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1.
Pestic Biochem Physiol ; 200: 105809, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38582581

RESUMEN

Culex quinquefasciatus is the main vector of lymphatic filariasis in Brazil, which present resistance to commercial insecticides. Nowadays, essential oils (EOs) exhibiting larvicidal activity, such as those derived from Piper alatipetiolatum, provide a promising alternative for vector control, including Culex species. This study aimed to investigate the larvicidal activity and the oxidative stress indicators of the EO from P. alatipetiolatum in Cx. quinquefasciatus larvae. The EO was extracted from P. alatipetiolatum leaves using the hydrodistillation method, resulting in a yield of 7.2 ± 0.1%, analysed by gas chromatography coupled with spectrometry and gas chromatography coupled with flame ionization detector (GC-MS and GC-FID), and evaluated against Cx. quinquefasciatus larvae. Reactive Oxygen and Nitrogen Species (RONS), Catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and Thiol levels were used as oxidative stress indicators. Analysis by CG-MS and CG-FID revealed that the main compound in the EO was the oxygenated sesquiterpene ishwarone, constituting 78.6% of the composition. Furthermore, the EO exhibited larvicidal activity, ranging from 26 to 100%, with an LC50 of 4.53 µg/mL and LC90 of 15.37 µg/mL. This activity was accompanied by a significant increase in RONS production, alterations in CAT, GST, AChE activity, and thiol levels compared to the control groups (p < 0.05). To the best of our knowledge, this is the first report describing the larvicidal activity and oxidative stress induced by the EO from P. alatipetiolatum against Cx. quinquefasciatus larvae. Therefore, we propose that this EO shows promise as larvicidal agent for the effective control of Cx. quinquefasciatus larvae.


Asunto(s)
Aedes , Culex , Culicidae , Insecticidas , Aceites Volátiles , Piper , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Larva , Acetilcolinesterasa , Mosquitos Vectores , Insecticidas/farmacología , Insecticidas/química , Compuestos de Sulfhidrilo/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta
2.
J Mater Chem B ; 12(16): 3970-3983, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38563351

RESUMEN

Lipoic acid (LA), which has good safety and oral absorption, is obtained from various plant-based food sources and needs to be supplemented through human diet. Moreover, substances with a disulfide structure can enter cells through dynamic covalent disulfide exchange with thiol groups on the cell membrane surface. Based on these factors, we constructed LA-modified nanoparticles (LA NPs). Our results showed that LA NPs can be internalized into intestinal epithelial cells through surface thiols, followed by intracellular transcytosis via the endoplasmic reticulum-Golgi pathway. Further mechanistic studies indicated that disulfide bonds within the structure of LA play a critical role in this transport process. In a type I diabetes rat model, the oral administration of insulin-loaded LA NPs exhibited a more potent hypoglycemic effect, with a pharmacokinetic bioavailability of 5.42 ± 0.53%, representing a 1.6 fold enhancement compared to unmodified PEG NPs. Furthermore, a significant upregulation of surface thiols in inflammatory macrophages was reported. Thus, we turned our direction to investigate the uptake behavior of inflammatory macrophages with increased surface thiols towards LA NPs. Inflammatory macrophages showed a 2.6 fold increased uptake of LA NPs compared to non-inflammatory macrophages. Surprisingly, we also discovered that the antioxidant resveratrol facilitates the uptake of LA NPs in a concentration-dependent manner. This is mainly attributed to an increase in glutathione, which is involved in thiol uptake. Consequently, we employed LA NPs loaded with resveratrol for the treatment of colitis and observed a significant alleviation of colitis symptoms. These results suggest that leveraging the variations of thiol expression levels on cell surfaces under both healthy and diseased states through an oral drug delivery system mediated by the small-molecule nutrient LA can be employed for the treatment of diabetes and certain inflammatory diseases.


Asunto(s)
Compuestos de Sulfhidrilo , Ácido Tióctico , Ácido Tióctico/química , Animales , Compuestos de Sulfhidrilo/química , Administración Oral , Ratas , Humanos , Nanopartículas/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/administración & dosificación , Sistemas de Liberación de Medicamentos , Masculino , Inflamación/tratamiento farmacológico , Ratones , Propiedades de Superficie , Portadores de Fármacos/química , Insulina/metabolismo , Ratas Sprague-Dawley , Tamaño de la Partícula , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Células RAW 264.7
3.
Eur J Oncol Nurs ; 69: 102536, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452425

RESUMEN

PURPOSE: Antineoplastic drugs (ADs) are widely used in cancer treatment. Nurses in chemotherapy centers are exposed to these drugs during preparation. They can affect healthy cells, leading to teratogenic and mutagenic effects, as well as oxidative stress. This study aimed to evaluate oxidative stress biomarkers in the nurses exposed to these drugs. METHOD: This study was conducted on 30 nurses exposed to ADs and 30 nurses with no exposure to these drugs as non-exposed group. Oxidative stress biomarkers were measured in the blood serum samples of both groups, including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and blood thiol groups. RESULTS: Considering the possibility of confounding effect of nutritional supplement consumption, the effect of this factor was adjusted in the analysis. A significant difference was observed for CAT, SOD, thiol, and TAC biomarkers between two groups (P < 0.05). However, the difference in MDA and GPx biomarkers between two groups was not statistically significant. CONCLUSIONS: The findings of the present study showed that supplement consumption has a significant effect on the biomarker of total antioxidant capacity. Thus, total antioxidant capacity measurement is advised as the best biomarker for tracking oxidative status in nurses exposed to ADs due to its capacity to measure all antioxidants in the body, except the thiol group, and its lower cost when compared to other biomarkers. Furthermore, it can be claimed that the consumption of nutritional supplements has a greater effect on the non-enzymatic biomarkers of oxidative stress than on enzymatic antioxidant system.


Asunto(s)
Antineoplásicos , Antioxidantes , Humanos , Antioxidantes/análisis , Antioxidantes/metabolismo , Antioxidantes/farmacología , Estudios Transversales , Estrés Oxidativo , Biomarcadores , Superóxido Dismutasa/farmacología , Glutatión Peroxidasa/farmacología , Antineoplásicos/efectos adversos , Compuestos de Sulfhidrilo/farmacología
4.
Environ Sci Pollut Res Int ; 31(11): 16375-16387, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38315336

RESUMEN

Intensive sulphur fertilisation has been reported to improve the nutrient balance and growth of Cd-exposed plants, but the reasons of this phenomenon and the role of sulphur compounds in the resistance to cadmium are unclear. We investigated sulphur supplementation-induced changes in the surface properties of roots and the level of thiol peptides (PCs) in Cd-stressed Triticum aestivum L. (monocots clade) and Lactuca sativa L. (dicots clade) grown in nutrient solution. The combination of three sulphur (2 mM S-basic level, 6 or 9 mM S-elevated levels) and four cadmium (0, 0.0002, 0.02 or 0.04 mM Cd) concentrations was used. The physicochemical parameters of the roots were determined based on the apparent surface area (Sr), total variable surface charge (Q), cation exchange capacity (CEC) and surface charge density (SCD). In Cd-exposed plants supplied with sulphur, a different character and trend in the physicochemical changes (adsorption and ion exchange) of roots were noted. At the increased sulphur levels, as a rule, the Sr, CEC, Q and SCD values clearly increased in the lettuce but decreased in the wheat in the entire range of the Cd concentrations, except the enhanced Sr of wheat supplied with 6 mM S together with elevated (0.0002 mM) and unchanged (0.02, 0.04 mM Cd) value of this parameter at 9 mM S. This indicates a clade-specific and/or species-specific plant reaction. The 6 mM S appears to be more effective than 9 mM S in alleviation of the cadmium's toxic effects on roots. It was found that at 0.02 and 0.04 mM Cd, the use of 6 mM S limits the Cd accumulation in the roots of both species in comparison with the basic S fertilisation. Moreover, PC accumulation was much more efficient in wheat than in lettuce, and intensive sulphur nutrition generally induced biosynthesis of these chelating compounds. Physicochemical parameters together with quantitative and qualitative assessment of thiol peptides can be important indicators of the efficiency of root system functioning under cadmium stress. The differences between the species and the multidirectional character of the changes are a result of the involvement of a number of multi-level mechanisms engaged in the defence against metal toxicity.


Asunto(s)
Fitoquelatinas , Contaminantes del Suelo , Cadmio/toxicidad , Lactuca , Triticum , Azufre/farmacología , Compuestos de Sulfhidrilo , Suplementos Dietéticos , Raíces de Plantas , Contaminantes del Suelo/farmacología
5.
Phytother Res ; 38(3): 1555-1573, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38281735

RESUMEN

Anti-inflammatory and immune suppressive agents are required to moderate hyper-activation of lymphocytes under disease conditions or organ transplantation. However, selective disruption of mitochondrial redox has not been evaluated as a therapeutic strategy for suppression of T-cell-mediated pathologies. Using mitochondrial targeted curcumin (MitoC), we studied the effect of mitochondrial redox modulation on T-cell responses by flow cytometry, transmission electron microscopy, transcriptomics, and proteomics, and the role of Nrf2 was studied using Nrf2- /- mice. MitoC decreased mitochondrial TrxR activity, enhanced mitochondrial ROS (mROS) production, depleted mitochondrial glutathione, and suppressed activation-induced increase in mitochondrial biomass. This led to suppression of T-cell responses and metabolic reprogramming towards Treg differentiation. MitoC induced nuclear translocation and DNA binding of Nrf2, leading to upregulation of Nrf2-dependent genes and proteins. MitoC-mediated changes in mitochondrial redox and modulation of T-cell responses are abolished in Nrf2- /- mice. Restoration of mitochondrial thiols abrogated inhibition of T-cell responses. MitoC suppressed alloantigen-induced lymphoblast formation, inflammatory cytokines, morbidity, and mortality in acute graft-versus-host disease mice. Disruption of mitochondrial thiols but not mROS increase inculcates an Nrf2-dependent immune-suppressive disposition in T cells for the propitious treatment of graft-versus-host disease.


Asunto(s)
Curcumina , Curcumina/análogos & derivados , Enfermedad Injerto contra Huésped , Animales , Ratones , Curcumina/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Linfocitos T , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/patología , Compuestos de Sulfhidrilo/metabolismo , Compuestos de Sulfhidrilo/farmacología
6.
BMC Microbiol ; 24(1): 44, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297214

RESUMEN

L-arginine deiminase (ADI, EC 3.5.3.6) hydrolyzes arginine to ammonia and citrulline which is a natural supplement in health care. ADI was purified from Penicillium chrysogenum using 85% ammonium sulfate, DEAE-cellulose and Sephadex G200. ADI was purified 17.2-fold and 4.6% yield with a specific activity of 50 Umg- 1 protein. The molecular weight was 49 kDa. ADI expressed maximum activity at 40oC and an optimum pH of 6.0. ADI thermostability was investigated and the values of both t0.5 and D were determined. Kd increased by temperature and the Z value was 38oC. ATP, ADP and AMP activated ADI up to 0.6 mM. Cysteine and dithiothreitol activated ADI up to 60 µmol whereas the activation by thioglycolate and reduced glutathione (GSH) prolonged to 80 µmol. EDTA, α,α-dipyridyl, and o-phenanthroline inactivated ADI indicating that ADI is a metalloenzyme. N-ethylmaleimide (NEM), N-bromosuccinimide (NBS), butanedione (BD), dansyl chloride (DC), diethylpyrocarbonate (DEPC) and N-acetyl-imidazole (NAI) inhibited ADI activity indicating the necessity of sulfhydryl, tryptophanyl, arginyl, lysyl, histidyl and tyrosyl groups, respectively for ADI catalysis. The obtained results show that ADI from P. chrysogenum could be a potential candidate for industrial and biotechnological applications.


Asunto(s)
Penicillium chrysogenum , Hidrolasas/química , Hidrolasas/farmacología , Compuestos de Sulfhidrilo , Cisteína , Arginina
7.
Yakugaku Zasshi ; 144(1): 41-45, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38171793

RESUMEN

Methylmercury is a ubiquitous neurotoxic substance present in the environment, and health concerns, especially through the consumption of seafood, remain. Glutathione (GSH)-mediated detoxification and the excretion of methylmercury are known metabolic detoxification pathways. We have also discovered a mechanism by which endogenous super-sulfides convert methylmercury to nontoxic metabolites such as bis-methylmercury sulfide. However, these metabolites are present in very small quantities, and the significance of the detoxification of methylmercury by super-sulfides is not well understood. Methylmercury binds to thiol groups in vivo but can also react with highly reactive selenols (selenocysteine residues). Such covalent bonds (S-mercuration and Se-mercuration) are broken by nucleophilic substitution reactions with other thiol and selenols, however, the contribution of super-sulfides to this substitution reaction is not well understood. Interestingly, a recent study suggested that selenoprotein P, the major selenium transport protein in plasma, binds to methylmercury, however, Se-mercuration was not determined. In this review, we introduce these series of reactions and discuss their involvement with super-sulfides in methylmercury toxicity.


Asunto(s)
Compuestos de Metilmercurio , Selenio , Compuestos de Metilmercurio/metabolismo , Selenio/metabolismo , Glutatión/metabolismo , Compuestos de Sulfhidrilo , Sulfuros
8.
Redox Biol ; 69: 102969, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38064764

RESUMEN

Chemoproteomic profiling of sulfhydryl-containing proteins has consistently been an attractive research hotspot. However, there remains a dearth of probes that are specifically designed for sulfhydryl-containing proteins, possessing sufficient reactivity, specificity, distinctive isotopic signature, as well as efficient labeling and evaluation capabilities for proteins implicated in the regulation of redox homeostasis. Here, the specific selenium-containing probes (Se-probes) in this work displayed high specificity and reactivity toward cysteine thiols on small molecules, peptides and purified proteins and showed very good competitive effect of proteins labeling in gel-ABPP. We identified more than 6000 candidate proteins. In TOP-ABPP, we investigated the peptide labeled by Se-probes, which revealed a distinct isotopic envelope pattern of selenium in both the primary and secondary mass spectra. This unique pattern can provide compelling evidence for identifying redox regulatory proteins and other target peptides. Furthermore, our examiation of post-translational modification (PTMs) of the cysteine site residues showed that oxidation PTMs was predominantly observed. We anticipate that Se-probes will enable broader and deeper proteome-wide profiling of sulfhydryl-containing proteins, provide an ideal tool for focusing on proteins that regulate redox homeostasis and advance the development of innovative selenium-based pharmaceuticals.


Asunto(s)
Cisteína , Selenio , Cisteína/metabolismo , Compuestos de Sulfhidrilo/química , Péptidos/metabolismo , Proteoma/metabolismo , Oxidación-Reducción , Preparaciones Farmacéuticas
9.
Talanta ; 270: 125497, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38142611

RESUMEN

In this work we present the preparation of a 2D molybdenum disulphide nanosheets (2D-MoS2) and tetrahedral DNA nanostructures (TDNs) bioconjugate, and its application to the development of a bioassay for rapid and easy virus detection. The bioconjugate has been prepared by using TDNs carrying the capture probe labelled with 6-carboxyfluoresceine (6-FAM). As case of study to assess the utility of the assay developed, we have chosen the SARS-CoV-2 virus. Hence, as probe we have used a DNA sequence complementary to a region of the SARS-CoV-2 ORF1ab gene (TDN-ORF-FAM). This 6-FAM labelled capture probe is located on the top vertex of the tetrahedral DNA nanostructure, the three left vertices of TDNs have a thiol group. These TDNs are bounded to 2D-MoS2 surface through the three thiol groups, allowing the capture probe to be oriented to favour the biorecognition reaction with the analyte. This biorecognition resulting platform has finally been challenged to the detection of the SARS-CoV-2 ORF1ab gene sequence as the target model by measuring fluorescence before and after the hybridization event with a detection limit of 19.7fM. Furthermore, due to high sensitivity of the proposed methodology, it has been applied to directly detect the virus in nasopharyngeal samples of infected patients without the need of any amplification step. The developed bioassay has a wide range of applicability since it can be applied to the detection of any pathogen by changing the probe corresponding to the target sequence. Thus, a novel, hands-on strategy for rapid pathogen detection has proposed and has a high potential application value in the early diagnosis of infections causes by virus or bacteria.


Asunto(s)
Técnicas Biosensibles , Nanoestructuras , Humanos , Molibdeno , ADN/química , Hibridación de Ácido Nucleico , Nanoestructuras/química , Compuestos de Sulfhidrilo , Técnicas Biosensibles/métodos
10.
Eur Rev Med Pharmacol Sci ; 27(18): 8523-8530, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37782168

RESUMEN

OBJECTIVE: We aimed to investigate the relationship between intraoperative body temperature and thiol/disulfide balance in geriatric patients scheduled for elective transurethral prostate resection surgery with spinal anesthesia. PATIENTS AND METHODS: 71 patients classified as categories 1 and 2, according to American Society of Anesthesiologists (ASA) classification, were included in the study. The core temperature of the patients was recorded in the operating room after monitoring, at 5 and 30 minutes after spinal anesthesia. Total thiols, native thiols, disulfide amounts, disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were calculated as percentages after monitorization (Tpreoperative) and at 60 minutes after spinal anesthesia (Tintraoperative). RESULTS: The disulfide levels in the Tintraoperative period (29±8.9 mmol/L) were higher than the disulfide levels measured in the Tpreoperative period (18.2±8.8 mmol/L) (p<0.001). In the Tpreoperative period, the disulfide/native thiol (%) level was 4.6±2, while the disulfide/total thiol (%) level was 4.2±1.6. In the Tintraoperative period, the disulfide/native thiol (%) level was 8±2.3, while the disulfide/total thiol (%) level was 6.8±1.7. Native thiol/total thiol (%) levels for the Tpreoperative and Tintraoperative periods were 91.5±3.3 mmol/L and 86.3±3.4 mmol/L, respectively. A correlation was found between native, total thiol levels and patient age in the Tpreoperative and Tintraoperative periods. CONCLUSIONS: Oxidative stress can be reduced in geriatric patients with the possibility of developing involuntary perioperative hypothermia by regularly monitoring body temperature and applying warming techniques.


Asunto(s)
Anestesia Raquidea , Resección Transuretral de la Próstata , Masculino , Humanos , Anciano , Temperatura Corporal , Disulfuros , Compuestos de Sulfhidrilo , Estrés Oxidativo , Biomarcadores
11.
Plant Physiol Biochem ; 204: 108127, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37890229

RESUMEN

Enzymes of the sulfur assimilation pathway of plants have been identified as potential targets for herbicide development, given their crucial role in synthesizing amino acids, coenzymes, and various sulfated compounds. In this pathway, O-acetylserine (thiol) lyase (OAS-TL; EC 2.5.1.47) catalyzes the synthesis of L-cysteine through the incorporation of sulfate into O-acetylserine (OAS). This study used an in silico approach to select seven inhibitors for OAS-TL. The in silico experiments revealed that S-benzyl-L-cysteine (SBC) had a better docking score (-7.0 kcal mol-1) than the substrate OAS (-6.6 kcal mol-1), indicating its suitable interaction with the active site of the enzyme. In vitro experiments showed that SBC is a non-competitive inhibitor of OAS-TL from Arabidopsis thaliana expressed heterologously in Escherichia coli, with a Kic of 4.29 mM and a Kiu of 5.12 mM. When added to the nutrient solution, SBC inhibited the growth of maize and morning glory weed plants due to the reduction of L-cysteine synthesis. Remarkably, morning glory was more sensitive than maize. As proof of its mechanism of action, L-cysteine supplementation to the nutrient solution mitigated the inhibitory effect of SBC on the growth of morning glory. Taken together, our data suggest that reduced L-cysteine synthesis is the primary cause of growth inhibition in maize and morning glory plants exposed to SBC. Furthermore, our findings indicate that inhibiting OAS-TL could potentially be a novel approach for herbicidal action.


Asunto(s)
Arabidopsis , Herbicidas , Liasas , Arabidopsis/metabolismo , Cisteína , Cisteína Sintasa/metabolismo , Herbicidas/farmacología , Plantas/metabolismo , Compuestos de Sulfhidrilo/metabolismo
12.
Toxicon ; 235: 107316, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37827264

RESUMEN

Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m3, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC50 were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC50 were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant.


Asunto(s)
Lesión Pulmonar Aguda , Crocus , Neumonía , Edema Pulmonar , Ratas , Animales , Paraquat/toxicidad , Paraquat/uso terapéutico , Crocus/metabolismo , Interleucina-10 , Pioglitazona/toxicidad , Pioglitazona/uso terapéutico , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/patología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/patología , Pulmón , Edema Pulmonar/tratamiento farmacológico , Estrés Oxidativo , Lesión Pulmonar Aguda/inducido químicamente , Dexametasona/uso terapéutico , Superóxido Dismutasa/metabolismo , Compuestos de Sulfhidrilo/toxicidad , Compuestos de Sulfhidrilo/uso terapéutico
13.
J Nat Prod ; 86(7): 1654-1666, 2023 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-37458412

RESUMEN

Artemisia annua is the plant that produces artemisinin, an endoperoxide-containing sesquiterpenoid used for the treatment of malaria. A. annua extracts, which contain other bioactive compounds, have been used to treat other diseases, including cancer and COVID-19, the disease caused by the virus SARS-CoV-2. In this study, a methyl ester derivative of arteannuin B was isolated when A. annua leaves were extracted with a 1:1 mixture of methanol and dichloromethane. This methyl ester was thought to be formed from the reaction between arteannuin B and the extracting solvent, which was supported by the fact that arteannuin B underwent 1,2-addition when it was dissolved in deuteromethanol. In contrast, in the presence of N-acetylcysteine methyl ester, a 1,4-addition (thiol-Michael reaction) occurred. Arteannuin B hindered the activity of the SARS CoV-2 main protease (nonstructural protein 5, NSP5), a cysteine protease, through time-dependent inhibition. The active site cysteine residue of NSP5 (cysteine-145) formed a covalent bond with arteannuin B as determined by mass spectrometry. In order to determine whether cysteine adduction by arteannuin B can inhibit the development of cancer cells, similar experiments were performed with caspase-8, the cysteine protease enzyme overexpressed in glioblastoma. Time-dependent inhibition and cysteine adduction assays suggested arteannuin B inhibits caspase-8 and adducts to the active site cysteine residue (cysteine-360), respectively. Overall, these results enhance our understanding of how A. annua possesses antiviral and cytotoxic activities.


Asunto(s)
Artemisininas , COVID-19 , Proteasas de Cisteína , Humanos , Caspasa 8/metabolismo , Proteasas de Cisteína/metabolismo , Compuestos de Sulfhidrilo/farmacología , Cisteína/farmacología , SARS-CoV-2 , Extractos Vegetales/química , Artemisininas/química
14.
J Biochem Mol Toxicol ; 37(6): e23332, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37294177

RESUMEN

Constant, systematic exposure to rotenone has been utilized in animal models to induce Parkinsonism. Ellagic acid is a polyphenol with anti-inflammatory and antioxidative properties which is found in numerous natural fruits. Here, we investigated the therapeutic effects of ellagic acid in rotenone-induced toxicity in Drosophila melanogaster evaluating their antioxidant and mitoprotective properties. Adult flies were treated with rotenone and ellagic acid through their diet for 7 days, thereafter markers of neurotoxicity (acetylcholinesterase, monoamine oxidase, tyrosine hydroxylase), antioxidant and oxidative stress markers (hydrogen peroxide, nitric oxide, lipid peroxidation, protein carbonyl contents, catalase, total thiol, and nonprotein thiol) was measured. Mitochondrial respiration was also evaluated in the flies. Survival assay was carried out with both genders of the flies, and we observed a significant increase in the survival rate of flies exposed to both rotenone and ellagic acid when compared with the increased mortality rate in the groups exposed to rotenone alone. The impaired locomotion, altered redox status, and enzymes of neurotoxicity induced by rotenone were significantly ameliorated by ellagic acid to levels comparable to the control. In addition, rotenone-induced complex 1 inhibition and altered bioenergetic state were restored upon ellagic acid supplementation. These findings show the beneficial properties of ellagic acid against pesticides induced toxicity.


Asunto(s)
Antioxidantes , Rotenona , Animales , Femenino , Masculino , Antioxidantes/farmacología , Antioxidantes/metabolismo , Rotenona/toxicidad , Drosophila melanogaster/metabolismo , Ácido Elágico/farmacología , Acetilcolinesterasa/metabolismo , Estrés Oxidativo , Mitocondrias/metabolismo , Compuestos de Sulfhidrilo/metabolismo
15.
Sci Rep ; 13(1): 9294, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37286735

RESUMEN

The report presents the first method for simultaneous determination of plasma 2-(3-hydroxy-5-phosphonooxymethyl-2-methyl-4-pyridyl)-1,3-thiazolidine-4-carboxylic acid (HPPTCA), an adduct of cysteine (Cys) and active form of vitamin B6 pyridoxal 5'-phosphate (PLP), as well as total low molecular-weight thiols content, including Cys, homocysteine (Hcy), cysteinyl-glycine (Cys-Gly), and glutathione (GSH). The assay is based on high performance liquid chromatography coupled with ultraviolet detection (HPLC-UV) and involves disulfides reduction with tris(2-carboxyethyl)phosphine (TCEP), derivatization with 2-chloro-1-methylquinolinium tetrafluoroborate (CMQT) followed by sample deproteinization with perchloric acid (PCA). The chromatographic separation of obtained stable UV-absorbing derivatives is achieved on ZORBAX SB-C18 (150 × 4.6 mm, 5.0 µm) column using gradient elution with eluent consisted of 0.1 mol/L trichloroacetic acid (TCA), pH 1.7 and acetonitrile (ACN), delivered at a flow rate 1 mL/min. Under these conditions, the analytes are separated within 14 min at room temperature, and quantified by monitoring at 355 nm. Regarding HPPTCA, the assay linearity was demonstrated within a 1-100 µmol/L in plasma and the lowest concentration on the calibration curve was recognized as the limit of quantification (LOQ). The accuracy ranged from 92.74 to 105.57% and 95.43 to 115.73%, while precision varied from 2.48 to 6.99% and 0.84 to 6.98% for intra- and inter-day measurements, respectively. The utility of the assay was proved by application to plasma samples delivered by apparently healthy donors (n = 18) in which the HPPTCA concentration ranged from 19.2 to 65.6 µmol/L. The HPLC-UV assay provides complementary tool for routine clinical analysis, facilitating further studies on the role of aminothiols and HPPTCA in living systems.


Asunto(s)
Cisteína , Compuestos de Sulfhidrilo , Cromatografía Líquida de Alta Presión/métodos , Cisteína/análisis , Tiazolidinas , Glutatión/análisis , Fosfato de Piridoxal , Reproducibilidad de los Resultados
16.
Animal Model Exp Med ; 6(3): 221-229, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37272426

RESUMEN

BACKGROUND: Zataria multiflora and carvacrol showed various pharmacological properties including anti-inflammatory and anti-oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)-induced aortic and cardiac injury. METHODS: Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS) (1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro-ethanolic extract (ZME, 50-200 mg/kg, oral)- and carvacrol (25-100 mg/kg, oral)-treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. RESULTS: Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS-injected rats. CONCLUSIONS: The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.


Asunto(s)
Óxido Nítrico , Sepsis , Ratas , Masculino , Animales , Óxido Nítrico/farmacología , Lipopolisacáridos/toxicidad , Cardiotoxicidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas Wistar , Estrés Oxidativo/fisiología , Antioxidantes/farmacología , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Compuestos de Sulfhidrilo/farmacología
17.
Ultrason Sonochem ; 97: 106442, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37244085

RESUMEN

In this study, the effects of ultrasound treatment on the texture, physicochemical properties and protein structure of composite gels prepared by salted egg white (SEW) and cooked soybean protein isolate (CSPI) at different ratios were investigated. With the increased SEW addition, the ζ-potential absolute values, soluble protein content, surface hydrophobicity and swelling ratio of composite gels showed overall declining trends (P < 0.05), while the free sulfhydryl (SH) contents and hardness of exhibited overall increasing trends (P < 0.05). Microstructural results revealed that composite gels exhibited denser structure with the increased SEW addition. After ultrasound treatment, the particle size of composite protein solutions significantly decreased (P < 0.05), and the free SH contents of ultrasound-treated composite gels were lower than that of untreated composite gels. Moreover, ultrasound treatment enhanced the hardness of composite gels, and promoted the conversion of free water into non-flowable water. However, when ultrasonic power exceeded 150 W, the hardness of composite gels could not be further enhanced. FTIR results indicated that ultrasound treatment facilitated the composite protein aggregates to form a more stable gel structure. The improvement of ultrasound treatment on the properties of composite gels was mainly by promoting the dissociation of protein aggregates, and the dissociated protein particles further interacted to form denser aggregates through disulfide bond, thus facilitating the crosslinking and reaggregation of protein aggregates to form denser gel structure. Overall, ultrasound treatment is an effective approach to improve the properties of SEW-CSPI composite gels, which can improve the potential utilization of SEW and SPI in food processing.


Asunto(s)
Clara de Huevo , Proteínas de Soja , Proteínas de Soja/química , Agregado de Proteínas , Culinaria , Geles/química , Cloruro de Sodio , Agua/química , Compuestos de Sulfhidrilo
18.
Allergol Immunopathol (Madr) ; 51(3): 153-162, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37169573

RESUMEN

BACKGROUND: Previous studies have shown that Allium cepa (A. cepa) has relaxant and anti-inflammatory effects. In this research, A. cepa extract was examined for its prophylactic effect on lung inflammation and oxidative stress in sensitized rats. METHODS: Total and differential white blood cell (WBC) count in the blood, serum levels of oxidant and antioxidant biomarkers, total protein (TP) in bronchoalveolar lavage fluid (BALF), and lung pathology were investigated in control group (C), sensitized group (S), and sensitized groups treated with A. cepa and dexamethasone. RESULTS: Total and most differential WBC count, TP, NO2, NO3, MDA (malondialdehyde), and lung pathological scores were increased while lymphocytes, superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in sensitized animals compared to controls (p < 0.01 to p < 0.001). Treatment with all concentrations of extract significantly improved total WBC, TP, NO2, NO3, interstitial fibrosis, and emphysema compared to the S group (p < 0.05 to p < 0.001). Two higher concentrations of the extract significantly decreased neutrophil and monocyte count, malondialdehyde, bleeding and epithelial damage but increased lymphocyte, CAT, and thiol compared to the S group (p < 0.05 to p < 0.001). Dexamethasone treatment also substantially improved most measured parameters (p < 0.05 to p < 0.001), but it did not change eosinophil percentage. It was proposed that A. cepa extract could affect lung inflammation and oxidative stress in sensitized rats.


Asunto(s)
Antioxidantes , Neumonía , Ratas , Animales , Antioxidantes/farmacología , Oxidantes/metabolismo , Ovalbúmina , Cebollas/metabolismo , Dióxido de Nitrógeno/farmacología , Ratas Wistar , Neumonía/patología , Pulmón/patología , Dexametasona , Biomarcadores/metabolismo , Malondialdehído/farmacología , Compuestos de Sulfhidrilo/farmacología
19.
Physiol Rep ; 11(9): e15682, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37144592

RESUMEN

Hypothyroidism can induce oxidative stress. Nano-selenium (Nano Sel) has antioxidant effects. The current research explored Nano Sel effects on hepatic and renal oxidative damage induced by hypothyroidism in rats. Animals were grouped into (1) Control; (2) Propylthiouracil (PTU) group which received water mixed with 0.05% of PTU; (3) PTU-Nano Sel 50; (4) PTU-Nano Sel 100; and (5) PTU-Nano Sel 150. Besides PTU, the PTU-Nano Sel groups were treated with 50, 100, or 150 µg/kg of Nano Sel intraperitoneally. Treatments were done for 6 weeks. The serum level of T4, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), albumin, total protein, creatinine, and blood urea nitrogen (BUN) was evaluated. Malondialdehyde (MDA) and total thiol concentration and the activity of catalase (CAT) and superoxide dismutase (SOD) in hepatic and renal tissues also were checked. Hypothyroidism induced by PTU significantly increased AST, ALT, ALP, creatinine, BUN, and MDA concentration and noticeably reduced albumin, total protein, total thiol level, and SOD and CAT activity. Administration of Nano Sel ameliorated the adverse effects of hypothyroidism on liver and kidney function. Nano Sel applied protective effects against hepatic and renal damage resulting from hypothyroidism via ameliorating the oxidative stress status. More cellular and molecular experiments need to be done to understand the exact mechanisms.


Asunto(s)
Hipotiroidismo , Selenio , Ratas , Animales , Selenio/farmacología , Selenio/uso terapéutico , Creatinina , Ratas Wistar , Estrés Oxidativo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Hipotiroidismo/tratamiento farmacológico , Hígado/metabolismo , Riñón/metabolismo , Superóxido Dismutasa/metabolismo , Compuestos de Sulfhidrilo
20.
Meat Sci ; 202: 109198, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37130497

RESUMEN

This study aimed to evaluate a pomegranate peel extract (PPE), selected for its level of phytochemical compounds and antioxidant activities, as a nitrite substitute in dry sausages, as well as its effect on lipid and protein oxidative changes and instrumental colour during the drying period (28 days). Of the extraction solvents screened, water: acetone 3:7 (v/v) was the most effective extraction solvent, yielding extracts with the highest content of phenolic compounds, flavonoids and condensed tannins and antioxidant activities (ABTS, DPPH and FRAP). Four batches of dry sausages were produced with different incoming amounts of sodium nitrite (NaNO2) and PPE: 1) 150 ppm NaNO2; 2) 0 ppm NaNO2; 3) 0 ppm NaNO2 + 1% PPE (v/w) and 4) 0 ppm NaNO2 + 2% PPE (v/w). Nitrite removal increased lipid oxidation in uncured dry sausages, while nitrite and PPE caused lower TBA-RS values in cured and PPE treated sausages. During drying, both nitrite and PPE addition significantly decreased carbonyl and thiol contents compared to the uncured dry sausages. A dose-response was found for PPE, with lower carbonyl and thiol concentrations, the higher the level of PPE added. PPE significantly modified instrumental colour coordinates L*a*b* producing significant total colour changes compared to cured dry sausages.


Asunto(s)
Antioxidantes , Granada (Fruta) , Nitrito de Sodio/química , Extractos Vegetales/química , Compuestos de Sulfhidrilo , Lípidos
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