU assay shows more progenitor cells in peripheral blood isolated from DKO mice. Moreover, BM progenitor cells from DKO mice exhibit lower adhesion but higher migration activity, compared to those from wt or SKO mice. Consistent with this, Cdc42 pull-down assay shows lower Cdc42 activity in DKO LDBM cells than in wt or SKO cells, indicating that decreased Cdc42 may contribute to the observed aberrant adhesion and migration activities. DKO mice show significant decrease in primitive progenitor (Lin-Sca-1+c-kit+; LSK) cells, increase in BrdU+ and G1-phase LSK cells, and impaired repopulating capacity after competitive BM transplantation, which can be attenuated by the anti-oxidant Quercetin. Taken together, loss of Foxo3a in FA mice results in FA-like syndrome, which may be resulted from increased reactive oxygen species accumulation. Disclosures:No relevant conflicts of interest to declare.

Photostabilization Effect of Quercetin on the UV Filter Combination, Butyl Methoxydibenzoylmethane–Octyl Methoxycinnamate

The aim of the study was to investigate the effect of the natural antioxidant quercetin on the photostability of the most widely used combination of UVA (320-400 nm) and UVB (290-320 nm) filters, respectively butyl methoxydibenzoylmethane (BMDBM) and octyl methoxycinnamate (OMC). In order to reproduce the conditions prevalent in commercial sunscreen products, the stabilizing efficacy of quercetin was evaluated in model creams containing BMDBM (3%, wt/wt) together with OMC (4%, wt/wt) and exposed to a solar simulator at an irradiance corresponding to natural sunlight. Quercetin was found to enhance the photostability of the two UV filters in a concentration-dependent way. Addition of quercetin to the sunscreen formulation significantly reduced the photodegradation of BMDBM and OMC from 40.3 +/- 2.4 to 27.7 +/- 2.6% and from 51.3 +/- 2.1 to 42.2 +/- 2.0%, respectively. Moreover, comparative photodegradation studies demonstrated that quercetin was much more effective and at a lower concentration than commonly used stabilizer (octocrylene) and antioxidants (vitamin E, butylated hydroxyanisole). In vitro determination of the UVB and UVA protection parameters showed that the quercetin-based formulation fulfilled the official requirements on sunscreen products. Because of its photostabilizing and multiple antioxidant properties, quercetin represents a useful additive for the formulation of effective broad-spectrum sunscreens containing BMDBM and OMC.

The effects of the natural antioxidant quercetin and anions of the Hofmeister series on liposomes marked with chlorophyll a

The unilamellar liposomes of dimyristoylphosphatidylcholine (DMPC), marked with chlorophyll a (Chla), have been chosen as suitable models in studies aimed at determining the effects of natural antioxidant quercetin (QCT) and Hofmeister series anions on lipid bilayers. The variations of steady state fluorescence emission intensity of Chla have been recorded and the values of Chla fluorescence anisotropy, under constant temperature and viscosity, at pH = 7.3-7.4 have been measured. Two types of experiments have been performed. In the first type of experiment, the concentration of anions was maintained constant and the concentration of QCT was varied (from 0 to 100 micromol/l). In the second type of experiment, the concentration of QCT was constant (30 micromol/l) and the concentration of anions was varied (from 0 to 152 mmol/l). The quenching of Chla fluorescence by QCT pleads in favor of QCT insertion at interface water-lipid, in the vicinity of the polar heads of lipids from liposomal bilayer at physiological pH and temperature. Fluorescence anisotropy of Chla in liposomes brought more evidences for QCT localizations at lipid/water interface. Chla is sensing a more rigid microenvironment when QCT is added to the lipid bilayer and specific effects of the Hofmeister series anions.

Quercetin, a bioflavonoid, protects against oxidative stress-related renal dysfunction by cyclosporine in rats.

Nephrotoxicity is the most common and clinically important side effect of cyclosporine (CsA). Recent evidence suggests that reactive oxygen species (ROS) play an important role in CsA nephrotoxicity. This study was designed to demonstrate the role of oxidative stress and its relation to renal dysfunction and to investigate the effects of quercetin, a bioflavonoid with antioxidant properties, in CsA-induced nephrotoxicity. Quercetin (0.5 and 2.0 mg/kg i.p.) was administered 24 h before and concurrently with CsA (20 mg/kg s.c.) for 21 days. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS). Renal function was assessed by estimating plasma creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed histopathologically. Pretreatment with CsA (20 mg/kg s.c.) for 21 days produced elevated levels of TBARS and deteriorated renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle-treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. Quercetin (2 mg/kg) markedly reduced elevated levels of TBARS and significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. It is likely that quercetin, due to its antioxidant properties, prevented CsA-induced ROS and consequently CsA nephrotoxicity. These results clearly demonstrate the pivotal role of oxidative stress and its relation to renal dysfunction, and also point to the therapeutic potential of the natural antioxidant quercetin in CsA-induced nephrotoxicity.