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1.
Food Chem Toxicol ; 160: 112801, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34974130

RESUMO

In this research retrieval effects of natural yellow (NY) on the performance of carmoisine (CAR) inhibited bovine liver catalase (BLC) was studied using multispectral and theoretical methods. Kinetic studies showed that CAR inhibited BLC through competitive inhibition (IC50 value of 2.24 × 10-6 M) while the addition of NY recover the activity of CAR-BLC up to 82% in comparison with the control enzyme. Circular dichroism data revealed that NY can repair the structural changes of BLC, affected by CAR. Furthermore, an equilibrium dialysis study indicated that NY could reduce the stability of the CAR-catalase complex. The surface plasmon resonance (SPR) data analysis indicated a high affinity of NY to BLC compared to CAR and the binding of NY led to a decrease in the affinity of the enzyme to the inhibitor. On the other hand, fluorescence and molecular docking studies showed that the quenching mechanism of BLC by CAR occurs through a static quenching process, and van der Waals forces and hydrogen bonding play a crucial role in the binding of CAR to BLC. MLSD data demonstrated that NY could increase the binding energy of CAR-BLC complex from -7.72 kJ mol-1 to -5.9 kJ mol-1, leading to complex instability and catalase activity salvage.


Assuntos
Catalase/antagonistas & inibidores , Catalase/química , Curcumina/química , Corantes de Alimentos/química , Naftalenossulfonatos/química , Animais , Bovinos , Dicroísmo Circular , Proposta de Concorrência , Ligação de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Ressonância de Plasmônio de Superfície
2.
Chem Biodivers ; 19(1): e202100724, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34773377

RESUMO

To complement the knowledge on the anti-inflammatory activity of methyl and isopropyl N-methylanthranilates, two natural products with panacea-like properties, we investigated their effects on thioglycolate-elicited macrophages by evaluating macrophage ability to metabolize MTT, macrophage membrane function, and macrophage myeloperoxidase and phagocytic activities. Moreover, two additional aspects of the inflammatory response of these compounds, their inhibitory activity on xanthine oxidase and catalase, were studied. It was found that these two compounds regulate elicited macrophage functions, most probably by interfering with the function of cell membranes and changing the reducing cellular capacity or enzyme activity of macrophages. Nonetheless, no significant inhibitory action either towards xanthine oxidase or catalase was found, suggesting that the inhibition of these enzymes is not involved in the anti-inflammatory mode of action of these two esters.


Assuntos
Fagocitose/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Catalase/antagonistas & inibidores , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , ortoaminobenzoatos/química , ortoaminobenzoatos/metabolismo
3.
Bull Exp Biol Med ; 171(5): 606-610, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34617179

RESUMO

In a relatively isolated system of avian embryo, the metabolism of NO, a component of the dinitrosyl iron complexes (DNIC), the main NO donor in most tissues, depends on the ligands that make up the complex. This fact corroborates the earlier hypothesis that these ligands perform a regulatory function in NO metabolism. It is also shown that nitrite injected into the embryo is not oxidized to nitrate like NO in DNIC, but is accumulated outside the amniotic sac. Normally, nitrite is present in an embryo in trace amounts. These facts suggest that NO in the embryo is transferred from the donor molecule to a target in the embryo tissues further transformed with minimum oxidation to nitrite.


Assuntos
Quelantes de Ferro/farmacologia , Ferro/metabolismo , Ferro/farmacologia , Óxidos de Nitrogênio/metabolismo , Óxidos de Nitrogênio/farmacologia , Animais , Catalase/antagonistas & inibidores , Catalase/efeitos dos fármacos , Catalase/metabolismo , Embrião de Galinha , Ácido Cítrico/farmacologia , Desenvolvimento Embrionário/efeitos dos fármacos , Glutationa , Hemoglobinas/química , Hemoglobinas/metabolismo , Hemoglobinas/farmacologia , Ferro/química , Ferro/fisiologia , Quelantes de Ferro/metabolismo , Ligantes , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/metabolismo , Nitritos/metabolismo , Óxidos de Nitrogênio/química , Oxirredução/efeitos dos fármacos , Fenantrolinas/farmacologia
4.
Cells ; 10(9)2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34572113

RESUMO

The increased level of hydrogen peroxide accompanies some modes of macrophage specification and is linked to ROS-based antimicrobial activity of these phagocytes. In this study, we show that activation of toll-like receptors with bacterial components such as LPS is accompanied by the decline in transcription of hydrogen peroxide decomposing enzyme-catalase, suppression of which facilitates the polarization of human macrophages towards the pro-inflammatory phenotype. The chromatin remodeling at the CAT promoter involves LSD1 and HDAC1, but activity of the first enzyme defines abundance of the two proteins on chromatin, histone acetylation status and the CAT transcription. LSD1 inhibition prior to macrophage activation with LPS prevents CAT repression by enhancing the LSD1 and interfering with the HDAC1 recruitment to the gene promoter. The maintenance of catalase level with LSD1 inhibitors during M1 polarization considerably limits LPS-triggered expression of some pro-inflammatory cytokines and markers such as IL1ß, TNFα, COX2, CD14, TLR2, and IFNAR, but the effect of LSD1 inhibitors is lost upon catalase deficiency. Summarizing, activity of LSD1 allows for the CAT repression in LPS stimulated macrophages, which negatively controls expression of some key pro-inflammatory markers. LSD1 inhibitors can be considered as possible immunosuppressive drugs capable of limiting macrophage M1 specialization.


Assuntos
Catalase/antagonistas & inibidores , Histona Desacetilase 1/metabolismo , Histona Desmetilases/metabolismo , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Receptores Toll-Like/metabolismo , Catalase/genética , Catalase/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Histona Desacetilase 1/genética , Histona Desmetilases/genética , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Transdução de Sinais , Receptores Toll-Like/genética , Fator de Necrose Tumoral alfa/metabolismo
5.
Genetics ; 218(2)2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34027548

RESUMO

Hydrogen peroxide (H2O2, HP) is a universal toxin that organisms deploy to kill competing or invading cells. Bactericidal action of H2O2 presents several questions. First, the lethal H2O2 concentrations in bacterial cultures are 1000x higher than, for example, those calculated for the phagosome. Second, H2O2-alone kills bacteria in cultures either by mode-one, via iron-mediated chromosomal damage, or by mode-two, via unknown targets, but the killing mode in phagosomes is unclear. Third, phagosomal H2O2 toxicity is enhanced by production of nitric oxide (NO), but in vitro studies disagree: some show NO synergy with H2O2 antimicrobial action, others instead report alleviation. To investigate this "NO paradox," we treated Escherichia coli with various concentrations of H2O2-alone or H2O2+NO, measuring survival and chromosome stability. We found that all NO concentrations make sublethal H2O2 treatments highly lethal, via triggering catastrophic chromosome fragmentation (mode-one killing). Yet, NO-alone is not lethal, potentiating H2O2 toxicity by blocking H2O2 scavenging in cultures. Catalases represent obvious targets of NO inhibition, and catalase-deficient mutants are indeed killed equally by H2O2-alone or H2O2+NO treatments, also showing similar levels of chromosome fragmentation. Interestingly, iron chelation blocks chromosome fragmentation in catalase-deficient mutants without blocking H2O2-alone lethality, indicating mode-two killing. In fact, mode-two killing of WT cells by much higher H2O2 concentrations is transiently alleviated by NO, reproducing the "NO paradox." We conclude that NO potentiates H2O2 toxicity by promoting mode-one killing (via catastrophic chromosome fragmentation) by otherwise static low H2O2 concentrations, while transiently suppressing mode-two killing by immediately lethal high H2O2 concentrations.


Assuntos
Catalase/antagonistas & inibidores , Cromossomos Bacterianos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Óxido Nítrico/farmacologia , Animais , Catalase/metabolismo , Bovinos , Cromossomos Bacterianos/genética , Fragmentação do DNA/efeitos dos fármacos , Reparo do DNA , Sinergismo Farmacológico , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética
6.
Drug Des Devel Ther ; 15: 1157-1165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33731987

RESUMO

AIM: Long-term ketamine use is known to create an interstitial cystitis-like problem in the bladder. It is known that long-term intermittent ketamine is applied to the children receiving radiotherapy for sedation. This study was planned to investigate whether this effect seen in the bladder causes similar changes in the kidneys, testicles, epididymis and ductus deferens. MATERIALS AND METHODS: A total of 12 male Wistar Albino rats for 3 weeks were used in the study. Rats were divided equally into 2 groups as, ketamine and saline. 50 mg/kg ketamine was administered intraperitoneally during 21 days to ketamine (K) groups. 1mL/kg saline was administered intraperitoneally during 21 days to saline (S) groups. At the end of 21 days kidney and testicular tissues were taken for biochemical and histopathological evaluations. RESULTS: Histological assessment of kidney tissue showed that tubule epithelial congestion increased significantly in the ketamine group. Epididymis congestion and distortion in the epididymal gland were found to be different in the ketamine group when testicular tissue was examined. Thiobarbituric acid reactive substances (TBARS) level in testicular and kidney tissue was found to be significantly higher in the ketamine group according to the saline group. Catalase (CAT) enzyme activity was significantly lower in the ketamine group compared to the saline group in both tissues. Paraoxonase-1 (PON-1) enzyme activity was significantly higher in the ketamine group compared to the saline group. CONCLUSION: We think that the results we have achieved in this study will provide guidance on ketamine, which is repeated in daily anesthesia applications, especially in radiation oncology. But these findings should be supported by clinical and experimental studies that will be conducted in a more detailed and broad series.


Assuntos
Ketamina/farmacologia , Rim/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Arildialquilfosfatase/metabolismo , Catalase/antagonistas & inibidores , Catalase/metabolismo , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Ketamina/administração & dosagem , Rim/metabolismo , Masculino , Ratos , Ratos Wistar , Testículo/metabolismo
7.
Anticancer Agents Med Chem ; 21(17): 2419-2428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33563160

RESUMO

BACKGROUND: We previously synthesized two DNA intercalative Pyrimido[4',5':4,5]thieno(2,3-b) quinolines (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4',5':4,5]thieno(2,3-b) quinolines (Hydroxy- DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino) pyrimido[4',5':4,5]thieno(2,3-b) quinolines (Methoxy-DPTQ), and reported their cytotoxicity against cancer cell lines. METHODS: In the present study, we sought to analyze the antitumor activity of Hydroxy-DPTQ and Methoxy-DPTQ on Ehrlich's ascites carcinoma in vivo models, along with other pharmacological activities and toxicity. RESULTS: In this study, both the test molecules studied possess potent in vivo antitumor activity without any hematological, biochemical or nephrotoxicity. Significant tumor regression was observed after treatment with both the test molecules, which is suggested by the decrease in the bodyweight of tumour-bearing mice. Mean survival time of mice with tumor was increased from 16 days to 25 and 29 days after 40 and 80 mg/kg Hydroxy- DPTQ treatment, respectively, with a similar result for Methoxy-DPTQ. A dose-dependent increase in lifespan up to 80-85% was also displayed by both Hydroxy-DPTQ and Methoxy-DPTQ. Reduction in the tumor volume of mice, upon treatment with molecules also confirmed their antitumor activity. These molecules also exhibited pharmacological activities such as antioxidant, anti-inflammatory and analgesic activities. Administration of Hydroxy-DPTQ and Methoxy-DPTQ not only reduced the level of lipid peroxidation in tumor bearing mice but also restored the superoxide dismutase, glutathione, and catalase levels to normal, substantiating the antioxidant property. Also, treatment of Hydroxy-DPTQ and Methoxy-DPTQ inhibited the pain to approximately 60-80% and 19-33%, respectively. Further, the treatment with Hydroxy-DPTQ and Methoxy-DPTQ reversed the abnormality in the RBC, WBC and haemoglobin levels, and gentamicin induced nephrotoxicity. CONCLUSION: Hydroxy-DPTQ and Methoxy-DPTQ are good antitumor molecules with pharmacological properties.


Assuntos
Analgésicos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Dor/tratamento farmacológico , Ácido Acético , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Carcinoma de Ehrlich/patologia , Catalase/antagonistas & inibidores , Catalase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Dor/induzido quimicamente , Manejo da Dor , Ratos , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo
8.
Molecules ; 26(3)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535575

RESUMO

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Indóis/farmacologia , Quinolinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Carcinoma de Ehrlich/enzimologia , Carcinoma de Ehrlich/patologia , Catalase/antagonistas & inibidores , Feminino , Técnicas In Vitro , Indóis/química , Camundongos , Quinolinas/química , Superóxido Dismutase/antagonistas & inibidores , Inibidores da Topoisomerase II/farmacologia , Células Tumorais Cultivadas
9.
PLoS One ; 16(2): e0245799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606716

RESUMO

Peroxisomes are metabolically active organelles which are known to exert anti-inflammatory effects especially associated with the synthesis of mediators of inflammation resolution. However, the role of catalase and effects of peroxisome derived reactive oxygen species (ROS) caused by lipid peroxidation through 4-hydroxy-2-nonenal (4-HNE) on lipopolysaccharide (LPS) mediated inflammatory pathway are largely unknown. Here, we show that inhibition of catalase by 3-aminotriazole (3-AT) results in the generation of peroxisomal ROS, which contribute to leaky peroxisomes in RAW264.7 cells. Leaky peroxisomes cause the release of matrix proteins to the cytosol, which are degraded by ubiquitin proteasome system. Furthermore, 3-AT promotes the formation of 4HNE-IκBα adduct which directly interferes with LPS induced NF-κB activation. Even though, a selective degradation of peroxisome matrix proteins and formation of 4HNE- IκBα adduct are not directly related with each other, both of them are could be the consequences of lipid peroxidation occurring at the peroxisome membrane.


Assuntos
Catalase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Lipopolissacarídeos/farmacologia , Peroxissomos/efeitos dos fármacos , Peroxissomos/metabolismo , Animais , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Camundongos , NF-kappa B/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , Células RAW 264.7 , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo
10.
J Trace Elem Med Biol ; 65: 126719, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33517023

RESUMO

BACKGROUND: Bivalves can accumulate and concentrate most pollutants, even if they are present in somewhat low concentrations. The present study aimed to use freshwater bivalveas for the first time as vital indicator for silver/chitosan nanocomposites (Ag-CS NCs) in the freshwater environment. METHODS: Following the preparation and characterization of Ag-CS NCs by using UV-vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, the animals exposed to three different dose of nano chitosan (CS), AgNPs, and Ag-CS NCs (12.5, 25 and 50 mg/L) for consecutive 6 days. RESULTS: Ag-CS particles were in size range of 8-19 nm. The nominal concentrations for Ag-CS NCs were 12.5, 25 and 50 mg Ag L-1 were corresponding to measured concentration of AgNPs 0.37, 0.81, and 1.65 mg Ag L-1, respectively. All concentrations of Ag-CS NCs caused a significant increase in MDA and NO, while GSH and CAT levels decreased significantly in all organs. Histological investigation of the gills, labial palp and foot tissues showed alternation after exposure to Ag-CS NCs, especially at dose 50 mg/L. CONCLUSION: The present study showed that exposure to Ag-CS NCs caused oxidative stress responses in Coelatura aegyptiaca and histological changes in the organs. These physiological and histological changes observed after exposure to Ag-CS NCs were most likely the result of the action of AgNPs themselves while the effect of chitosan on these changes was negligible. We concluded that Coelatura aegyptiaca was a sensitive bio-indicator for monitoring of the past and the present water pollution by nanoparticles.


Assuntos
Bivalves/efeitos dos fármacos , Quitosana/farmacologia , , Brânquias/efeitos dos fármacos , Nanocompostos/química , Prata/farmacologia , Animais , Catalase/antagonistas & inibidores , Catalase/metabolismo , Quitosana/química , Relação Dose-Resposta a Droga , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Prata/química
11.
Int J Biol Macromol ; 171: 225-233, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33418042

RESUMO

Polycyclic aromatic hydrocarbons, distributing extensively in the soil, would potentially threaten the soil organisms (Eisenia fetida) by triggering oxidative stress. As a ubiquitous antioxidant enzyme, catalase can protect organisms from oxidative damage. To reveal the potential impact of polycyclic aromatic hydrocarbon pyrene (Pyr) on catalase (CAT) and the possible protective effect of Ascorbic acid (vitamin C), multi-spectral and molecular docking techniques were used to investigate the influence of structure and function of catalase by pyrene. Fluorescence and circular dichroism analysis showed that pyrene would induce the microenvironmental changes of CAT amino acid residues and increase the α-helix in the secondary structure. Molecular simulation results indicated that the main binding force of pyrene around the active center of CAT is hydrogen bonding force. Furthermore, pyrene inhibited catalase activity to 69.9% compared with the blank group, but the degree of inhibition was significantly weakened after vitamin C added into the research group. Cell level experiments showed that pyrene can increase the level of ROS in the body cavity cell of earthworms, and put the cells under the threat of potential oxidative damage. Antioxidants-vitamin C has a protective effect on catalase and maintains the stability of intracellular ROS levels to a certain extent.


Assuntos
Ácido Ascórbico/farmacologia , Catalase/antagonistas & inibidores , Oligoquetos/efeitos dos fármacos , Pirenos/toxicidade , Poluentes do Solo/toxicidade , Aminoácidos/química , Animais , Antioxidantes/farmacologia , Catalase/química , Dicroísmo Circular , Ligação de Hidrogênio , Modelos Moleculares , Simulação de Acoplamento Molecular , Oligoquetos/enzimologia , Estresse Oxidativo , Conformação Proteica , Estrutura Secundária de Proteína , Pirenos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Poluentes do Solo/farmacologia , Espectrometria de Fluorescência , Eletricidade Estática
12.
Mikrochim Acta ; 187(12): 656, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188446

RESUMO

Elevated amounts of reactive oxygen species (ROS) including hydrogen peroxide (H2O2) are observed in the epidermis in different skin disorders. Thus, epidermal sensing of H2O2 should be useful to monitor the progression of skin pathologies. We have evaluated epidermal sensing of H2O2 in vitro, by visualising H2O2 permeation through the skin. Skin membranes were mounted in Franz cells, and a suspension of Prussian white microparticles was deposited on the stratum corneum face of the skin. Upon H2O2 permeation, Prussian white was oxidised to Prussian blue, resulting in a pattern of blue dots. Comparison of skin surface images with the dot patterns revealed that about 74% of the blue dots were associated with hair shafts. The degree of the Prussian white to Prussian blue conversion strongly correlated with the reciprocal resistance of the skin membranes. Together, the results demonstrate that hair follicles are the major pathways of H2O2 transdermal penetration. The study recommends that the development of H2O2 monitoring on skin should aim for pathway-specific epidermal sensing, allowing micrometre resolution to detect and quantify this ROS biomarker at hair follicles.Graphical abstract.


Assuntos
Epiderme/metabolismo , Peróxido de Hidrogênio/farmacocinética , Pele/metabolismo , Animais , Biomarcadores/metabolismo , Técnicas Biossensoriais , Catalase/antagonistas & inibidores , Ferrocianetos/química , Microscopia Eletrônica de Varredura , Neovascularização Fisiológica , Espécies Reativas de Oxigênio/metabolismo , Pele/enzimologia , Suínos , Cicatrização
13.
Biomed Res Int ; 2020: 5085369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33150175

RESUMO

As potential inhibitors target to biological enzymes, antibiotics may have certain impacts on the biochemical treatment process. With micrococcus catalase (CAT) served as the target molecule, the impact and inhibition mechanism for typical tetracyclines (TCs) were evaluated. Toxicity experiments showed that TCs had significant inhibition on CAT in the sequence of tetracycline>chlortetracycline>oxytetracycline>doxycycline. To clarify the inhibition mechanism between TCs and CAT which was explored with the assistance of fluorescence spectroscopy and MOE molecule simulation. According to fluorescence analysis, TCs quenched the fluorescence signal of CAT by the mode of static quenching. Combined with toxicity data, it could be presumed that TCs combined with the catalytic active center and thus inhibited CAT. Above presumption was further verified by the molecular simulation data. When TCs combined with the catalytic center of CAT, the compounds have increased combination areas and prominent energy change (compared with the compounds formed by TCs and noncatalytic center recommend by MOE software). IBM SPSS statistics showed that TC toxicity positively correlated with the hydrogen bonds such as O13→Glu252, O1←Arg195, and O6→Asp249, but negatively correlated with the hydrogen bonds such as O10→Pro363, O10→Lys455, and O12 â†’ Asn127. TC toxicity also positively correlated with the ion bonds ofN4-Glu252, but negatively correlated with the ion bonds of N4-Asp379. Hydrogen bonds and ion bonds for above key sites were closely related to the inhibition effect of TCs on CAT.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Catalase/antagonistas & inibidores , Clortetraciclina/química , Doxiciclina/química , Inibidores Enzimáticos/química , Oxitetraciclina/química , Tetraciclina/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Catalase/química , Catalase/genética , Catalase/metabolismo , Domínio Catalítico , Clortetraciclina/metabolismo , Doxiciclina/metabolismo , Inibidores Enzimáticos/metabolismo , Ligação de Hidrogênio , Micrococcus/química , Micrococcus/enzimologia , Simulação de Acoplamento Molecular , Oxitetraciclina/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Espectrometria de Fluorescência , Tetraciclina/metabolismo
14.
J Am Chem Soc ; 142(49): 20735-20743, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33237755

RESUMO

Depression is intimately linked with oxidative stress in the brains. Peroxisome plays vital roles in the regulation of intracellular redox balance by keeping reactive oxygen species (ROS) homeostasis. Available evidence indicates a possible relationship between peroxisomal ROS and depression. Even so, the underlying modulation mechanisms of peroxisomal ROS in depression are still rudimentary due to the limitations of the existing detecting methods. Hence, we developed a two-photon fluorescent probe TCP for the real-time visualization of the first produced ROS superoxide anion radical (O2•-) in peroxisome. Using the two-photon fluorescence imaging, we found that peroxisomal O2•- rose during oxidative stress in the mouse brains, resulting in the inactivation of catalase (CAT). Subsequently, the intracellular H2O2 level elevated, which further oxidized tryptophan hydroxylase-2 (TPH2). Then the decrease contents of TPH2 caused the dysfunction of 5-hydroxytryptamine (5-HT) system in the mouse brains, eventually leading to depression-like behaviors. Our work provides evidence of a peroxisomal O2•- mediated signaling pathway in depression, which will conduce to pinpoint potential targets for the treatment of depression.


Assuntos
Encéfalo/metabolismo , Depressão/patologia , Estresse Oxidativo , Superóxidos/metabolismo , Triptofano Hidroxilase/metabolismo , Animais , Encéfalo/patologia , Catalase/antagonistas & inibidores , Catalase/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Peróxido de Hidrogênio/metabolismo , Camundongos , Microscopia de Fluorescência , Células PC12 , Peroxissomos/metabolismo , Ratos , Serotonina/metabolismo
15.
Toxicol In Vitro ; 69: 104996, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32898619

RESUMO

Oxidative stress biomarkers are powerful endpoints in toxicological research. Cellular reductive/oxidative balance affects numerous signaling pathways involving H2O2. Detoxification and control of H2O2 levels results mainly from catalase activity. The aim of this work was to develop a precise, simple, cost-effective microassay to measure catalase activity in small tissue samples and cell extracts. We developed a protocol that quantifies H2O2 decomposition by intrinsic catalase in biological samples. Catalase activity was calculated based on rate of decomposition of H2O2, following absorbance at 240 nm. We developed a multi-well spectroscopic approach, reducing sample quantity requirements and allowing simultaneous assessment of large number of samples. The protocol is sensitive across a wide range of catalase activity (11.5-7575 U). The assay presents a 95% confidence interval with an intra-assay coefficient of variation of 3.7%, an inter-assay coefficient of variation of 6.2% and good correlation with a commercial kit. The assay was established and validated for different biological samples, including sheep hepatic tissue and human tumor and non-tumor cell lines. This high-throughput method is robust, sensitive, time-saving and cost-effective, generating highly reproducible results with precision and good correlation with a commercial kit reinforcing the method's validity for research and toxicological applications.


Assuntos
Bioensaio , Catalase/metabolismo , Ensaios de Triagem em Larga Escala , Animais , Catalase/antagonistas & inibidores , Células Hep G2 , Humanos , Peróxido de Hidrogênio/farmacologia , Cinética , Fígado/metabolismo , Rotenona/farmacologia , Ovinos , Vitamina K 3/farmacologia , terc-Butil Hidroperóxido/farmacologia
16.
J Tradit Chin Med ; 40(3): 473-483, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32506863

RESUMO

OBJECTIVE: To explore the total phenolic and flavonoid content, enzymatic, non-enzymatic antioxidant properties, anti-inflammation and anticancer activities of hexane, ethyl acetate and methanol extracts of Floscopa scandens (F. scandens). METHODS: Non-enzymatic antioxidant activity was examined by 2, 2-diphenyl-1-picrylhydrazyl assay, nitric oxide scavenging assay, hydroxyl radical scavenging assay, reducing power assay, hydrogen peroxide scavenging assay, superoxide scavenging assay and metal chelating assay. Enzymatic antioxidant ability was screened for the antioxidant enzymes such as ascorbate oxidase, peroxidase, catalase and polyphenol oxidase. The anti-inflammatory property was proved with the inhibition of protein denaturation and protease inhibitory assays. In vitro anticancer activity was assessed by cell viability assay. RESULTS: Methanol extract contained high amount of phenols (198.41 mg catechol equivalent/gram extract) and flavonoids (101.70 mg quercetin equivalent/gram extract) showed higher activity than hexane and ethyl acetate extracts in all experiments. Fresh plant showed considerable enzymatic antioxidant activity. CONCLUSION: The results revealed that the methanol extracts of F. scandens could be used as a potential source of antioxidant, anti-inflammatory and anticancer bioactive compounds.


Assuntos
Anti-Inflamatórios/química , Antineoplásicos/química , Antioxidantes/química , Commelinaceae/química , Inibidores Enzimáticos/química , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Ascorbato Oxidase/antagonistas & inibidores , Ascorbato Oxidase/química , Catalase/antagonistas & inibidores , Catalase/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Humanos , Peroxidase/antagonistas & inibidores , Peroxidase/química , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Quercetina/química , Quercetina/farmacologia
17.
Hypertens Res ; 43(11): 1192-1203, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32461634

RESUMO

Intracerebroventricular (icv) injection of hydrogen peroxide (H2O2) or the increase of endogenous H2O2 centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with H2O2 injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5-10/group) with stainless steel cannulas implanted in the lateral ventricle were used. In freely moving rats, H2O2 (5 µmol/1 µl) or ATZ (5 nmol/1 µl) icv reduced the pressor responses to ANG II (50 ng/1 µl) icv in SHRs (11 ± 3 and 17 ± 4 mmHg, respectively, vs. 35 ± 6 mmHg) and 2K1C hypertensive rats (3 ± 1 and 16 ± 3 mmHg, respectively, vs. 26 ± 2 mmHg). ATZ (3.6 mmol/kg of body weight) iv alone or combined with H2O2 icv also reduced icv ANG II-induced pressor response in SHRs and 2K1C hypertensive rats. Baseline arterial pressure was also reduced (-10 to -15 mmHg) in 2K1C hypertensive rats treated with H2O2 icv and ATZ iv alone or combined and in SHRs treated with H2O2 icv alone or combined with ATZ iv. The results suggest that exogenous or endogenous H2O2 acting centrally produces anti-hypertensive effects impairing central pressor mechanisms activated by ANG II in SHRs or 2K1C hypertensive rats.


Assuntos
Amitrol (Herbicida)/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Peróxido de Hidrogênio/administração & dosagem , Hipertensão/tratamento farmacológico , Oxidantes/administração & dosagem , Angiotensina II , Animais , Catalase/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos , Infusões Intraventriculares , Masculino , Ratos Endogâmicos SHR
18.
Comb Chem High Throughput Screen ; 23(9): 972-980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294033

RESUMO

AIM AND OBJECTIVE: Humans continuously use pesticides in the field to control the pest population and weeds for considerable agricultural productivity. Side-by species like grazinganimals, insects and other species are adversely affected by or become resistant to pesticides. Insects, birds and cattle are highly abundant dwellers of the agriculture-field and represent three distinct phyla having versatile physiological features. Besides higher agricultural-productivity, protection to several species will maintain ecological/environmental balance. Studies on the effect of widely used pesticides on their DNA-stability and important enzymatic-activities are insufficient. MATERIALS AND METHODS: Antioxidant-activity (Superoxide-dismutase; SOD/Catalase- by gelzymogram- assay) and DNA-stability (fragmentation-assay) in hepatic/gut tissues were studied after in vitro exposure of Chlorpyrifos, Fenvalerate, Nimbecidine or Azadirachtin to goat/cow/poultry-hen/insect. RESULTS: In general, all pesticides were found to impair enzymatic-activities. However, lower organisms were affected more than higher vertebrates by azadirachtin-treatment. DNA fragmentation was found more in insects/poultry-birds than that of the cattle in hepatic/gut tissues. Inversely, toxicity/antioxidant marker-enzymes were more responsive in insect gut-tissues. However, mitochondrialtoxicity revealed variable effects on different species. It has been noticed that chlorpyrifos is the most toxic pesticide, followed by Fenvalerate/Nimbecidine (Azadirachtin, AZT). Nevertheless, AZT revealed its higher DNA-destabilizing effects on the field-insects as compared to the other animals. CONCLUSION: Field-insects are highly integrated into the ecosystem and the local bio-geo-chemical cycle, which may be impaired. Pesticides may have toxic effects on higher vertebrates and may sustain in the soil after being metabolized into their different derivatives. Some of the sensitive biochemical parameters of this organism may be used as a biomarker for pesticide toxicity.


Assuntos
Antioxidantes/farmacologia , Catalase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/farmacologia , Superóxido Dismutase/antagonistas & inibidores , Animais , Antioxidantes/toxicidade , Bovinos , Galinhas , Clorpirifos/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Ecossistema , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/toxicidade , Instabilidade Genômica/efeitos dos fármacos , Cabras , Insetos , Limoninas/farmacologia , Gado , Nitrilas/farmacologia , Noresteroides/farmacologia , Praguicidas/toxicidade , Piretrinas/farmacologia
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