Oxidation Of Thiol Groups Research Articles

Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy.

How to reduce the resistance of certain tumor cells to paclitaxel (PTX) and related taxoid anticancer drugs is a major challenge for improving cure rates. An oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX), which enhances drug efficacy and reverses resistance is thus designed. The mechanism involves diffusion of OPV-S-PTX into the cell, where π-π interactions lead to aggregation. Cross-linking of the aggregates via oxidation of thiol groups is favored in tumor cells because of the higher reactive oxygen species (ROS) concentration. Cross-linked aggregates "chemically lock" the multichromophore particle for a more persistent effect. The IC50 of OPV-S-PTX for tumor cell line A549 is reduced down to 0.33 × 10-9 m from that observed for PTX itself (41 × 10-9 m). Enhanced efficacy by OPV-S-PTX is proposed to proceed via acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice experiments reveal suppression of tumor growth upon OPV-S-PTX treatment. Altogether, these results show that the internal cross-linking of OPV-S-PTX through ROS provides a means to discriminate between tumor and healthy cells and the formation of the chemically locked particles enhances drug efficacy and helps in reducing resistance.

In Vitro Inhibitory Activity of Acca sellowiana Fruit Extract on End Products of Advanced Glycation.

IntroductionHyperglycemia plays an important role in the pathogenesis of diabetic complications, as it increases protein glycation, as well as the progressive accumulation of advanced glycation end products (AGEs), which are complex structures that produce fluorescence. The glycation reaction raises the levels of protein carbonyl, N ε-(carboxymethyl)lysine (CML), and fructosamine and decreases the level of thiol groups.MethodsIn the present study, the antiglycation activity was determined by fluorescence intensity using the bovine serum albumin (BSA)/glucose, CML method, and the level of fructosamine. The oxidation of proteins was determined by the carbonyl protein content and thiol groups.ResultsThe results show that the hexane extract of Acca sellowiana (FOH) at different concentrations (0.30–5 mg/ml) significantly inhibited the formation of AGEs in the BSA/glucose model during the 4 weeks of the study. FOH reduced the levels of fructosamine and CML. Our results showed a significant effect of FOH in the prevention of oxidative damage of proteins, as well as an effect on the oxidation of thiol groups and carbonyl proteins.ConclusionThe present study indicates that FOH is effective in inhibiting the glycation of proteins in vitro, so it can prevent or ameliorate the chronic conditions of diabetes associated with the formation of AGEs.

The role of CORM-2 as a modulator of oxidative stress and hemostatic parameters of human plasma in vitro.

PurposeThe main aim of the experiment is to examine the effect of CORM-2, a donor of carbon monoxide (CO), on oxidative stress in human plasma in vitro. In addition, it examines the effects of CORM-2 on the hemostatic parameters of plasma: the activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT).MethodsHuman plasma was incubated for 5–60 min with different concentrations of CORM-2: 0.1–100 μM. Following this, various hemostatic factors and biomarkers of oxidative stress were studied. Lipid peroxidation was measured as thiobarbituric acid reactive substance (TBARS) concentration, and the oxidation of amino acid residues in proteins was measured by determining the amounts of carbonyl and thiol groups.ResultsTwo oxidative stress inducers: hydrogen peroxide (H2O2) and the donor of hydroxyl radical (H2O2/Fe) were used. Decrease in protein carbonylation, thiol group oxidation and lipid peroxidation were detected at tested concentrations of CORM-2.ConclusionOur results indicate that CORM-2 may have antioxidant properties in human plasma treated with H2O2 or H2O2/Fe. In addition, our results indicate the anti-coagulant activities of CORM-2 in vitro.

Studies on reaction of glutathionylcobalamin with hypochlorite. Evidence of protective action of glutathionyl-ligand against corrin modification by hypochlorite.

Glutathionylcobalamin (GSCbl), a tight complex of glutathione (GSH) with cobalamin(III), is readily oxidized to aquacobalamin by hypochlorite. Corrin macrocycle remains unmodified in the presence of threefold excess of hypochlorite, whereas aqua- and cyanocobalamins are partially transformed to chlorinated species under the same conditions. The suggested mechanism of reaction between GSCbl and hypochlorite involves subsequent oxidation of thiol and amino groups and dissociation of oxidized glutathione from Co(III)-ion.

3-Nitro-2-pyridinesulfenates as Efficient Solution- and Solid-Phase Disulfide Bond Forming Agents.

In this paper, a new disulfide-forming agent based on the finding that alkoxy 3-nitro-2-pyridinesulfenates (Npys-OR) can oxidize thiol groups is reported. Methyl 3-nitro-2-pyridinesulfenate (Npys-OMe), which is easily prepared from 3-nitro-2-pyridinesulfenyl chloride in a one-step reaction and has a reduction peak potential (Epc ) of -0.541 V versus Ag/AgCl, produces the cyclic nonapeptide oxytocin from its linear form in good yield (92 %) with minimal oligomer formation. Npys-OMe in the solid phase also demonstrated excellent results in oxytocin synthesis. Other disulfide-containing peptides, such as α-human atrial natriuretic peptide and α-conotoxin ImI, were also successfully synthesized. During these syntheses, no side reactions of methionine (Met) and tryptophan (Trp) residues or the S-acetamidomethyl (Acm) protecting group were detected. These results suggested that Npys-OMe or its solid-phase analog provides a new strategy for regioselective disulfide bond formation to assist the synthesis of complex disulfide-rich peptides.

Markers of oxidative/nitrative damage of plasma proteins correlated with EDSS and BDI scores in patients with secondary progressive multiple sclerosis

ABSTRACTObjectives: The objective of the present study was to evaluate oxidative/nitrative stress in the plasma of 50 patients suffering from the secondary progressive course of multiple sclerosis (MS), and to verify its correlation with physical and mental disability as assessed by the Expanded Disability Status Scale (EDSS), and the Beck Depression Inventory (BDI).Methods: Oxidative and nitrative damage to proteins was determined by the level of carbonyl groups and 3-nitrotyrosine using ELISA test. Based on the reaction with Ellman’s reagent, we estimated the concentration of oxidized thiol groups. Additionally, we measured the level of lipid peroxidation.Results: In plasma drawn from MS patients, we observed a significantly higher level of 3-NT (92%; P < 0.0003), carbonyl groups (29%; P < 0.0001) and thiobarbituric acid reactive substances (73%; P < 0.0001), as well as a lower concentration of thiol groups (33%; P < 0.0001), in comparison to healthy subjects. We noted positive correlations between the level of carbonyl groups or 3-NT and both diagnostic parameters, EDSS and BDI. Negative correlations were observed between concentration of -SH groups and EDSS and BDI.Conclusion: Our results indicate that impaired red-ox balance can significantly promote neurodegeneration in secondary progressive MS.

Surface-anchored counterions on weak chiral anion-exchangers accelerate separations and improve their compatibility for mass-spectrometry-hyphenation

In the present work we propose new variants of chiral stationary phases (CSP) with tert-butylcarbamoylquinine (tBuCQN) as chiral selector molecule. Four tBuCQN-CSPs with distinct bonding chemistries are compared in terms of their pH-dependent surface charge by ζ-potential determinations, by achiral and chiral liquid chromatographic tests and LC–ESI–MS hyphenation. In one embodiment tBuCQN was immobilized on 3-mercaptopropylmethylsilyl-modified silica by thiol-ene click reaction (brush type CSP with selector coverage of 0.38mmol/g). In another embodiment, poly-(3-mercaptopropyl)-methylsiloxane was coated onto vinylized silica particles in presence of tBuCQN and radical initiator. The tBuCQN selector was then immobilized onto the polysiloxane film which in turn was crosslinked to the vinyl-surface in a simultaneous double click reaction leading to a CSP with enhanced stability due to multiple linkages (0.29mmol/g tBuCQN). Aliquots of each of the two CSPs were further modified by oxidation of free residual thiol groups to sulfonic acid functionalities to obtain strongly acidic endcapping groups which act as immobilized counterions of the chiral WAX CSPs (0.2mmol/g sulfonic acid co-ligands for brush type CSP). This caused secondary repulsive interactions, hence balanced interactions of the target analytes (chiral acids) at the WAX site and decreased non-specific interactions. Furthermore, this rendered possible the use of milder elution conditions, i.e. lower ionic strength, for acidic compounds. Separation performance was maintained and slightly improved, respectively, when using polar organic or reversed-phase type elution mode in chiral separations which were significantly accelerated (isoeluotropic conditions could be achieved with ca. factor 40 lower counterion concentration in the mobile phase). Thus, LC–ESI–MS enantiomer separations could be readily performed at very low ionic strength conditions (10mM acetate) which is favorable due to less ion suppression. In addition to this the newly developed stationary phases showed complementary retention profiles in RP- and HILIC-mode which make these type of stationary phases also promising tools for achiral applications in pharmaceutical analysis, especially as orthogonal separation principle e.g. in 2D-LC and impurity profiling.

Elemental labelling and mass spectrometry for the specific detection of sulfenic acid groups in model peptides: a proof of concept

Oxidative transformation of cysteine thiol groups into different functional groups is considered a significant posttranslational modification of great importance in pathological and physiological processes. A cysteine sulfenic acid (SA) residue is the transient state for thiol group oxidation and it can react with free thiols to form disulfide bonds or can be further oxidized with reactive oxygen/reactive nitrogen species (ROS/RNS) to form sulfinic and sulfonic acids. The increase in ROS/RNS concentrations is correlated to age-related diseases such as cancer and Alzheimer's disease. Since the formation of SA represents a transient state of oxidation of thiols, its formation can be considered a redox-sensitive sensor for the presence of ROS/RNS. Thereby, the detection of the short-lived SA will provide greater insight into the redox-mediated events that alter the structure and function of peptides and proteins. The aim of this study is to provide a new strategy for the highly sensitive and specific detection of SA in peptides as a proof of concept. For this aim, SA was firstly generated in model peptides on oxidation with H2O2 and then captured by the linear alkyne β-ketoester (KE) previously linked to a lanthanide (Ln)-containing chelator (Ln-DOTA, where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The linking of the KE to DOTA was performed by click chemistry, resulting in a new reagent (Ln-DOTA-KE) that permits highly sensitive elemental (inductively coupled plasma) and molecular (electrospray) mass spectrometric detection. The new reagent (Ln-DOTA-KE) reacts specifically with SA, offering improved reactivity at physiological pH, facile derivatization and a cell-membrane-permeable compound that has promising future applications. Graphical Abstract A new derivatizing reagent for specific detection of sulphenic acid (SA) generated in model peptides by oxidation of cysteine groups is presented in this work.

Evaluation of antioxidant activity of phenolic fractions from the leaves and petals of dandelion in human plasma treated with H2O2 and H2O2/Fe

Taraxacum officinale (dandelion) is a widespread perennial of the Asteraceae family. Dandelion is a rich source of different bioactive compounds, including phenolic compounds, terpenes, carbohydrates, proteins, fatty acids, vitamin and minerals. However, the content of phenolics in tested extracts by various authors was not always well described. Dandelion is also a commonly available food with a long history of human use and as such poses little risk of harm. In this study, we focused on four different phenolic fractions from leaves and petals of dandelion, which might be of great interest. The objective was to investigate the antioxidant properties of the phenolic fractions from dandelion leaves and petals in vitro. Effects of four different phenolic fractions from dandelion leaves and petals on the production of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) in human plasma were studied in vitro. Their antioxidant properties against human plasma protein carbonylation and oxidation of protein thiols induced by a strong biological oxidant – hydrogen peroxide (H2O2) or H2O2/Fe (a donor of hydroxyl radicals) were also examined. The tested fractions of dandelion (0.5–50 μg/mL; the incubation time – 30 min) inhibited plasma lipid peroxidation induced by H2O2 or H2O2/Fe. However, their antioxidant properties were not concentration-dependent. All tested samples also inhibited plasma protein carbonylation and oxidation of thiol groups in plasma proteins stimulated by oxidants (H2O2 and OH∙). The obtained results suggest that four tested dandelion fractions, especially phenolic fractions from petals which are recognized as better than leaves source of flavonoids, may be a new and promising source of natural compounds with antioxidant activity beneficial for diseases-associated with oxidative stress, and with changes of hemostasis.

Salicylic acid induces the proton conductance in the inner mitochondrial membrane of lupine cotyledons

The influence of salicylic acid (SA) on generation of membrane potential (Δψ) at the inner membrane of isolated mitochondria from cotyledons of lupine seedlings (Lupinus angustifolius L.) was investigated. The mitochondrial preparations conformed to all criteria of the intactness: the organelles were characterized by the integrity of their membranes and by tight coupling of oxidation and phosphorylation. High functional activity of mitochondria was also evident from their ability to generate Δψ during succinate oxidation and from the long-term maintenance of steady-state transmembrane potential by virtue of electrontransport chain (ETC) operation or ATP hydrolysis after the inhibition of respiratory ETC. The addition of SA to the incubation medium (0.5–1.0 mM) induced a fast and complete dissipation of Δψ after a distinct lag period. The Δψ was not restored by subsequent ATP hydrolysis, indicating that the phytohormone SA induced the proton conductance of the inner membrane. The SA-induced collapse of Δψ was observed under suppression of ETC by anaerobiosis, cyanide, or inhibitory concentrations of the phytohormone. The SAinduced dissipation of Δψ was not reversed by cyclosporine A but was prevented in the presence of dithiothreitol (DTT). Conversely, the incubation of mitochondria in the presence of phenylarsine oxide (PAO) known to oxidize the protein thiol groups also elevated the proton conductance and eliminated Δψ at the inner membrane of lupine mitochondria. The PAO-induced Δψ collapse was not reversed in the presence of ATP, but Δψ was restored after the addition of DTT. These results and the literature data suggest that, under suppressed ETC activity, salicylic acid permeabilizes the inner membrane of mitochondria from cotyledons of lupine seedlings due to opening of a specialized mitochondrial uncoupling channel (MUC) that is permeable to protons and, possibly, to other small cations (K+, Ca2+). An important role in the induction of MUC belongs apparently to oxidative stress resulting in oxidation of thiol groups in protein molecules that constitute this channel or regulate the channel activity.

Oxidation of cell surface thiol groups by air-oxidized terpenes triggers activation of Nrf2

Oxidation of cell surface thiol groups by air-oxidized terpenes triggers activation of Nrf2

Understanding Interactions between Cellular Matrices and Metal Complexes: Methods To Improve Silver Nanodot‐Specific Staining

Metal complexes are frequently used for biological applications due to their special photophysical and chemical characteristics. Due to strong interactions between metals and biomacromolecules, a random staining of cytoplasm or nucleoplasm by the complexes results in a low signal-to-background ratio. In this study, we used luminescent silver nanodots as a model to investigate the major driving force for non-specific staining in cellular matrices. Even though some silver nanodot emitters exhibited excellent specific staining of nucleoli, labeling with nanodots was problematic owing to severe non-specific staining. Binding between silver and sulfhydryl group of proteins appeared to be the major factor that enforced the silver staining. The oxidation of thiol groups in cells with hexacyanoferrate(III) dramatically weakened the silver-cell interaction and consequently significantly improved the efficiency of targeted staining.

Spray-dried mucoadhesives for intravesical drug delivery using N-acetylcysteine- and glutathione-glycol chitosan conjugates.

This work describes N-acetylcysteine (NAC)- and glutathione (GSH)-glycol chitosan (GC) polymer conjugates engineered as potential platform useful to formulate micro-(MP) and nano-(NP) particles via spray-drying techniques. These conjugates are mucoadhesive over the range of urine pH, 5.0-7.0, which makes them advantageous for intravesical drug delivery and treatment of local bladder diseases. NAC- and GSH-GC conjugates were generated with a synthetic approach optimizing reaction times and purification in order to minimize the oxidation of thiol groups. In this way, the resulting amount of free thiol groups immobilized per gram of NAC- and GSH-GC conjugates was 6.3 and 3.6mmol, respectively. These polymers were completely characterized by molecular weight, surface sulfur content, solubility at different pH values, substitution and swelling degree. Mucoadhesion properties were evaluated in artificial urine by turbidimetric and zeta (ζ)-potential measurements demonstrating good mucoadhesion properties, in particular for NAC-GC at pH 5.0. Starting from the thiolated polymers, MP and NP were prepared using both the Büchi B-191 and Nano Büchi B-90 spray dryers, respectively. The resulting two formulations were evaluated for yield, size, oxidation of thiol groups and ex-vivo mucoadhesion. The new spray drying technique provided NP of suitable size (<1μm) for catheter administration, low degree of oxidation, and sufficient mucoadhesion property with 9% and 18% of GSH- and NAC-GC based NP retained on pig mucosa bladder after 3h of exposure, respectively. The aim of the present study was first to optimize the synthesis of NAC-GC and GSH-GC, and preserve the oxidation state of the thiol moieties by introducing several optimizations of the already reported synthetic procedures that increase the mucoadhesive properties and avoid pH-dependent aggregation. Second, starting from these optimized thiomers, we studied the feasibility of manufacturing MP and NP by spray-drying techniques. The aim of this second step was to produce mucoadhesive drug delivery systems of adequate size for vesical administration by catheter, and comparable mucoadhesive properties with respect to the processed polymers, avoiding thiolic oxidation during the formulation. MP with acceptable size produced by spray-dryer Büchi B-191 were compared with NP made with the apparatus Nano Büchi B-90.

Mechanisms of Oxidative Stress an d Vessels Sclerotic Transformation Initiated by Uremic Toxin Indoxyl Sulfate

&lt;p&gt; The microspherical carbonaceous adsorbents SCN and AST-120 for oral use prevent chronic disease progression, delay dialysis initiation, lessen atherosclerosis development in kidney and decreased of overall and cardiovascular mortality. This therapeutic effect is due to the binding of indole by sorbents in large intestine, which is a precursor of indoxyl sulfate (IS). It is considered that IS accelerates the progression of chronical kidney disease (CKD) by inducing a formation of reactive oxygen species (ROS) and promotes aortic calcification (mineralization). Molecular mechanisms of IS action is unknown. Using density functional theory calculations in the frames of B3LYP exchange and correlation functional (basis set 6-311G) and solvation accounting on the base of polarizable continuum model (PCM) we have studied some chemical transformations of IS and have shown a possibility of indoxyl sulfate and hydroperoxyl radicals formation through the reaction of IS with endogenous singlet oxygen. Due to the high activity indoxyl sulfate radicals initiate uncontrollable processes of oxidative stress (OS) in kidney and vascular tissues that promote a development of CKD. We also proposed a hypothesis, which can explain the role of OS in the accelerated development of sclerosis (vessels mineralization) in patients with renal diseases. In particular it was hypothesized and then supported by B3LYP/6-311G(d) + PCM calculations that sulfonic groups (products of deep oxidation of thiol groups in tissue proteins under OS, induced by IS) can selectively bind of Ca&lt;sup&gt;2+&lt;/sup&gt; ions and, consequently, forming RSO&lt;sub&gt;3&lt;/sub&gt;Ca&lt;sup&gt;+&lt;/sup&gt; groups which can fix НРО&lt;sub&gt;4&lt;/sub&gt;&lt;sup&gt;2ˉ&lt;/sup&gt; and CO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;2ˉ&lt;/sup&gt; anions. The products of anions fixation can then bind of Ca2+ ions, etc. Notably, these processes are, probably, primary starting point in case of sclerotic vessel changes. The beginning of this starting mineralization process most likely is possible with proteins carboxyl groups forming under OS that also can bind Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;/p&gt;

Sulfonic functionalized SBA-15 catalysts in the gas phase glycerol dehydration. Thermal stability and catalyst deactivation

The catalytic conversion of glycerol to acrolein was studied using sulfonic functionalized mesoporous silica SBA-15. The catalysts were prepared by the co-condensation method, conducting the silica synthesis and functionalization of its surface with thiol-propyl groups in the same stage. In a next step, the oxidation of thiol groups to sulfonic groups was made varying the concentration of H2O2 in order to obtain catalysts with different levels of acidity on the surface. The solids were characterized by BET, SEM, FTIR, XPS, and potentiometric titration with n-butilamine. The thermal stability was analyzed by thermogravimetry (TGA) and temperature-programmed desorption (TPD). The reaction tests were performed at different temperatures between 275 °C and 350 °C, and under feed flow conditions that allowed the study of the deactivation phenomena by coke deposition. The best temperature in order to maximize the acrolein yield was 300 °C. Higher temperatures led to a rapid deactivation by a combined effect of coke deposition and decomposition of functional groups.

Malfunctions of the conjugated system “Restoring thiols – Nitrogen oxide” with acute cerebrovascular accident and possible correction

&lt;p&gt;Experimental acute ischemic stroke was modeled by bilateral occlusion of the common carotid arteries in rats. Antioxidant system in the brain tissue was evaluated by the activity of key enzymes of thiol and disulfide indicators&lt;br /&gt;nitrosative stress. Simulation of acute ischemic accompanied by violation of the thiol-disulfide balance and increased nitrotyrosine levels, indicating that the development of oxidative and nitrosative stress in brain tissue. It is established&lt;br /&gt;that the use of thiol-containing antioxidants – Thiotriazoline and Angiolin set the highest possible ratio between the levels of reduced and oxidized thiol groups and glutathione, which indicates that the active mobilization of thioldisulfide&lt;br /&gt;system in the neutralization products of free-radical oxidation. Identified effects of the drugs used due to the presence in their structure of the thiol group, which contributes to the normalization of the glutathione system in conditions of oxidative stress.&lt;/p&gt;

The effect of radiation-induced reactive oxygen species (ROS) on the structural and functional properties of yeast alcohol dehydrogenase (YADH)

Purpose: To determine the mechanism underlying oxidative modifications caused by radiation-induced reactive oxygen species (ROS) and elucidate their effect on the structure and function of yeast alcohol dehydrogenase (YADH), a zinc-containing protein.Materials and methods: YADH was exposed to water radiolysis products in an air atmosphere. YADH oxidation products were determined by spectrophotometric and spectrofluorimetric methods. The extent to which oxidative modifications affected enzyme activity was also studied.Results: Water radiolysis products oxidized thiol groups leading to the release of zinc ions and the destruction of tryptophan and tyrosine residues. Those processes were accompanied by alterations in protein structure such as increased surface hydrophobicity, greater tryptophan accessibility to acrylamide, and changes in the secondary structure. Structural modifications were correlated with lower enzyme activity.Conclusion: During the process of functional and structural changes in YADH exposed to reactive oxygen species, a key part is the oxidation of cysteine residues attached to zinc and the release of zinc ions from the molecule. It may be assumed that ROS induce similar changes in many other zinc-containing proteins.

Water electrolyte promoted oxidation of functional thiol groups

The formation of disulfide bonds is of the utmost importance for a wide range of food products with gluten or globular proteins as functional agents. Here, the impact of mineral electrolyte composition of aqueous solutions on thiol oxidation kinetics was studied, using glutathione (GSH) and cysteine (CYS) as model systems. Interestingly, the oxidation rate of both compounds into their corresponding disulfides was significantly higher in common tap water than in ultrapure water. The systematic study of different electrolyte components showed that especially CaCl2 improved the oxidation rate of GSH. However, this effect was not observed for CYS, which indicated a strong impact of the local chemical environment on thiol oxidation kinetics.

Nitroxides protect against peroxynitrite-induced nitration and oxidation

Nitroxides are promising compounds for prevention of undesired protein modifications. The aim of this study was to compare the efficiency of 11 nitroxides, derivatives of 2,2,6,6-tetramethylpiperidine-1-oxide (TEMPO) and 2,2,5,5-tetramethylpirrolidine-1-oxyl (PROXYL) in prevention of nitration and oxidation of model compounds and human serum albumin (HSA). Most nitroxides were very efficient in preventing loss of fluorescein fluorescence induced by peroxynitrite (PN) (IC50 in the nanomolar range) and preventing HSA nitration. The loss of fluorescein fluorescence was demonstrated to be due to nitration. Nitroxides were more effective in prevention nitration than oxidation reactions. They showed a concentration window for preventing dihydrorhodamine (DHR) 123 oxidation but exerted a prooxidant effect at both high and low concentrations. No prooxidant effect of nitroxides was seen in prevention of DHR123 oxidation induced by SIN-1. In all essays hydrophobic nitroxides (especially 4-nonylamido-TEMPO and 3-carbamolyl-dehydroPROXYL) showed the lowest efficiency. An exception was the prevention of thiol group oxidation by PN and SIN-1 where hydrophobic nitroxides were the most effective, apparently due to binding to the protein. Nitroxides showed low toxicity to MCF-7 cells. Most nitroxides, except for the most hydrophobic ones, protected cells from the cytotoxic action of SIN-1 and SIN-1-induced protein nitration. These results point to potential usefulness of nitroxides for prevention of PN-induced oxidation and, especially, nitration.

Dill tablet: A potential antioxidant and anti-diabetic medicine

ObjectiveTo evaluate the antiglycation and antioxidant properties of the dill tablet, an herbal product used in Iran as a hypolipidemic medicine. MethodsIn this descriptive study, the antioxidant and antiradical properties of dill tablet at different concentration (0.032, 0.065, 0.125, 0.25, 0.5 and 1 mg/mL) were measured. The total phenolic, flavonols and flavonoid, alkaloids, anthocyanin, tannin and saponin contents in dill tablet were determined. Furthermore, antiglycation properties of dill tablet were assayed. In the in vivo experiments, male rats were randomly divided into three groups (n = 6): Group 1: normal rats; Group 2: diabetic rats; Group 3: diabetic rats + 300 mg/kg dill tablet, and Group 4: diabetic rats + 100 mg/kg dill tablet. After 2 months, the blood glucose was measured enzymatically and advanced glycation end-products (AGEs) formation was determined using a fluorometric method. ResultsOur results illustrated that different concentrations of dill tablet had significant antioxidant activity. Dill tablet markedly declined AGEs formation and fructosamine levels (P < 0.001) compared with glycated sample. Oxidation of protein carbonyl and thiol group was significantly reduced by dill tablet in a dose dependent manner (P < 0.001). Formation of amyloid cross-β and fragmentation were markedly inhibited by dill tablet (P < 0.001) compared with glycated sample. After 2 months, fasting blood glucose levels (P < 0.001) and AGEs formation (P < 0.05) were significantly reduced by dill tablet in diabetic animals. ConclusionsDill tablet exhibited significant antiglycation and antioxidant activities. This study provides a scientific basis for using dill in treatment of diabetic patients.