ABSTRACT
Iron Chlorin e6 (ICE6), a star plant growth regulator (PGR) with independent intellectual property rights in China, has demonstrated its efficacy through numerous field experiments. We innovatively employed salting-out assisted liquid-liquid extraction (SALLE) with HPLC-UV/Vis to detect ICE6 residues in water, soil, garlic seeds, and sprouts. Using methanol and a C18 column with acetonitrile: 0.1% phosphoric acid mobile phase (55:45, v:v), we achieved a low LOQ of 0.43 to 0.77 µg kg-1. Calibration curves showed strong linearity (R2 > 0.992) within 0.01 to 5.00 mg kg-1. Inter-day and intra-day recoveries (0.05 to 0.50 mg kg-1) demonstrated high sensitivity and accuracy (recoveries: 75.36% to 107.86%; RSD: 1.03% to 8.78%). Additionally, density functional theory (DFT) analysis aligned UV/Vis spectra and indicated ICE6's first-order degradation (2.03 to 4.94 days) under various environmental conditions, mainly driven by abiotic degradation. This study enhances understanding of ICE6's environmental behavior, aids in risk assessment, and guides responsible use in agroecosystems.
Subject(s)
Garlic , Metalloporphyrins , Chromatography, High Pressure Liquid/methods , Hydrolysis , Soil , Liquid-Liquid Extraction/methodsABSTRACT
Licarin A, a dihydrobenzofuranic neolignan presents in several medicinal plants and seeds of nutmeg, exhibits strong activity against protozoans responsible for Chagas disease and leishmaniasis. From biomimetic reactions by metalloporphyrin and Jacobsen catalysts, seven products were determined: four isomeric products yielded by epoxidation from licarin A, besides a new product yielded by a vicinal diol, a benzylic aldehyde, and an unsaturated aldehyde in the structure of the licarin A. The incubation with rat and human liver microsomes partially reproduced the biomimetic reactions by the production of the same epoxidized product of m/z 343 [M + H]+. In vivo acute toxicity assays of licarin A suggested liver toxicity based on biomarker enzymatic changes. However, microscopic analysis of tissues sections did not show any tissue damage as indicative of toxicity after 14 days of exposure. New metabolic pathways of the licarin A were identified after in vitro biomimetic oxidation reaction and in vitro metabolism by rat or human liver microsomes.
Subject(s)
Lignans , Metalloporphyrins , Rats , Humans , Animals , Biomimetics , Oxidation-Reduction , Lignans/toxicity , Metalloporphyrins/metabolism , Microsomes, Liver/metabolismABSTRACT
A simple and sensitive colorimetric assay for detecting organophosphorus pesticides (OPs) was developed based on 3,3',5,5'-tetramethylbenzidine (TMB)/hydrogen peroxide (H2O2)/dodecyl trimethylammonium bromide (DTAB)-tetramethyl zinc (4-pyridinyl) porphyrin (ZnTPyP). In this system, based on the peroxidase-like activity of DTAB-ZnTPyP, H2O2 decomposes to produce hydroxyl radicals, which oxidize TMB, resulting in blue oxidation products. The OPs (trichlorfon, dichlorvos, and thimet) were first combined with DTAB-ZnTPyP through electrostatic interactions. The OPs caused a decrease in the peroxidase-like activity of DTAB-ZnTPyP due to spatial site blocking. At the same time, π-interactions occurred between them, and these interactions also inhibited the oxidation of TMB (652 nm), thus making the detection of OPs possible. The limits of detection for trichlorfon, dichlorvos, and thimet were 0.25, 1.02, and 0.66 µg/L, respectively, and the corresponding linear ranges were 1-35, 5-45, and 1-40 µg/L, respectively. Moreover, the assay was successfully used to determine OPs in cabbage, apple, soil, and traditional Chinese medicine samples (the recovery ratios were 91.8-109.8%), showing a great promising potential for detecting OPs also in other complex samples.
Subject(s)
Pesticides , Porphyrins , Bromides , Colorimetry/methods , Dichlorvos , Hydrogen Peroxide , Metalloporphyrins , Organophosphorus Compounds , Peroxidases , Pesticides/analysis , Trichlorfon , Zinc , Zinc CompoundsABSTRACT
OBJECTIVE: Pedicled perforator partial or complete necrosis with a rate of 13.7%. This study was undertaken to test whether preconditioning with transcutaneous electrical nerve stimulation (TENS) monitored by infrared thermography protect against partial necrosis by converting the choke anastomoses to the true anastomoses via inducing heme oxygenase-1 (HO-1) in a rat pedicled perforator flap model. METHODS: Seventy-two Sprague-Dawley rats were randomly assigned to the control, the TENS, the TENS + SnPP (tin protoporphyrin; HO-1 activity inhibitor; 50 µmol/kg) and the TENS +0.9% saline groups. On the unilateral dorsum of the rats, a rectangular flap donor site of 11 × 3 cm was marked out, which contained three perforator angiosomes and two choke zones. On days 1, 3 and 4, 1 hour of TENS (biphasic pulses, 25 mA, 80 Hz, 200 µs) was applied to the flap donor sites, respectively. On day 5, after the flap donor sites were assessed by infrared thermography, the flaps were harvested based on the deep circumflex iliac artery perforator. RESULTS: Infrared thermography showed that the choke zones in the flap donor sites presented white in the TENS and the TENS +0.9% saline groups, whereas they presented red in the control and the TENS + SnPP groups. Postmortem arteriography showed that the number of arterioles across each choke zone significantly increased in the TENS and the TENS +0.9% saline groups compared with the control and the TENS + SnPP groups. Immunohistochemistry and western blot showed a significant increase in HO-1 in the choke zones after TENS preconditioning. The necrotic area percentage of the flaps was significantly decreased in the TENS (4.3% ± 2.6%) and the TENS +0.9% saline groups (4.5% ± 2.3%) compared with the control (24.8% ± 5.0%) ( P < 0.001); there was no significant difference between the TENS and the TENS + SnPP (24.4% ± 7.3%) groups. CONCLUSIONS: These data show that TENS preconditioning monitored by infrared thermography might be a promising strategy to prevent pedicled perforator flaps from partial necrosis.
Subject(s)
Perforator Flap , Transcutaneous Electric Nerve Stimulation , Animals , Graft Survival , Heme Oxygenase-1/pharmacology , Metalloporphyrins , Necrosis , Perforator Flap/blood supply , Protoporphyrins/pharmacology , Rats , Rats, Sprague-Dawley , Saline Solution , Thermography , Tin/pharmacologyABSTRACT
This study constructed a novel biomimetic enzyme electrochemical biosensor based on tetraphenyl metalloporphyrins functionalized multi-walled carbon nanotubes (MWCNTs). The effect of central metal ions on the catalytic activity of tetraphenyl metalloporphyrin biomimetic enzyme was investigated. It was found that the change of central metal ions had a significant effect on the catalytic performance of metalloporphyrin and Zinc(II) tetraphenylporphyrin (ZnTPP) had the most excellent catalytic property. The electrochemical behaviors of tert-butylhydroquinone (TBHQ) on ZnTPP/MWCNTs modified electrode were investigated. It was found that the redox peak current was increased significantly, which was attributed to the redox peak current to the electrocatalytic activity of ZnTPP and the synergistic effect between ZnTPP and MWCNTs. A strong linear relationship was shown in the concentration range of 0.01 to 1000 µM. This electrochemical sensor also had excellent repeatability, storage, and interference resistance. This work provided a simple and sensitive method for the determination of TBHQ.
Subject(s)
Metalloporphyrins , Nanotubes, Carbon , Antioxidants , Biomimetics , Electrochemical Techniques , Electrodes , Hydroquinones , Nanotubes, Carbon/chemistry , Oxidoreductases , Plant OilsABSTRACT
Mimicking the coordination geometry of the active metal sites of natural enzymes is an efficient strategy in designing therapeutic chemicals with enzymelike in vivo reaction thermodynamics and kinetics. In this study, this chemical concept has been applied for the in situ synthesis of natural antioxidase mimics for catalytic anti-inflammatory treatment by using rheumatoid arthritis, a common and hardly curable immune-mediated diseases, as an example. Briefly, a composite nanomedicine has been first constructed by loading cationic porphyrin ligands into a manganese-engineered mesoporous silica nanocarrier, which can respond to a mildly acidic environment to concurrently release manganous ions and porphyrin ligands, enabling their subsequent coordination and synthesis of manganese porphyrin with a coordination environment of an active Mn site similar to those of the metal sites in natural superoxide dismutase (SOD) and catalase. Due to the strong metal-ligand exchange coupling enabled by the N-ethylpyridinium-2-yl groups tetrasubstituted in the meso positions of N4-macroheterocycles, such a manganese porphyrin presents the SOD-like activity of disproportionating superoxide anions via outer-sphere proton-coupled one-electron transfer (diaquamanganese(III)/monoaquamanganese(II) cycling), as well as the catalase-like activity of disproportionating hydrogen peroxide via inner-sphere proton-coupled two-electron transfer (diaquamanganese(III)/dioxomanganese(V) cycling). Cellular experiments demonstrated the high antioxidative efficacy of the composite nanomedicine in M1 macrophages by promoting their polarization shift to the anti-inflammatory M2 phenotype. Equally importantly, the silicon-containing oligomers released from the manganese silicate nanocarrier can act as heterogeneous nucleation centers of hydroxyapatite for facilitating biomineralization by bone mesenchymal stem cells. Finally, an in vivo adjuvant-induced arthritis animal model further reveals the high efficacy of the nanomedicine in treating rheumatoid arthritis.
Subject(s)
MetalloporphyrinsABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of tin mesoporphyrin (SnMP) in neonates with hyperbilirubinemia (HB) due to hemolysis. STUDY DESIGN: This multicenter, placebo-controlled phase 2b study (NCT01887327) randomized newborns (35-42 weeks) with hemolysis started on phototherapy (PT) to placebo (Ctrl), SnMP 3.0 mg/kg, or SnMP 4.5 mg/kg given once IM within 30 min of initiation of PT. RESULTS: In all, 91 patients were randomized (Ctrl: n = 30; 3 mg/kg SnMP: n = 30; 4.5 mg/kg SnMP: n = 31). At 48 h TSB significantly increased in Ctrl by 17.5% (95% CI 5.6-30.7; p = 0.004) and significantly decreased by -13% (95% CI -21.7 to -3.2; p = 0.013) in the 3.0 mg/kg and by -10.5% (95% CI -19.4 to -0.6; p = 0.041) in the 4.5 mg/kg group. Decreases in SnMP groups were significant (p < 0.0001) vs Ctrl. CONCLUSION: SnMP with PT significantly reduced TSB by 48 h. SnMP may be useful as a treatment for HB in neonates with hemolysis.
Subject(s)
Erythroblastosis, Fetal , Hyperbilirubinemia, Neonatal , Erythroblastosis, Fetal/therapy , Female , Heme Oxygenase (Decyclizing) , Hemolysis , Humans , Hyperbilirubinemia/therapy , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Metalloporphyrins , PhototherapyABSTRACT
Enzymes that bear a nonnative or artificially introduced metal center can engender novel reactivity and enable new spectroscopic and structural studies. In the case of metal-organic cofactors, such as metalloporphyrins, no general methods exist to build and incorporate new-to-nature cofactor analogs in vivo. We report here that a common laboratory strain, Escherichia coli BL21(DE3), biosynthesizes cobalt protoporphyrin IX (CoPPIX) under iron-limited, cobalt-rich growth conditions. In supplemented minimal media containing CoCl2, the metabolically produced CoPPIX is directly incorporated into multiple hemoproteins in place of native heme b (FePPIX). Five cobalt-substituted proteins were successfully expressed with this new-to-nature cobalt porphyrin cofactor: myoglobin H64V V68A, dye decolorizing peroxidase, aldoxime dehydratase, cytochrome P450 119, and catalase. We show conclusively that these proteins incorporate CoPPIX, with the CoPPIX making up at least 95% of the total porphyrin content. In cases in which the native metal ligand is a sulfur or nitrogen, spectroscopic parameters are consistent with retention of native metal ligands. This method is an improvement on previous approaches with respect to both yield and ease-of-implementation. Significantly, this method overcomes a long-standing challenge to incorporate nonnatural cofactors through de novo biosynthesis. By utilizing a ubiquitous laboratory strain, this process will facilitate spectroscopic studies and the development of enzymes for CoPPIX-mediated biocatalysis.
Subject(s)
Metalloporphyrins/chemistry , Porphyrins/biosynthesis , Porphyrins/chemistry , Biocatalysis , Cobalt/chemistry , Cobalt/metabolism , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Heme/metabolism , Iron , Metals/chemistry , Myoglobin/chemistry , Protoporphyrins/biosynthesis , Protoporphyrins/chemistryABSTRACT
Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2'-n-butoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5,6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1,4, 7,10] tetraazacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 µM, while Mn(II) chloro N-(phenolato)-N,N'-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 µM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.
Subject(s)
Catalase/metabolism , Manganese/metabolism , Organometallic Compounds/metabolism , Superoxide Dismutase/metabolism , Animals , Antioxidants/metabolism , Cell Line , Glutathione Peroxidase/metabolism , Humans , Hydrogen Peroxide/metabolism , Metalloporphyrins/metabolism , Molecular Mimicry , Oxidation-Reduction , Oxidative Stress , Porphyrins/metabolism , Reactive Oxygen Species/metabolism , Superoxides/metabolismABSTRACT
Herein, the microscopic and spectroscopic characterization of a novel non-covalent electron donor-acceptor system, in which three different metalloporphyrins (1, 2, and 3) play the dual role of light harvester and electron donor with SWCNTs as electron acceptor, is described. To this end, microscopy, that is, atomic force microscopy (AFM) and transmission electron microscopy (TEM) corroborate the formation of 1-SWCNT, 2-SWCNT, and 3-SWCNT. Spectroscopy by means of Raman, fluorescence, and transient absorption spectroscopy confirmed efficient charge-transfer interaction from photoexcited metalloporphyrins to SWCNTs in the ground and excited state of 1-SWCNT, 2-SWCNT, and 3-SWCNT. The complementary use of spectroelectrochemical and transient absorption measurements substantiates the formation of one-electron oxidized metalloporphyrins after photoexcitation. Multiwavelength global analysis provides insights into the charge-separation and recombination processes in 1-SWCNT, 2-SWCNT, and 3-SWCNT upon photoexcitation. Notably, both the charge-separation and recombination dynamics are fastest in 2-SWCNT. Importantly, the strongest interactions in the steady-state experiments are associated with the fastest excited state decay in the time-resolved measurements.
Subject(s)
Metalloporphyrins , Nanotubes, Carbon , Microscopy, Atomic Force , Spectrum AnalysisABSTRACT
Caffeine naturally occurs in tea and cocoa, which is also used as an additive in beverages and has pharmacological effects such as refreshing, antidepressant, and digestion promotion, but excessive caffeine can cause harm to the human body. In this work, based on the specific response between nano zinc 5, 10, 15, 20-tetra(4-pyridyl)-21H-23H-porphine (nano ZnTPyP)-CdTe quantum dots (QDs) and caffeine, combined with chemometrics, a visual paper-based sensor was constructed for rapid and on-site detection of caffeine. The fluorescence of QDs can be quenched by nano ZnTPyP. When caffeine is added to the system, it can pull nano ZnTPyP off the surface of the QDs to achieve fluorescence recovery through electrostatic attraction and nitrogen/zinc coordination. The detection range is 5 × 10-11~3 × 10-9 mol L-1, and the detection limit is 1.53 × 10-11 mol L-1 (R2 = 0.9990) (S/N = 3). The paper-based sensor constructed exhibits good results in real samples, such as tea water, cell culture fluid, newborn bovine serum, and human plasma. Therefore, the sensor is expected to be applied to the rapid instrument-free detection of caffeine in food and biological samples.Graphical abstract.
Subject(s)
Cadmium Compounds/chemistry , Caffeine/blood , Colorimetry/methods , Metalloporphyrins/chemistry , Paper , Quantum Dots/chemistry , Tellurium/chemistry , Zinc Compounds/chemistry , Animals , Cattle , Colorimetry/instrumentation , Humans , Limit of Detection , Tea/chemistry , Water/analysisABSTRACT
BACKGROUND: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications. MATERIALS AND METHODS: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed "all-in-one" FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent. RESULTS: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3-5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs. CONCLUSION: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.
Subject(s)
Hafnium/chemistry , Hyperthermia, Induced , Metal-Organic Frameworks/chemistry , Metalloporphyrins/chemistry , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Phototherapy , Animals , Contrast Media/chemistry , Fluorescence , Folic Acid/therapeutic use , HeLa Cells , Humans , Magnetic Resonance Imaging , Mice, Inbred BALB C , Nanoparticles/ultrastructure , Neoplasms/radiotherapy , Photoacoustic Techniques , Radiotherapy, Image-GuidedABSTRACT
In vitro manipulation of spermatozoa leads to deleterious changes of structure and function that occur mainly due to oxidative stress, therefore, prevention or treatment is a strategy to improve the functions of processed sperm. In the present study, the aim was to evaluate the effects of MnTBAP supplementation, a compound with antioxidant activity, on in vitro capacitation conditions of thawed equine sperm. For this purpose, stallion spermatozoa (2 × 106 cells/mL) were incubated in the sperm-TLP base medium for 4 h in which there were three different conditions: non-capacitating, capacitating, and capacitating plus 150 mM MnTBAP. There were incubations for 4 h at 37.5 °C in a humidified air atmosphere. Sample analysis was performed immediately after thawing (0 h), and at the end of the incubation period (4 h), unless otherwise indicated. The following variables were evaluated for spermatozoa: plasma membrane integrity and fluidity, acrosome integrity, intracellular calcium concentrations, intracellular pH, tyrosine phosphorylation, ATP concentrations, motility and heterologous zona-binding assay, using flow cytometry, fluorescent microscopy and/or chemiluminescence, depending on the most appropriate procedure for the variable being evaluated. Results indicated that capacitation-like changes were synergistically induced by the cAMP agonists, phosphodiesterase inhibitor and bicarbonate. The presence of bovine serum albumin was harmful to the plasma membrane. The MnTBAP supplementation had a positive effect on viability-related markers (plasma membrane integrity, membrane fluidity, associated with greater intracellular pH) when there were capacitating conditions. In conclusion, the activity of MnTBAP contributes to improving the in vitro incubation conditions of frozen-thawed stallion sperm.
Subject(s)
Cryopreservation/veterinary , Horses/physiology , Metalloporphyrins/pharmacology , Semen Preservation/veterinary , Sperm Capacitation/drug effects , Animals , MaleABSTRACT
Sperm cryopreservation is widely used in assisted reproduction and male infertility therapy; however, it induces oxidative stress affecting sperm quality. This work evaluated the effect of the antioxidant MnTBAP during vitrification steps in human spermatozoa. First, the effect of MnTBAP on viability and ROS production was evaluated. Then, the spermatozoa were vitrified in straws with the vitrification, warming and post-warming incubation media separately supplemented with MnTBAP. An untreated control was included. The sperm viability, ROS production, total and progressive motility were evaluated. The results showed that the direct exposure of spermatozoa to MnTBAP significantly decreases the ROS levels in comparison with the untreated control without affecting the viability. The supplementation of the vitrification medium with MnTBAP did not affect the parameters analysed. However, the supplementation of the warming and incubation post-warming media resulted in a decrease in ROS production and maintained viability and motility for 4 hr after warming with concentrations up to 100 µM of MnTBAP. Higher concentrations of MnTBAP caused a decrease in total motility. In conclusion, the use of MnTBAP during the warming or post-warming incubation media has beneficial effect decreasing ROS levels and maintaining the viability and motility during the vitrification procedure.
Subject(s)
Semen Preservation , Vitrification , Cryopreservation , Humans , Male , Metalloporphyrins , Sperm Motility , Spermatozoa , Superoxide DismutaseABSTRACT
BACKGROUND AND OBJECTIVES: Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic "stress test" for gauging gene responsiveness and antioxidant reserves. DESIGN: , setting, participants, & measurementsA total of 18 healthy volunteers and 24 participants with stage 3 CKD (n=12; eGFR 30-59 ml/min per 1.73 m2) or stage 4 CKD (n=12; eGFR 15-29 ml/min per 1.73 m2) were injected once with SnPP (9, 27, or 90 mg). Plasma and/or urinary antioxidant proteins were measured at baseline and for up to 4 days post-SnPP dosing. Kidney safety was gauged by serial measurements of BUN, creatinine, eGFR, albuminuria, and four urinary AKI biomarkers (kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, cystatin C, and N-acetyl glucosaminidase). RESULTS: Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (r=-0.85 to -0.95). All four proteins manifested statistically significant dose- and time-dependent elevations after SnPP injection. However, marked intersubject differences were observed. p21 responses to high-dose SnPP and HO-1 responses to low-dose SnPP were significantly suppressed in participants with CKD versus healthy volunteers. SnPP was well tolerated by all participants, and no evidence of nephrotoxicity was observed. CONCLUSIONS: SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.
Subject(s)
Kidney Function Tests , Metalloporphyrins/administration & dosage , Oxidative Stress , Protoporphyrins/administration & dosage , Renal Insufficiency, Chronic/diagnosis , Adult , Aged , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p21/blood , Cyclin-Dependent Kinase Inhibitor p21/urine , Female , Ferritins/blood , Ferritins/urine , Glomerular Filtration Rate , Heme Oxygenase-1/blood , Heme Oxygenase-1/urine , Humans , Infusions, Intravenous , Male , Middle Aged , NAD(P)H Dehydrogenase (Quinone)/blood , NAD(P)H Dehydrogenase (Quinone)/urine , Predictive Value of Tests , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/urineABSTRACT
Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085-0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.
Subject(s)
Iodine Radioisotopes/adverse effects , Metalloporphyrins/therapeutic use , Radiation-Protective Agents/therapeutic use , Radiopharmaceuticals/adverse effects , Thyroid Neoplasms/radiotherapy , Animals , Cell Line, Tumor , Female , Humans , Metalloporphyrins/pharmacology , Mice, Inbred C57BL , Radiation-Protective Agents/pharmacology , Salivary Glands/drug effects , Salivary Glands/pathology , Salivary Glands/radiation effects , Thyroid Gland/drug effects , Thyroid Gland/pathology , Thyroid Gland/radiation effects , Thyroid Neoplasms/pathologyABSTRACT
Fluorescent dyes, as a key factor in fluorescence imaging, usually exhibit a low signal-to-noise ratio (SNR) due to the limited loading capacities of delivery systems (usually less than 10.0 wt%) and their uncontrolled release. Herein, we developed a type of pH-responsive nanoplatform (MnO2/ZnCOF@Au&BSA) based on a zinc porphyrin covalent organic framework (COF), in which the zinc porphyrin (ZnPor) loading rate is 22.5 wt%. At pH = 7.4, the interlinked ZnPor in the assembly state did not show a fluorescence signal ("off" state). Together with the pH-triggered disintegration of ZnCOF in tumor cells (pH = 5.5), the scattered ZnPor displayed an obvious fluorescence signal recovery ("on" state). Simultaneously, the shed BSA-coated gold nanoparticles ingeniously caused the fluorescence signal to be further amplified through the metal-enhanced fluorescence effect, which was about 3.0-fold higher in vivo than in the free ZnPor group. Combined with the excellent photothermal therapy effect by the nanoplatform itself with the tumor inhibition rate of 79.5%, this nanosystem effectively solves the problem of low loading capacities and imaging SNR by traditional delivery systems, and successfully develops the potential of COFs for fluorescence imaging, achieving the purpose of integration of diagnosis and treatment.
Subject(s)
Drug Delivery Systems , Gold , Hyperthermia, Induced , Manganese Compounds , Metalloporphyrins , Nanostructures/chemistry , Neoplasms, Experimental/therapy , Oxides , Photochemotherapy , Animals , Female , Gold/chemistry , Gold/pharmacology , Hep G2 Cells , Humans , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Metalloporphyrins/chemistry , Metalloporphyrins/pharmacology , Mice , Oxides/chemistry , Oxides/pharmacologyABSTRACT
Acetylcholinesterase (AChE) biosensor technology is widely applied in the detection of organophosphate pesticides in agricultural production via the inhibition of AChE activity by organophosphates. However, the AChE electrode has some drawbacks, such as low stability and high overpotential. Combining the advantages of multiwalled carbon nanotubes (MWCNTs) and ionic liquids, we constructed a novel bienzyme electrode [Cl/iron porphyrin (FePP)-modified MWCNTs/AChE/glassy carbon electrode], which included AChE and mimetic oxidase FePP. In this electrode, FePP is covalently bound to the AChE carrier via ionic liquid for increased electrode sensitivity and stability. Under optimal conditions, this novel biosensor has a monocrotophos detection limit of 3.2 × 10-11 mol/L and good recovery of 89-104%. After 5 weeks of storage at 4 °C, the oxidation current was 97.8% of its original value. The biosensor has high stability and sensitivity for monocrotophos detection and is a promising device for monitoring food safety. Graphical abstract The complete synthesis process of Cl/FePP-MWCNTs/AChE/GCE.
Subject(s)
Acetylcholinesterase/chemistry , Biosensing Techniques/methods , Enzymes, Immobilized/chemistry , Metalloporphyrins/chemistry , Monocrotophos/analysis , Nanotubes, Carbon/chemistry , Pesticides/analysis , Biomimetic Materials/chemistry , Brassica/chemistry , Ionic Liquids/chemistry , Iron Compounds/chemistry , Lactuca/chemistry , Limit of Detection , Nanotubes, Carbon/ultrastructure , Onions/chemistryABSTRACT
The development of plant viral nanoparticles (VNP) loaded with different molecular versions of a photodynamic drug is described. Specifically, tobacco mosaic virus (TMV) and tobacco mild green mosaic virus (TMGMV) are developed as drug carriers that encapsulate the monocationic, dicationic, tricationic, and tetracationic versions of a porphyrin-based photosensitizer drug (Zn-Por). While TMV has been extensively explored for various nanotechnology applications, this is the first study investigating TMGMV for medical applications. Light-activated cancer cell killing of Zn-Por-loaded VNPs is studied in vitro using melanoma and cervical cancer models. Native and nucleolin-targeted VNP drug carriers are developed and their efficacy assessed. A fivefold increase in cancer cell killing is observed using nucleolin-targeted TMV loaded with tricationic Zn-Por and displaying the nucleolin-specific F3 peptide.
Subject(s)
Melanoma, Experimental/drug therapy , Metalloporphyrins , Nanoparticles , Photochemotherapy , Tobacco Mosaic Virus/chemistry , Animals , Cell Line, Tumor , Drug Carriers/chemistry , Drug Carriers/pharmacology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Metalloporphyrins/chemistry , Metalloporphyrins/pharmacology , Mice , Nanoparticles/chemistry , Nanoparticles/therapeutic useABSTRACT
The extract of Sappan Lignum, the heartwood of Caesalpinia sappan L., has been used in medicine to improve blood circulation. Recently, the application of microwave extraction methods has been a major focus of research into the extraction of components from natural sources. In this experiment, we compared the antiinflammatory effects of Sappan Lignum prepared by heat70% EtOH extraction (CSEH70E) and microwave70% EtOH extraction (CSEMW70E). Highperformance liquid chromatography analysis was used to identify the compounds in these extracts. The heat70% EtOH and microwave70% EtOH extracts of Sappan Lignum had different chromatograms. CSEMW70E significantly inhibited the protein expression of iNOS and COX2, PGE2, TNFα, and reduced NO and IL1ß production in macrophages exposed to LPS, whereas, only high concentrations of CSEH70E (20 µg/ml) resulted in any effects. Furthermore, CSEMW70E upregulated heme oxygenase1 (HO1) expression. In addition, the use of tin protoporphyrin, an inhibitor of HO1, confirmed the inhibitory effects of CSEMW70E on proinflammatory mediators. These results suggested that the CSEMW70Emediated upregulation of HO1 played an important role in the antiinflammatory effects of macrophages. Therefore, these findings showed that microwave extraction can be utilized to improve the extraction efficiency and biological activity of Sappan Lignum.