L-cysteine Methyl Ester Research Articles

Construction and Performance Study of a Dual-Network Hydrogel Dressing Mimicking Skin Pore Drainage for Photothermal Exudate Removal and On-Demand Dissolution.

In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel-network PEG-CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four-arm polyethylene glycol/carboxymethyl chitosan (4-Arm-PEG-SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near-infrared light (NIR) irradiation, the PEG-CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland-like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG-CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full-thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L-cysteine methyl ester hydrochloride (L-CME) can provides the on-demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes.

Characterization of L-cysteine methyl ester hydrochloride–stabilized gold nanoparticles

Characterization of L-cysteine methyl ester hydrochloride–stabilized gold nanoparticles

Anti-Inflammatory Actions of Expectorants in a Rat Carrageenan-Induced Footpad Edema Model.

S-Carboxymethyl-L-cysteine (SCMS) exhibits sputum-regulating and anti-inflammatory actions. Previous studies reported the anti-inflammatory effects of SCMS on chronic inflammatory diseases, but no study has examined these effects on acute inflammatory diseases. In this study, we investigated the anti-inflammatory effects of SCMS in a rat carrageenan-induced footpad edema model, which is routinely used as an acute inflammation model. Expectorants were administered to rats with footpad edema induced by subcutaneously administering 1%λ-carrageenan to the footpad of the left posterior limb, and the dose dependency of the anti-inflammatory effects was evaluated. As a result, even when the dose of SCMS was increased to 400 mg/kg, there were no inhibitory effects on edema. Furthermore, we examined the inhibitory effects of other expectorants (ambroxol hydrochloride, N-acetyl-L-cysteine, L-cysteine ethylester hydrochloride, and L-cysteine methylester hydrochloride), which were reported to exhibit anti-inflammatory effects on chronic inflammation, on edema. However, none of these expectorants inhibited edema.

L-cysteine methyl ester overcomes the deleterious effects of morphine on ventilatory parameters and arterial blood-gas chemistry in unanesthetized rats.

We are developing a series of thiolesters that produce an immediate and sustained reversal of the deleterious effects of opioids, such as morphine and fentanyl, on ventilation without diminishing the antinociceptive effects of these opioids. We report here the effects of systemic injections of L-cysteine methyl ester (L-CYSme) on morphine-induced changes in ventilatory parameters, arterial-blood gas (ABG) chemistry (pH, pCO2, pO2, sO2), Alveolar-arterial (A-a) gradient (i.e., the index of alveolar gas-exchange within the lungs), and antinociception in unanesthetized Sprague Dawley rats. The administration of morphine (10 mg/kg, IV) produced a series of deleterious effects on ventilatory parameters, including sustained decreases in tidal volume, minute ventilation, inspiratory drive and peak inspiratory flow that were accompanied by a sustained increase in end inspiratory pause. A single injection of L-CYSme (500 μmol/kg, IV) produced a rapid and long-lasting reversal of the deleterious effects of morphine on ventilatory parameters, and a second injection of L-CYSme (500 μmol/kg, IV) elicited pronounced increases in ventilatory parameters, such as minute ventilation, to values well above pre-morphine levels. L-CYSme (250 or 500 μmol/kg, IV) also produced an immediate and sustained reversal of the deleterious effects of morphine (10 mg/kg, IV) on arterial blood pH, pCO2, pO2, sO2 and A-a gradient, whereas L-cysteine (500 μmol/kg, IV) itself was inactive. L-CYSme (500 μmol/kg, IV) did not appear to modulate the sedative effects of morphine as measured by righting reflex times, but did diminish the duration, however, not the magnitude of the antinociceptive actions of morphine (5 or 10 mg/kg, IV) as determined in tail-flick latency and hindpaw-withdrawal latency assays. These findings provide evidence that L-CYSme can powerfully overcome the deleterious effects of morphine on breathing and gas-exchange in Sprague Dawley rats while not affecting the sedative or early stage antinociceptive effects of the opioid. The mechanisms by which L-CYSme interferes with the OR-induced signaling pathways that mediate the deleterious effects of morphine on ventilatory performance, and by which L-CYSme diminishes the late stage antinociceptive action of morphine remain to be determined.

Simultaneous analysis of derivatized allyl isothiocyanate together with its phase II metabolites by ultra-high-performance liquid chromatography/tandem mass spectrometry.

Allyl isothiocyanate (AITC) in food products such as wasabi is commonly analyzed by gas chromatography/mass spectrometry (GC/MS), while liquid chromatography/mass spectrometry (LC/MS) is more suitable for the polar metabolites. The development of an effective method for the simultaneous determination of AITC and its phase II metabolites is needed to support drug metabolism and pharmacokinetics (DMPK) studies. Derivatization of AITC by reaction with N-(tert-butoxycarbonyl)-L-cysteine methyl ester (t BocCysME) was used for ultra-high-performance liquid chromatography/electrospray ionization mass spectrometry (UHPLC/ESI-MS) analysis, allowing the simultaneous determination with its phase II metabolites. At room temperature, reaction conditions have been optimized to maximize the reaction of AITC with t BocCysME quantitively. Reaction selectivity was examined by the presence of AITC metabolites. Quantification of AITC was performed by multiple reaction monitoring (MRM) with an external calibration method and applied on the serum of C57BL/6J mouse for a DMPK study. The limit of quantification (LOQ) was determined to be 0.842 nM from the derivatization method and by UHPLC/MS/MS analysis. The method accuracy in the mouse serum samples was 75 ± 2% with a relative standard deviation (RSD) of 3.0% of method variation. The UHPLC/MS/MS analysis gave RSDs of 0.2% and 1.8% for intra-day and inter-day variations. With the newly developed method, AITC could be detected in mouse serum upon oral administration for the first time. An analytical method involving a rapid derivatization pre-treatment and quantitative UHPLC/ESI-QqQ-MS/MS analysis has been developed for a biological sample assay of AITC, enabling selective and sensitive detection of the AITC derivative and AITC metabolites simultaneously. The method developed could be applied to the DMPK study of AITC as well.

Dimethylcysteine (DiCys)/o-Phthalaldehyde Derivatization for Chiral Metabolite Analyses: Cross-Comparison of Six Chiral Thiols.

Metabolomics profiling using liquid chromatography-mass spectrometry (LC-MS) has become an important tool in biomedical research. However, resolving enantiomers still represents a significant challenge in the metabolomics study of complex samples. Here, we introduced N,N-dimethyl-l-cysteine (dimethylcysteine, DiCys), a chiral thiol, for the o-phthalaldehyde (OPA) derivatization of enantiomeric amine metabolites. We took interest in DiCys because of its potential for multiplex isotope-tagged quantification. Here, we characterized the usefulness of DiCys in reversed-phase LC-MS analyses of chiral metabolites, compared against five commonly used chiral thiols: N-acetyl-l-cysteine (NAC); N-acetyl-d-penicillamine (NAP); isobutyryl-l-cysteine (IBLC); N-(tert-butoxycarbonyl)-l-cysteine methyl ester (NBC); and N-(tert-butylthiocarbamoyl)-l-cysteine ethyl ester (BTCC). DiCys and IBLC showed the best overall performance in terms of chiral separation, fluorescence intensity, and ionization efficiency. For chiral separation of amino acids, DiCys/OPA also outperformed Marfey’s reagents: 1-fluoro-2-4-dinitrophenyl-5-l-valine amide (FDVA) and 1-fluoro-2-4-dinitrophenyl-5-l-alanine amide (FDAA). As proof of principle, we compared DiCys and IBLC for detecting chiral metabolites in aqueous extracts of rice. By LC–MS analyses, both methods detected twenty proteinogenic l-amino acids and seven d-amino acids (Ala, Arg, Lys, Phe, Ser, Tyr, and Val), but DiCys showed better analyte separation. We conclude that DiCys/OPA is an excellent amine-derivatization method for enantiomeric metabolite detection in LC-MS analyses.

Paratrimerins J-Y, Dimeric Coumarins Isolated from the Stems of Paramignya trimera.

Paratrimerins J-Y (1-13 and 16-18), new dimeric coumarins, were obtained from the EtOH(aq) extract of the stems of Paramignya trimera (Rutaceae) utilizing LC/MS guided isolation. The structures of the dimeric coumarins were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of paratrimerins J-Y along with those of two known dimers paratrimerins A (14) and B (15) were established on the basis of the experimental and simulated ECD data. In addition, the absolute configurations of the sugar units of paratrimerins A, B, and J-V (1-15) were confirmed by LC/MS analysis on l-cysteine methyl ester and phenyl isothiocyanate derivatives. The variety of the absolute configurations of the dimeric diastereomers 1-15 highlighted a diversity in stereochemical outcomes following a Diels-Alder biosynthesis in P. trimera. With regard to P. trimera being a recently emerging medicinal resource for liver cancer, the dimers 1-18 were evaluated for cytotoxicity against a wide panel of human cancer cell lines. Paratrimerin W (16) was cytotoxic toward Huh7 hepatocellular carcinoma, HT1080 fibrosarcoma, and HT29 colorectal cancer cells with IC50 values of 14.9, 18.4, and 22.5 μM, respectively.

Modulation and Protection Effects of Antioxidant Compounds against Oxidant Induced Developmental Toxicity in Zebrafish.

The antioxidant effect of compounds is regularly evaluated by in vitro assays that do not have the capability to predict in vivo protective activity or to determine their underlying mechanisms of action. The aim of this study was to develop an experimental system to evaluate the in vivo protective effects of different antioxidant compounds, based on the zebrafish embryo test. Zebrafish embryos were exposed to tert-butyl hydroperoxide (tBOOH), tetrachlorohydroquinone (TCHQ) and lipopolysaccharides from Escherichia coli (LPS), chemicals that are known inducers of oxidative stress in zebrafish. The developmental toxic effects (lethality or dysmorphogenesis) induced by these chemicals were modulated with n-acetyl l-cysteine and Nω-nitro l-arginine methyl ester hydrochloride, dimethyl maleate and dl-buthionine sulfoximine in order to validate the oxidant mechanism of oxidative stress inducers. The oxidant effects of tBOOH, TCHQ, and LPS were confirmed by the determination of significant differences in the comparison between the concentration–response curves of the oxidative stress inducers and of the modulators of antioxidant status. This concept was also applied to the study of the effects of well-known antioxidants, such as vitamin E, quercetin, and lipoic acid. Our results confirm the zebrafish model as an in vivo useful tool to test the protective effects of antioxidant compounds.

Interaction of cysteine and its derivatives with monolayers of dipalmitoylphosphatidylcholine

Molecular interactions between l-cysteine (Cys) and its ester derivatives (Cysx); l-cysteine ethyl ester (CE), l-cysteine methyl ester (CM) and N-acetyl l-cysteine (NAC) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were investigated using Langmuir film balance technique. The effect of charge on monolayers made of cysteine and three ester derivatives with DPPC was investigated by working with un-buffered and buffered subphases. Also, the effects of cysteine derivatives interaction with DPPC monolayers were studied measuring the change in the surface tension upon aminoacid injection in the subphase whilst keeping lipid molecular density and lateral packing controlled.Cysteine and its ester derivatives showed interfacial activity reducing the air/water surface tension (πi) by 4 mN m−1. However, ester derivatives were able to insert into preformed DPPC monolayers at much higher surface pressures (Δπ), indicating a preferential interaction of Cysx with DPPC.The results indicate that, although the different derivatives of cysteine presented low surface activity, they were able to favourably interact with DPPC monolayers. Also, compression isotherms experiments in binary mixtures indicate that the more surface active compounds stabilized the gel phase of DPPC. The charge on cysteine and its derivatives did not increase the observed effects.

Fabrication Of Gold Nanoparticles In Absence Of Surfactant As In Vitro Carrier Of Plasmid DNA.

PurposeThis work aimed to synthesize surfactant-free AuNPs for targeted delivery of plasmid DNA encoded p53 gene and to avoid conventional production method of Gold nanoparticles (AuNPs) which may adversely affect the final shape, diversity, and size due to accumulation of the formulated surfactant – gold complex to the surface.MethodsThe AuNPs were fabricated using seeded-growth method with L-Cystine methyl ester hydrochloride as capping agent, then loaded with plasmid DNA encoded p53 gene. The resultant AuNPs and AuNPs-p53 complex were evaluated for physical characteristics and morphology. Confirmation of complex formation was performed using gel electrophoresis. Furthermore, the efficient delivery and cytotoxicity behavior of the encoded gene were examined on both healthy lung cells (WI38) and cancerous lung cells (A549).ResultsL-cysteine methyl ester hydrochloride AuNPs showed acceptable physical characteristics (30 nm, +36.9 mv, and spherical morphology). P53 attachment to AuNPs was confirmed by gel electrophoresis. The RT-PCR proved the overexpression of p53 by the fabricated AuNPs-p53 complex. The high percentage of cell viability in normal lung cell line (WI 38) proved the safety of L-cysteine methyl ester functionalized AuNPs. Additionally, the apoptotic effect due to expression of p53 gene loaded on AuNPs was only prominent in lung cancer cell line (A549), revealing selectivity and targeting efficiency of anticancer AuNPs-p53 complex.ConclusionAuNPs can be considered as a potential delivery system for effective transfection of plasmid DNA which can be used for successful treatment of cancer.

Multi-functional core-shell Fe3O4@Au nanoparticles for cancer diagnosis and therapy.

Multi-functional core-shell Fe3O4@Au nanoparticles (Fe3O4@Au-DOX-mPEG/PEG-FA NPs) conjugated with doxorubicin (DOX), methoxy poly(ethylene glycol) (mPEG), and folic acid-linked poly(ethylene glycol) (PEG-FA) were synthesized for cancer theranostic applications. In the developed NPs, the DOX was chemically conjugated at the surface of core-shell Fe3O4@Au NPs using L-cysteine methyl ester (LCME) as a linker by acid-sensitive hydrazone bond. The formation of Fe3O4@Au-DOX-mPEG/PEG-FA NPs was confirmed by 1H-NMR analysis. The TEM image and DLS studies showed that the mean diameter of the prepared NPs was about 18 and 38 nm, respectively. Due to the existence of superparamagnetic Fe3O4, the Fe3O4@Au-DOX-mPEG/PEG-FA NPs presented the saturation magnetization (Ms) value of 23 emu/g. The developed NPs displayed the maximum amount of drug release in the acidic medium than that in the mild alkaline medium because of the presence of acid-sensitive hydrazone bond. Due to the presence of FA, the Fe3O4@Au-DOX-mPEG/PEG-FA NPs displayed the increased cellular uptake through a folate-receptor-mediated endocytosis, which results in the improved cytotoxic effect on the HeLa cells. Under the laser irradiation, the cytotoxicity of Fe3O4@Au-DOX-mPEG/PEG-FA NPs was found to be improved due to the photothermal effect of Au shell existing in the NPs. These results reveal that the Fe3O4@Au-DOX-mPEG/PEG-FA NPs could be a promising tumour-targeted drug delivery system with the capabilities of combined MR/CT imaging, photothermal, and chemotherapy of tumours.

A Biocompatible Nanodendrimer for Efficient Adsorption and Reduction of Hg(II)

Mercury is a neurotoxic metal at very low concentrations and can lead to severe human health problems. In this work, we synthesized a novel heterogeneous dendrimer for the elimination and reduction of Hg(II) from H2O using SiO2–Al2O3 nanoparticles individually grafted with l-cysteine methyl ester (LCME), triazine, and diethylenetriamine. Applying Freundlich, Langmuir, and Sips isotherm equilibrium along with the pseudo-first-order (PFO), and pseudo-second-order (PSO) kinetic models, we studied how the nanobiodendrimer’s Hg(II) adsorption was affected by various parameters, like initial amount of Hg(II), adsorbent dosage, reaction time, solution temperature, interfering ions, and initial pH. Our results concluded that only 10 min of reaction time was needed to attain equilibrium (2639 mg g–1). The uptake kinetics also indicated the mechanism of adsorption is according to a PSO model, proving that the rate-confining stage of the Hg(II) ion uptake is chemical adsorption. Thermodynamic parameters (ΔG, ΔS, and...

Isolation and Structure Determination of a New Lumichrome Glycoside Isolated from a Soil Streptomyces sp. KCB16C001

Microbial studies of soil samples collected at Ochang, Korea led to the isolation of the actinobacterium Streptomyces sp. KCB16C001. Subsequent LC/MS analysis of the culture extract for dereplication purposes enabled the identification of a new metabolite ochangoside (1), whose chemical structure was determined to be 1-( α -L-rhamnosyl)-lumichrome by scale-up purification and structure elucidation procedures based mainly on NMR and MS spectroscopic data. Determination of the stereochemistry of the sugar moiety was achieved by LC/MS analysis of the sugar derivatized with L-cysteine methyl ester and o -tolyl isothiocyanate. Our results represent a rare example of natural lumichrome glycoside with a sugar unit attached at N −1.

Design, Synthesis, and Safener Activity of Novel Methyl (R)-N-Benzoyl/Dichloroacetyl-Thiazolidine-4-Carboxylates.

A series of novel methyl (R)-N-benzoyl/dichloroacetyl-thiazolidine-4-carboxylates were designed by active substructure combination. The title compounds were synthesized using a one-pot route from l-cysteine methyl ester hydrochloride, acyl chloride, and ketones. All compounds were characterized by IR, 1H NMR, 13C NMR, and HRMS. The structure of 4q was determined by X-ray crystallography. The biological tests showed that the title compounds protected maize from chlorimuron-ethyl injury to some extent. The ALS activity assay showed that the title compounds increased the ALS activity of maize inhibited by chlorimuron-ethyl. Molecular docking modeling demonstrated that Compound 4e competed against chlorimuron-ethyl to combine with the herbicide target enzyme active site, causing the herbicide to be ineffective.

Molecular view of the structural reorganization of water in DPPC multilamellar membranes induced by l-cysteine methyl ester

In order to study the interaction between l-cysteine methyl ester (CM) and multilamellar vesicles (MLV's) of DPPC, an extensive study was made by various techniques such as Infrared and Raman spectroscopy and Differential Scanning Calorimetry (DSC).Our results revealed by the different techniques used that CM interacts with the DPPC in the region of the polar head, specifying with the phosphate groups, replacing water molecules of hydration by modifying the hydration of the polar head.By Infrared spectroscopy and DSC we observed an increase in the main transition temperature (Tm) and a gradual loss of the pre-transition (Tp) with the increase of the molar ratio CM:DPPC.Of the analyzed, we can conclude that the interaction of CM with DPPC alters the degree of hydration of the membrane altering properties of the same as the transition temperature.Moreover, the results of the thiol site behavior in CM interacting in the CM/DPPC complex will be reveal the possibility of unknown functional roles of the lipidic components of the membrane.

Sensitizing effects of an organovanadium compound during adjuvant therapy with cyclophosphamide in a murine tumor model

Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium. In addition, recent studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively towards malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium compound, oxovanadium(IV)-l-cysteine methyl ester complex (VC-IV). In this study, VC-IV (1mg/kg b.w., p.o.) was administered alone as well as in combination with cyclophosphamide (25mg/kg b.w., i.p.) in concomitant and pretreatment schedules. The results showed that VC-IV in combination with cyclophosphamide resulted in an improved therapeutic efficacy as evidenced by reduction of tumor growth and prolongation of life span. The observed potentiation was mediated through generation of ROS in tumor cells, which ultimately led to significant DNA damage, and apoptosis in tumor cells. Further studies revealed that VC-IV sensitized tumor cells to cyclophosphamide therapy by down-regulating the anti-apoptotic protein Bcl-2 and by up-regulating molecules like p53, Bax, cytochrome c, caspases, which led to PARP cleavage and apoptosis. Significant inhibition of angiogenesis along with reduction in the levels of VEGF-A and MMP-9 in the tumor bed by VC-IV further contributed to the sensitization accomplished by VC-IV. Moreover, VC-IV ameliorated cyclophosphamide-induced hematopoietic, hepatic and genetic damages by modulating the antioxidant status in normal organs. Thus, the present study clearly demonstrated the sensitizing and protective efficacy of VC-IV and indicates it may serve as a promising adjuvant in cancer chemotherapy.

Adsorption of mercury ions from wastewater by a hyperbranched and multi-functionalized dendrimer modified mixed-oxides nanoparticles

In this paper, a novel heterogeneous nanodendrimer with generation of G2.0 was prepared by individual grafting of diethylenetriamine, triazine and l-cysteine methyl ester on the modified aluminum–silicate mixed oxides as a potent adsorbent of Hg(II) ions from aqueous media. The prepared nanodendrimer was characterized by nuclear magnetic resonance spectrum (1H NMR and 13C NMR), Fourier transform infrared spectroscopy (FT-IR), Diffuse reflectance UV–Vis spectroscopy (DR UV–Vis), zeta potential (ζ), inductively coupled plasma atomic emission spectroscopy (ICP-AES), transmission electron microscopy (TEM), scanning electron microscopy (SEM), nitrogen adsorption experiments at −196°C and elemental analysis. Equilibrium and kinetic models for Hg(II) ions removal were used by investigating the effect of the contact time, adsorbent dosage, initial Hg(II) ions concentrations, effect of solution’s temperature, interfering ions, and initial pH. The contact time to approach equilibrium for higher removal was 6min (3232mgg−1). The removal of Hg(II) ions has been assessed in terms of pseudo-first- and -second-order kinetics, and the Freundlich, Langmuir and Sips isotherms models have also been applied to the equilibrium removal data. The removal kinetics followed the mechanism of the pseudo-second order equation, where the chemical sorption is the rate-limiting step of removal process and not involving mass transfer in solution, which was further proved by several techniques such as zeta potential, FT-IR and DS UV–vis. The thermodynamic parameters (ΔG, ΔH and ΔS) implied that the removal of mercury ions was feasible, spontaneous and chemically exothermic in nature between 15 and 80°C. The nanodendrimer indicated high reusability due to its high removal ability after 15 adsorption–desorption runs. The adsorption mechanisms of Hg(II) ions onto the nanodendrimer was further studied by diverse techniques such as FTIR, EDS, zeta potential, DR UV–Vis spectroscopy and SEM. The possible mechanism of the Hg(II) ions adsorption onto the nanodendrimer could be carried out through the various paths such as electrostatic interaction, complexation, toxic metal chelation and ionic exchange, which eventually resulted in the hydrolysis and precipitation of the adsorbed Hg(II). The l-cysteine methyl ester nanodendrimer could also remove the mercury ions from the Persian Gulf water even after five times of recycling.

Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems.

The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS). L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed. 734±58μmol L-Cysteine methyl ester and 562±71μmol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270nm. Blank SEDDS possessed a zeta potential value between -5.7 and -8.6mV, whereas thiomers-SEDDS between -14.6 and -17.2mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45min. During cell viability studies no severe toxic effects were detected. The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.

Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin

ABSTRACTObjective: The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice.Methods: CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule.Results: CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice.Discussion: In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy.

An oxovanadium(IV) complex protects murine bone marrow cells against cisplatin-induced myelotoxicity and DNA damage

Cisplatin (CDDP) is one of the first-line anticancer drugs that has gained widespread use against various forms of human malignancies. But, the therapeutic outcome of CDDP therapy is limited due to its adverse effects including myelotoxicity and DNA damage which may lead to the subsequent risk of developing secondary cancer. Hence, in search of a suitable cytoprotectant, this study investigated the probable protective efficacy of an oxovanadium(IV) complex, namely oxovanadium(IV)-L-cysteine methyl ester complex (VC-IV) against CDDP-induced myelosuppression and genotoxic damage in the bone marrow cells of Swiss albino mice. CDDP was administered intraperitoneally (5 mg/kg b.w.) and VC-IV was administered orally (1 mg/kg b.w.) in concomitant and 7 d pretreatment schedule. Treatment with VC-IV in CDDP-treated mice significantly (p < 0.01) enhanced bone marrow cell proliferation and inhibited cell death in the bone marrow niche indicating improvement of CDDP-induced myelotoxicity. The organovanadium compound also significantly (p < 0.01) reduced the percentage of chromosomal aberrations, the frequency of micronuclei formation, and the extent of DNA damage. The observed chemoprotective effect of VC-IV was attributed to its anti-oxidant efficacy which significantly (p < 0.01) attenuated CDDP-induced generation of free radicals, and restored (p < 0.01) the levels of oxidized and reduced glutathione. Hence, VC-IV may serve as a promising candidate for future development to decrease the deleterious effects of CDDP in the bone marrow cells of cancer patients and associated secondary complications.