Water-soluble Analogue Of Vitamin Research Articles

Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives

The redox balance plays a crucial role in maintaining biological processes under normal conditions. Antioxidants inhibit and reduce harmful oxidation processes, while pro-oxidants can act as anti-cancer agents by promoting ROS-mediated cell death. The aim of this study is to compare the redox properties of seven newly synthesised tribromopyrrole derivatives with three novel and four previously synthesized non-halogenated analogues in an in vitro model (in human serum) and with exogenously induced oxidative stress. The obtained values of their oxy scores (OS) were compared and the result showed that four non-halogenated pyrrole derivatives with secondary amide group M2, M10, M11 and M12 have lower OS values than Trolox, a water-soluble analogue of vitamin E with proven antioxidant properties. All four compounds show strong resistance to oxidative stress, which is reflected in the maintenance of negative OS values when exposed to exogenous oxidative stress using TBH in the reaction mixture. This capability to resist invading ROS should be expected also in an endogenous environment, where constant prooxidant production takes place at a low, homeostatic level, but even more so in pathological conditions. The tribrominated derivative M15 showed prooxidant activity with a significantly higher OS value than all other compounds tested. The comparison of the dose-response of Trolox and the five compounds with the lowest OS also shows that compounds M2, M7 and M10 have better antioxidant activity than Trolox.

PLA-PEG-Cholesterol biomimetic membrane for electrochemical sensing of antioxidants

Polymeric membranes exhibit unique and modulate transport properties when they are properly functionalised, which make them ideal for ions transport, molecules separation and molecules interactions. The present work proposes the design and fabrication of nanostructured membranes, composed by biodegradable poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), incorporating a lipophilic molecule (cholesterol) covalently bonded, were especially designed to provide even more application opportunities in sensors field. Electrochemical studies, by means of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV), revealed important differences regarding the functionalised and non-functionalised PLA systems. PEG-cholesterol building block units showed a clear affinity with ascorbic acid (vitamin C) and Trolox® (a water-soluble analogue of vitamin E), both hydrophilic in nature, with a limit of detection capacity of 8.12 µM for AA and 3.53 µM for AA and Trolox, respectively, in aqueous salt solution. The bioinspired polymer may be used to incorporate antioxidant property that allow the design of anti-stress biosensors, electrodes for the detection of vitamin C or vitamin E in biomedical nutrition programs, among other applications.

Antioxidant Activity of Conjugates of Cerium Dioxide Nanoparticles with Human Serum Albumin Isolated from Biological Fluids

For the first time, an analysis was made of the antioxidant properties of conjugates of CeO2 nanoparticles with human serum albumin (CeO2@HSA), including HSA isolated from blood plasma and biological fluids similar in composition to blood plasma, namely, peritoneal (ascitic) and synovial (articular) fluids. The antioxidant activity of hybrid nanomaterials was studied in relation to alkylperoxyl radicals by luminol-dependent chemiluminescence. It was shown that the interaction of CeO2 nanoparticles with purified human serum albumin is accompanied by a decrease in the antioxidant and prooxidant potential of albumin by a factor of ⁓1.5. Presumably, this is caused by the interaction of nanodispersed CeO2 with sulfhydryl groups of the protein. Conjugates of CeO2 nanoparticles with albumin isolated from biological fluids (CeO2@HSA) exhibit a synergistic antioxidant effect. In this case, the mechanism of antioxidant activity is fundamentally different from that for CeO2 sols modified with purified human serum albumin. According to quantitative assessment, the antioxidant capacity of CeO2@HSA conjugates is ⁓20 times lower than that of Trolox, a water-soluble analog of vitamin E.

Trolox Antioxidant as a Factor in Stabilization of Human Cord Blood Nucleated Cells During Cryopreservation

The paper presents experimental data on the determination of preservation rate of human cord blood nucleated cells and their apoptosis/necrosis stages to determine the number of viable functionally active cells after cryopreservation in solutions with different concentrations of DMSO and the water-soluble analogue of vitamin E, the antioxidant trolox. Counting the number of human cord blood nucleated cells after freezing in media with the addition of trolox revealed their maximum preservation in the samples with 7.5% DMSO and 50, 70 or 200 μM of the antioxidant. Using the flow cytometry with the addition of the Annexin V FITC reagent, which specifically binds to phospholipids, and the DNA dye 7-amino-actinomycin D (7-AAD), it was established that trolox in concentrations of 50–70 μM provided an increase in the number of viable cells with intact membrane (AnnexinV─/7AAD─) by 12–16% compared to the control, which involved the use of only DMSO in the cryoprotective solution. The obtained results indicate the effectiveness of using the antioxidant trolox and the prospects of developing trolox-containing cryoprotective mixtures for freezing and long-term storage of nucleated cord blood cells, including hematopoietic progenitor cells.

Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson's Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment.

Trolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1β-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms of Trolox against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of trolox against neuroinflammation, the oxidative stress mediated by MPTP in the Parkinson's disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25-30 g). Our study showed that MPTP increased the expression of α-synuclein, decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, Trolox treatment significantly reversed these PD-like pathologies. Furthermore, Trolox treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Lastly, Trolox treatment inhibited the activated astrocytes (GFAP) and microglia (Iba-1), also reducing phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Overall, our study demonstrated that Trolox may exert neuroprotection on dopaminergic neurons against MPTP-induced oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration.

Effect of Changes in the Redox Status on Biofilm Formation in Escherichia coli.

Changes in the redox balance in the medium and in Escherichia coli cells significantly affect the ability of bacteria to form biofilms. An increase in the level of aeration in the culture of wild-type bacteria led to a 3-fold decrease in the mass of biofilms. Mutants lacking components of the glutathione and thioredoxin redox systems, as well as transporters involved in the transmembrane cycling of glutathione, demonstrated increased biofilm formation ability. The effect of exogenous glutathione on biofilm formation depended on the culturing conditions. The addition of 0.1-1 mM Trolox (a water-soluble analog of vitamin E) was accompanied by a 30-40% reduction in biofilm formation.

Novel Hybrid Indole-Based Caffeic Acid Amide Derivatives as Potent Free Radical Scavenging Agents: Rational Design, Synthesis, Spectroscopic Characterization, In Silico and In Vitro Investigations

Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A multiple-step scheme of in vitro radical scavenging assays was carried out to evaluate the antioxidant activity of the synthesized compounds. The results of the DPPH assay demonstrated that the indole-based caffeic acid amides are more active free radical scavenging agents than their benzamide analogues. Compared to Trolox, a water-soluble analogue of vitamin E, compounds 3a, 3f, 3h, 3j, and 3m were found to have excellent DPPH radical scavenging activities with IC50 values of 95.81 ± 1.01, 136.8 ± 1.04, 86.77 ± 1.03, 50.98 ± 1.05, and 67.64 ± 1.02 µM. Three compounds out of five (3f, 3j, and 3m) showed a higher capacity to neutralize the radical cation ABTS•+ more than Trolox with IC50 values of 14.48 ± 0.68, 19.49 ± 0.54, and 14.92 ± 0.30 µM, respectively. Compound 3j presented the highest antioxidant activity with a FRAP value of 4774.37 ± 137.20 μM Trolox eq/mM sample. In a similar way to the FRAP assay, the best antioxidant activity against the peroxyl radicals was demonstrated by compound 3j (10,714.21 ± 817.76 μM Trolox eq/mM sample). Taken together, compound 3j was validated as a lead hybrid molecule that could be optimized to maximize its antioxidant potency for the treatment of oxidative stress-related diseases.

Abstract 15024: High Concentration Mineral Oil, Corn Oil and Their Constitutive Fatty Acids Do Not Influence Low-Density Lipoprotein (LDL) Oxidation Rates in vitro

Introduction: LDL transports dietary long chain fatty acids, constituents that may influence rates of lipid oxidation. Modified LDL promotes foam cell formation during atherosclerosis. The omega-3 fatty acid (n3-FA) eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE), reduced cardiovascular events in REDUCE-IT compared to mixed n3-FAs in similar high-risk patients (STRENGTH). Some have attributed these discordant outcomes, in part, to placebo choice (mineral versus corn oil) despite very limited oral absorption. We compared the effects of these oils and various FAs on rates of LDL oxidation at supra-pharmacologic doses. Methods: LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL before being incubated at 37°C for 30 min with pharmaceutical grade mineral or corn oil at high concentrations (100 μg/mL) that are comparable to treatment achieved n3-FAs (4 g/d) that have high oral absorption. We also tested FAs contained in these oils, including stearic acid (18:0), arachidic acid (20:0), and linoleic acid (18:2, n-6) as well as ascorbic acid (10 μM) and a water-soluble analog of vitamin E (Trolox, 10 μM) as controls. All samples then underwent copper-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Results: MDA formation increased from 0.28 ± 0.03 to 9.96 ± 0.58 μM ( p <0.001) with vehicle treatment from 0-2 h. Addition of either mineral or corn oil at 100 μg/mL did not significantly influence rates of MDA formation at 2 h (0.02% and 1.93% change vs vehicle, respectively). Nor did we observe any antioxidant activity with constituent FAs stearic acid, arachidic acid, or linoleic acid, FAs with no or two double bonds. As antioxidant controls, ascorbic acid and Trolox both reduced LDL oxidation by 93% and 94% (0.71 ± 0.11 and 0.62 ± 0.04 to 9.96 ± 0.58 μM, p <0.001) after 2 h. Conclusions: Neither mineral nor corn oils affected LDL oxidation even at supra-pharmacologic concentrations. Beyond poor oral absorption, mineral oil and its constituent fatty acids did not affect LDL oxidation, a property related to mechanisms of atherosclerosis.

Synthesis and antioxidant activities of benzylic bromophenols inclusive of natural products.

The synthesis of natural products 2-(2,3-dibromo-4,5-dihydroxyphenyl)acetic acid (1) and 2-(2,6-dibromo-3,5-dihydroxyphenyl)acetic acid (2) and as well as their derivatives 25 and 26 were carried out by substitution, hydrolysis and demethylation reactions of the corresponding four benzyl bromides. The antioxidant potentials of benzylic acid-derived bromophenols were, for the first time, appraised by several outstanding bioanalytical methods. Besides these, we estimated the antioxidant effects which were studied using the methods of DPPH·, ABTS•+ scavenging activities, ferric (Fe3+) and cupric (Cu2+) ions and Fe3+-TPTZ reducing capacities. Benzylic acid-derived bromophenols were found as effective DPPH•, and ABTS•+ scavengers. The potential antioxidant activities of bromophenol derivatives 1, 2 and 17-28 were compared to standard antioxidants including BHA, BHT, α-Tocopherol, and Trolox, which is a water-soluble analog of vitamin E. We expect that this innovative work will direct future studies exploring the antioxidant properties of food, medicinal, and industrial applications.

Tunneling in the Hydrogen-Transfer Reaction from a Vitamin E Analog to an Inclusion Complex of 2,2-Diphenyl-1-picrylhydrazyl Radical with β-Cyclodextrin in an Aqueous Buffer Solution at Ambient Temperature.

Recently, increasing attention has been paid to quantum mechanical behavior in biology. In this study, we investigated the involvement of quantum mechanical tunneling in the hydrogen-transfer reaction from Trolox, a water-soluble analog of vitamin E (α-tocopherol), to 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) in a phosphate buffer solution (0.05 M, pH 7.0). DPPH• was used as a reactivity model of reactive oxygen species and solubilized in water using β-cyclodextrin (β-CD). The second-order rate constants, kH and kD, in 0.05 M phosphate buffer solutions prepared with H2O (pH 7.0) and D2O (pD 7.0), respectively, were determined for the reaction between Trolox and DPPH•, using a stopped-flow technique at various temperatures (283–303 K). Large kinetic isotope effects (KIE, kH/kD) were observed for the hydrogen-transfer reaction from Trolox to the β-CD-solubilized DPPH• in the whole temperature range. The isotopic ratio of the Arrhenius prefactor (AH/AD = 0.003), as well as the isotopic difference in the activation energies (19 kJ mol−1), indicated that quantum mechanical tunneling plays a role in the reaction.

Novel Extract from Beetle Ulomoides dermestoides: A Study of Composition and Antioxidant Activity.

A biologically active extract from the darkling beetle Ulomoides dermestoides was obtained using the electro-pulse plasma dynamic extraction method. The beetle water extract contained a complex of antioxidant substances such as antioxidant enzymes and nonprotein antioxidants, as well as a complex of heat shock antistress proteins. This determines the rather high antioxidant activity of the aqueous extract of the beetle, i.e., 1 mg of dry matter/mL of the extract has an equivalent antioxidant activity to 0.2 mM Trolox (a water-soluble analog of vitamin E). It was shown that the beetle extract can lead to a 25–30% increase in the average lifespan of nematode Caenorhabditis elegans, under normal conditions, and a 12–17% increase under conditions of oxidative stress (with paraquat), and significantly inhibits the fructosylation reaction of serum albumin. Therefore, the beetle aqueous extract shows promise as a biologically active complex exhibiting antioxidant activity.

Quantification of Free Radical Scavenging Properties and SOD-Like Activity of Cerium Dioxide Nanoparticles in Biochemical Models

The enhanced chemiluminescence method in combination with mathematical modeling has been used to quantify the antioxidant properties and to study the superoxide dismutase-like (SOD-like) activity of a citrate-stabilized colloid solution of ultrasmall CeO2 nanoparticles (3 nm) in biochemical models. The trolox (a water-soluble analogue of vitamin E) equivalent antioxidant capacity of a 1 µmol/L CeO2 sol was 0.049 ± 0.004 µmol/L; thus, the ability of CeO2 to act as a free radical scavenger is about 20 times lower than that of trolox. The antioxidant activity was estimated by the mathematical modeling method. The free radical scavenging rate constants were 2000 nM–1 min–1 for trolox and k1 = 300 nM–1 min–1 and k2 = 4 nM–1 min–1 for cerium dioxide. The SOD-like activity of 1 mmol/L СеО2 in SOD activity units was 2.00 ± 0.03 nmol/L. Thus, the activity of CeO2 as a SOD mimetic is about six orders of magnitude lower than the activity of the native enzyme.

Aflatoxin compromises development of the preimplantation bovine embryo through mechanisms independent of reactive oxygen production

Aflatoxin is a potent carcinogen often found in animal feedstuffs. Although it reportedly impairs development of the preimplantation pig embryo, it is not known whether it adversely affects development of the preimplantation bovine embryo. We conducted 3 experiments to investigate this possibility and determine whether deleterious effects of aflatoxin were caused by increased production of reactive oxygen species (ROS). Experiments were conducted with embryos produced in vitro and cultured after fertilization with various concentrations of aflatoxin. For experiment 1, embryos were treated with 0 (control), 40, 400, or 4,000 µg/L of aflatoxin B1 (AFB1). Treatment at all concentrations of AFB1 tended to reduce cleavage rate, with the 2 highest concentrations having significant effects. As compared with the control, 40 µg/L AFB1 reduced the percentage of oocytes becoming blastocysts and the percentage of cleaved embryos becoming blastocysts (19.7 vs. 8.1% and 30.3 vs. 14.3%, respectively). Complete inhibition of blastocyst formation occurred at concentrations of 400 and 4,000 µg/L of AFB1. Experiments 2 and 3 involved a 2 × 2 factorial design with effects of AFB1 (0 and 40 µg/L), the antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water-soluble analog of vitamin E; 0 and 5 µM), and their interaction on production of ROS in putative zygotes (experiment 2) and development to the blastocyst stage (experiment 3). Production of ROS was increased by AFB1, and this effect was reversed by Trolox. However, Trolox did not prevent the reduction in development to the blastocyst stage caused by AFB1. Thus, the anti-developmental effects of AFB1 are not caused solely by increased ROS production. Rather, other underlying mechanisms exist for the adverse effects of aflatoxin on embryonic development. Overall, results indicate the potential for feeding aflatoxin-contaminated feed to cause embryonic loss in cattle.

Suppression of riboflavin-sensitized singlet oxygen generation by l-ascorbic acid, 3-O-ethyl-l-ascorbic acid and Trolox

Riboflavin (RF), a water-soluble vitamin B2, is an endogenous singlet oxygen photosensitizer in human skin and eye. Time profiles of the near-infrared phosphorescence of singlet oxygen generated by RF have been measured in the absence and presence of l-ascorbic acid (AA, vitamin C), 3-O-ethyl-l-ascorbic acid (3-EtAA) and Trolox (TX, a water-soluble analogue of vitamin E) in phosphate buffer (pH 6.8). These substances suppress the RF-photosensitized singlet oxygen generation. For example, the quantum yield of singlet oxygen generation is decreased to a third by adding 0.4 mmol dm-3 AA or TX (the concentration of dissolved oxygen in air-saturated water is 0.27 mmol dm-3). AA and TX are more efficient suppressors of RF-photosensitized singlet oxygen generation than 3-EtAA. The bimolecular rate constants for quenching of the excited singlet and triplet states of RF by AA, 3-EtAA and TX have been determined through measurements of fluorescence and transient absorption. These measurements suggest that the observed suppression is due to the quenching of the excited singlet and triplet states of RF by AA, 3-EtAA and TX. The bimolecular rate constants for quenching of singlet oxygen by AA, 3-EtAA and TX were determined to be 1.8 × 108, 0.27 × 108, and 4.4 × 108 mol-1 dm3 s-1, respectively.

A major component of vitamin E, α-tocopherol inhibits the anti-tumor activity of crizotinib against cells transformed by EML4-ALK

Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. α-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay. On the other hand, other members of the vitamin E family, namely, β-tocopherol, γ-tocopherol, δ-tocopherol, and α-tocotrienol, and a water-soluble analog of vitamin E, Trolox had no effects on the anti-tumor activity of crizotinib in cells transformed by EML4-ALK. Collectively, these results revealed the risk of the anti-tumor activity of crizotinib being attenuated when it is administrated in combination with vitamin E supplements containing α-tocopherol as a major component.

Design, synthesis and evaluation of novel dihydrostilbene derivatives as potential anti-melanogenic skin-protecting agents

The stems of Dendrobium orchids (Orchidaceae), also known as Shi Hu, have been used for medicinal purposes for centuries in oriental countries. In fact, the health benefits of Shi Hu have been evidenced by its modern pharmacological actions on conquering oxidative stress in pathological conditions. From the extracts of two commonly used Dendrobium species, we obtained discernible amounts of stilbenoids, explicitly trans-resveratrol (1) and dihydro-resveratrol (2), which are prototypical antioxidants. When applied to cultured melanocytes, these stilbenoids, dihydro-resveratrol (2) in particular, significantly reduced melanin formation via inhibiting tyrosinase activity and expression of tyrosinase-related proteins. By utilizing dihydro-resveratrol (2) as the basic structural unit, we synthesized 11 novel dihydrostilbene derivatives (3–13) in good yields and purity, with manipulative steps. In addition to their anti-melanogenic activity, some of the novel derivatives are indeed potential antioxidants as they quenched intracellular oxidative radicals in a manner more efficient than Trolox, a water-soluble analogue of vitamin E, and thus premeditated beneficial to skin protection.

Reactive Oxygen Species Produced by a Photodynamic Effect Induced Calcium Signal in Neurons and Astrocytes.

Photodynamic therapy (PDT) leads to production of reactive oxygen species (ROS) and cell destruction due to oxidative stress. We used photodynamic effect of photosensitizer radachlorin to unravel the effect of photo-induced oxidative stress on the calcium signal and lipid peroxidation in primary culture of cortical neurons and astrocytes using live cell imaging. We have found that irradiation in presence of 200nM of radachlorin induces calcium signal in primary neurons and astrocytes. Photo-induced neuronal calcium signal depends on internal calcium stores as it was still observed in calcium-free medium and could be blocked by depletion of endoplasmic reticulum (ER) stores with inhibitor of sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) thapsigargin. Both inhibitors of phospholipase C activity U73122 and water-soluble analogue of vitamin E Trolox suppressed calcium response activated by PDT. We have also observed that the photodynamic effect of radachlorin induces lipid peroxidation in neurons and astrocytes. This data demonstrate that lipid peroxidation induced by PDT in neurons and astrocytes leads to activation of phospholipase C that results in production of inositol 1,4,5-trisphosphate (IP3).

Local administration of Trolox, a vitamin E analog, reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury

SummaryBackgroundHand flexor tendon injuries are compromised with tendon adhesion. Tendon adhesion forms between flexor tendon and tendon sheath, reduces the range of motion of fingers, and affects their function. Oxidative stress is increased in flexor tendon after injury and might play a role in tendon adhesion formation. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water-soluble analog of vitamin E, is antioxidative. Trolox reduced oxidative stress and the expression of fibrotic cytokines in the bile gut ligation animal model. Vitamin C and Trolox are strong antioxidants, but they might also have prooxidant properties. The prooxidant properties of vitamin C and Trolox are different. In this study, our aim was to determine the effect of Trolox in reducing tendon adhesion formation.MethodsFlexor digitorum profundus tendon injury was induced in 54 Kai-Mei Chicken according to a well-established protocol. After wound closure, an injection of 50 μL saline, 10mM Trolox, or 100mM Trolox was administered into the wound area. At 2 weeks or 6 weeks after the surgery, chicken feet were harvested for gliding test, high-resolution ultrasound measurement on a fibrotic area, and histology.ResultsAt Week 2 after the surgery, Trolox has no effect on the flexion angle and gliding resistance, whereas a significant improvement was observed in the flexion angle and gliding resistance in the Trolox-treated groups at Week 6. However, no dose response was observed. In the ultrasound measurement, there was no significant difference in the fibrotic mass in the Trolox-treated group as compared to the saline group at Week 2. At Week 6, fibrotic mass was significantly reduced in both Trolox-treated groups. From the histological examination, the Trolox-treated groups presented a higher cellularity at Week 2 as compared to the saline group, and reduced fibrosis and adhesion at Week 6.ConclusionOur results suggest that local administration of Trolox can reduce tendon adhesion, and a higher dose of Trolox did not have negative effects.Clinical SignificanceTrolox solution might be feasible to reduce tendon adhesion via intraoperative injection at the wound area during tendon repair.

Application of new phenolic antioxidants for cryopreservation of sturgeon sperm

Heterocyclic derivatives of butylated hydroxytoluene (BHT) were studied as cryoprotectants of the basic media for cryopreservation of the Russian sturgeon sperm. Rates of lipid peroxidation of sturgeon sperm before and after cryopreservation were reduced in the presence of the studied compounds, exceeding the effects of BHT and water-soluble analogue of vitamin E, trolox. The most efficient antioxidant has the effective concentration of 0.1 mM. Novel antioxidant agents as cryomedium supplements not only reduced the level of lipid peroxidation, but also enhanced the translational motility of the sperm of the Russian sturgeon after defrosting.

Exposure to low-dose rotenone precipitates synaptic plasticity alterations in PINK1 heterozygous knockout mice

Heterozygous mutations in the PINK1 gene are considered a susceptibility factor to develop early-onset Parkinson's disease (PD), as supported by dopamine hypometabolism in asymptomatic mutation carriers and subtle alterations of dopamine-dependent striatal synaptic plasticity in heterozygous PINK1 knockout (PINK1+/−) mice. The aim of the present study was to investigate whether exposure to low-dose rotenone of heterozygous PINK1+/− mice, compared to their wild-type PINK1+/+ littermates, could impact on dopamine-dependent striatal synaptic plasticity, in the absence of apparent structural alterations.Mice were exposed to a range of concentrations of rotenone (0.01–1mg/kg). Chronic treatment with concentrations of rotenone up to 0.8mg/kg did not cause manifest neuronal loss or changes in ATP levels both in the striatum or substantia nigra of PINK1+/− and PINK1+/+ mice. Moreover, rotenone (up to 0.8mg/kg) treatment did not induce mislocalization of the mitochondrial membrane protein Tom20 and release of cytochrome c in PINK1+/− striata. Accordingly, basic electrophysiological properties of nigral dopaminergic and striatal medium spiny neurons (MSNs) were normal. Despite the lack of gross alterations in neuronal viability in chronically-treated PINK1+/−, a complete loss of both long-term depression (LTD) and long-term potentiation (LTP) was recorded in MSNs from PINK1+/− mice treated with a low rotenone (0.1mg/kg) concentration. Even lower concentrations (0.01mg/kg) blocked LTP induction in heterozygous PINK1+/− MSNs compared to PINK1+/+ mice. Of interest, chronic pretreatment with the antioxidants alpha-tocopherol and Trolox, a water-soluble analog of vitamin E and powerful antioxidant, rescued synaptic plasticity impairment, confirming that, at the doses we utilized, rotenone did not induce irreversible alterations.In this model, chronic exposure to low-doses of rotenone was not sufficient to alter mitochondrial integrity and ATP production, but profoundly impaired the expression of long-term plasticity at corticostriatal synapses in PINK1 heterozygous knockout mice, suggesting that disruption of synaptic plasticity may represent an early feature of a pre-manifesting state of the disease, and a potential tool to test novel neuroprotective agents.