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1.
Amino Acids ; 54(1): 33-46, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993628

RESUMO

Sodium chlorate (NaClO3) is a common non-selective herbicide that is also used in paper and pulp mills and is produced as a by-product during drinking water disinfection by chlorine dioxide. Here, we report the effect of dietary antioxidant taurine on NaClO3-induced cytotoxicity in human red blood cells (RBC). RBC were treated with 5 mM NaClO3, either alone or in presence of 1, 2.5 and 5.0 mM taurine. Incubation of RBC with NaClO3 alone caused hemolysis, increased oxidation of lipids and proteins, methemogobin level and decreased total sulfhydryl and glutathione content. It lowered the activities of antioxidant enzymes thioredoxin reductase, glutathione peroxidase, catalase and glutathione reductase, while Cu-Zn superoxide dismutase activity was increased. The antioxidant capacity of RBC was impaired. This strongly suggests that NaClO3 causes the induction of oxidative stress condition in RBC. The specific activities of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and plasma membrane bound enzymes, were also greatly altered. However, prior treatment of RBC with taurine conferred significant protection against NaClO3-induced oxidative damage and also improved the antioxidant defence system of cells. These results were supported by electron microscopy images of RBC. Treatment with NaClO3 alone converted the normal biconcave discoidal RBC to acanthocytes and echinocytes but this transformation was greatly prevented in the presence of taurine. Thus, taurine mitigates the cytotoxicity of NaClO3 in human RBC and can function as an effective chemoprotectant.


Assuntos
Cloratos , Taurina , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Cloratos/metabolismo , Cloratos/farmacologia , Eritrócitos , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo , Taurina/metabolismo , Taurina/farmacologia
2.
Genet Res (Camb) ; 2022: 1792977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919037

RESUMO

Background: Oxidative stress is an important cause of liver disease and atherosclerosis. Natural substances with antioxidant activity are good drugs for treating liver disease and atherosclerosis. Trichosanthes kirilowii Peel Polysaccharide (TKPP) can remove DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radicals and hydroxyl free radicals in vitro, which shows antioxidant activity. Therefore, it is speculated that it can protect human hepatoma cell line (HepG2) and umbilical artery smooth muscle cell (HUASMC) against oxidative damage by hydrogen peroxide (H2O2). Methods: Oxidative damage cell models of HepG2 and HUASMC were induced by H2O2. HepG2 and HUASMC were divided into blank group, H2O2 injury group, TKPP treatment group, and glutathione (GSH) positive control group. Cell Counting Kit-8 (CCK-8) was used to detect cell viability. The level of total GSH and the amount of Nitric oxide (NO) secreted by cells were detected by specific kits. The gene and protein expressions of catalase (CAT) and superoxide dismutase (SOD) were detected by fluorescence quantitative PCR and Western Blot. Results: In these two kinds of cells, compared with the control group, the survival rate, total GSH level, and NO secretion, CAT and SOD gene and protein expressions were significantly decreased in the H2O2 damaged group. In the TKPP treatment group, the cell survival rate was significantly elevated with the increase of the polysaccharide concentration, and the total GSH level, NO secretion, CAT and SOD gene expression, and protein expression levels were also significantly increased. Conclusion: TKPP can improve the activities of HepG2 and HUASMC cells damaged by H2O2 and protect the cellular antioxidant system.


Assuntos
Aterosclerose , Trichosanthes , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glutationa/metabolismo , Glutationa/farmacologia , Humanos , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Polissacarídeos/farmacologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Trichosanthes/metabolismo
3.
Arch Ital Biol ; 160(1-2): 20-27, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913387

RESUMO

Purpose: This study aims to evaluate the changes in brain tissue and blood-brain barrier due to oxidative stress during cadmium (Cd) poisoning by biochemical, histopathological, and immunohistochemical methods. Methods: 170-190 g weighing eight-week-old female Wistar albino rats were divided into two groups (control and experimental), with 7 animals in each group. Experimental group rats were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. Biochemical, histopathological and immunohistochemical examination was performed. Results: It was seen that brain malondialdehyde (MDA) levels increased significantly, and glutathione (GSH) and catalase (CAT) activity levels decreased. In addition to degeneration in some pyramidal cells and glial cells, deformity, and picnosis in the nucleus, dilation of the meninges and cortex vessels, and inflammation around the blood vessels were observed. An increase was found in ionized calcium binding adaptor molecule 1 (IBA-1) expression in microglia cells and degenerative endothelial cells, and increased glial fibrillary acidic protein (GFAP) expression was observed in astrocytes and degenerate neurons. Conclusions: It has been shown that cadmium toxicity may cause microgliosis and astrogliogenesis by inducing cytokine production due to cell degeneration, vascularity, and inflammation in the brain cortex and by affecting microglia, astrocytes cells.


Assuntos
Cloreto de Cádmio , Intoxicação por Cádmio , Proteínas de Ligação ao Cálcio , Proteína Glial Fibrilar Ácida , Proteínas dos Microfilamentos , Animais , Encéfalo/patologia , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Intoxicação por Cádmio/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Glutationa/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Proteínas dos Microfilamentos/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar
4.
Niger J Physiol Sci ; 37(1): 83-92, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35947839

RESUMO

Arsenic compromises the gastrointestinal integrity and function via the body's anti-oxidative system breakdown.  Hence, this study aimed to investigate the effects of tocopherol on redox imbalance and histoarchitectural alterations in rats' gastrointestinal tract exposed to sodium arsenite. Sodium arsenite and graded doses of tocopherol were administered orally into experimental rats assigned to different groups for four weeks concurrently. Redox status assay was done in homogenized samples by spectrophotometry. Parietal cell mass and mucous cell density (stomach), villus height and crypt depth (ileum), goblet cells count, and crypt depth (colon) were evaluated by histomorphometry. Inflammatory cells infiltration was also assessed using a semi-quantitative procedure. Sodium arsenite caused a significant increase in Malondialdehyde and Myeloperoxidase but, decreased Superoxide dismutase, Catalase, Nitric oxide, Glutathione peroxidase, Glutathione, and Glutathione-S-Transferase. Tocopherol treatment reversed the changes (p<0.05) though not largely dose-dependent. Furthermore, tocopherol annulled sodium arsenite-induced increase in parietal cell mass and decrease in mucous cell density in the stomach, decrease in villus height and villus height/crypt depth ratio in the ileum, and decrease in goblets cells and increase in crypt depth in the colon. Moreover, activated inflammatory cell infiltration by sodium arsenite was mitigated by tocopherol. Sodium arsenite provokes not only marked inflammatory cellular infiltration but a focal loss of glands, hyperplasia of crypts, atrophic villi, and hypertrophy of Peyer's patches in the intestines, which are all lessened with tocopherol treatment.  These findings underscore the anti-oxidative properties of tocopherol as a potent dietary factor against sodium arsenite toxicity in the gastrointestinal tract. Keywords: Tocopherol, arsenic, stomach, ileum, colon.


Assuntos
Arsênio , Arsenitos , Animais , Antioxidantes/uso terapêutico , Arsênio/metabolismo , Arsênio/farmacologia , Arsenitos/toxicidade , Trato Gastrointestinal , Glutationa/metabolismo , Estresse Oxidativo , Ratos , Compostos de Sódio/toxicidade , Superóxido Dismutase/metabolismo , Tocoferóis/metabolismo , Tocoferóis/farmacologia , Vitamina E/farmacologia
5.
Oxid Med Cell Longev ; 2022: 5361241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915609

RESUMO

Ferroptosis is a type of regulated cell death that displays a promising therapeutic pathway for drug-resistant tumor cells. However, some pancreatic cancer (PC) cells are less sensitive to erastin-induced ferroptosis, and normal pancreatic cells are susceptible to this newly discovered cell death. Therefore, there is an urgent need to find drugs to enhance the sensitivity of these PC cells to erastin while limiting side effects. Here, we found that the oxidized form of vitamin C-dehydroascorbic acid (DHA) can be transported into PC cells expressing high levels of GLUT1, resulting in ferroptosis. Moreover, pharmacological vitamin C combined with erastin can synergistically induce ferroptosis of PC cells involving glutathione (GSH) reduction and ferrous iron accumulation while inhibiting the cytotoxicity of normal cells. Mechanistically, as a direct system Xc- inhibitor, erastin can directly suppress the synthesis of GSH, and the recycling of vitamin C and DHA is performed through GSH consumption, which is denoted as the classical mode. Furthermore, oxidative stress induced by erastin and vitamin C could enhance the expression of HMOX1 via the AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway to increase the labile iron level, which is named the nonclassical mode. In vivo experiments showed that erastin and vitamin C can significantly slow tumor growth in PC xenografts. In summary, the combination of erastin and vitamin C exerts a synergistic effect of classical and nonclassical modes to induce ferroptosis in PC cells, which may provide a promising therapeutic strategy for PC.


Assuntos
Ferroptose , Neoplasias Pancreáticas , Proteínas Quinases Ativadas por AMP , Ácido Ascórbico/farmacologia , Fator de Transcrição de Proteínas de Ligação GA , Glutationa/metabolismo , Heme Oxigenase-1 , Humanos , Ferro/metabolismo , Fator 2 Relacionado a NF-E2 , Fator 1 Nuclear Respiratório , Neoplasias Pancreáticas/tratamento farmacológico , Piperazinas
6.
Anal Chim Acta ; 1221: 340172, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934388

RESUMO

Glutathione (GSH) plays vital roles in a variety of biological processes, and the development of simple and effective GSH detection method is an important research topic. Herein, a multifunctional probe based on Ag&Mn:ZnInS quantum dots (QDs) was developed for bimodal imaging of GSH. MnO2, as an efficient fluorescence quencher, was in-situ grown on the surface of QDs, and then modified with hyaluronic acid (HA) to improve the stability and targeted recognition capability of the probe due to the binding between HA and CD44 receptors. After MnO2 was deconstructed by GSH, the fluorescence of the probe was recovered and the generated Mn2+ could serve as good magnetic resonance imaging (MRI) contrast agent. Moreover, the near-infrared emission probe was successfully employed in living cell and zebrafish imaging due to its low toxicity and high anti-biological interference performance. This strategy provides a simple dual-mode fluorescence/MRI imaging of GSH, which may have a broad application in biological detection.


Assuntos
Pontos Quânticos , Animais , Meios de Contraste , Fluorescência , Glutationa/metabolismo , Imageamento por Ressonância Magnética , Compostos de Manganês , Óxidos/metabolismo , Pontos Quânticos/toxicidade , Peixe-Zebra
7.
Mol Cells ; 45(8): 575-587, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35950458

RESUMO

Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron microscopy (cryo-EM) structures of human ABCB6 with its substrates, coproporphyrin III (CPIII) and hemin, at 3.5 and 3.7 Å resolution, respectively. Metalfree porphyrin CPIII binds to ABCB6 within the central cavity, where its propionic acids form hydrogen bonds with the highly conserved Y550. The resulting structure has an overall fold similar to the inward-facing apo structure, but the two nucleotide-binding domains (NBDs) are slightly closer to each other. In contrast, when ABCB6 binds a metal-centered porphyrin hemin in complex with two glutathione molecules (1 hemin: 2 glutathione), the two NBDs end up much closer together, aligning them to bind and hydrolyze ATP more efficiently. In our structures, a glycine-rich and highly flexible "bulge" loop on TM helix 7 undergoes significant conformational changes associated with substrate binding. Our findings suggest that ABCB6 utilizes at least two distinct mechanisms to fine-tune substrate specificity and transport efficiency.


Assuntos
Porfirinas , Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Microscopia Crioeletrônica , Glutationa/metabolismo , Hemina/metabolismo , Humanos , Porfirinas/metabolismo
8.
Oxid Med Cell Longev ; 2022: 2710607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936216

RESUMO

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF-α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.


Assuntos
Hepatite , Quercetina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Doxorrubicina/toxicidade , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glutationa/metabolismo , Hepatite/metabolismo , Inflamação/patologia , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar , Rutina/farmacologia , Rutina/uso terapêutico
9.
Molecules ; 27(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35956786

RESUMO

Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy.


Assuntos
Antineoplásicos , Óleos Voláteis , Pinus , Neoplasias da Próstata , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Glutationa/metabolismo , Humanos , Masculino , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Estresse Oxidativo , Pinus/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo
10.
Microb Cell Fact ; 21(1): 153, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933377

RESUMO

BACKGROUND: Glutathione is a valuable tri-peptide that is industrially produced by fermentation using the yeast Saccharomyces cerevisiae, and is widely used in the pharmaceutical, food, and cosmetic industries. It has been reported that addition of L-serine (L-Ser) is effective at increasing the intracellular glutathione content because L-Ser is the common precursor of L-cysteine (L-Cys) and glycine (Gly) which are substrates for glutathione biosynthesis. Therefore, we tried to enhance the L-Ser biosynthetic pathway in S. cerevisiae for improved glutathione production. RESULTS: The volumetric glutathione production of recombinant strains individually overexpressing SER2, SER1, SER3, and SER33 involved in L-Ser biosynthesis at 48 h cultivation was increased 1.3, 1.4, 1.9, and 1.9-fold, respectively, compared with that of the host GCI strain, which overexpresses genes involved in glutathione biosynthesis. We further examined simultaneous overexpression of SHM2 and/or CYS4 genes involved in Gly and L-Cys biosynthesis, respectively, using recombinant GCI strain overexpressing SER3 and SER33 as hosts. As a result, GCI overexpressing SER3, SHM2, and CYS4 showed the highest volumetric glutathione production (64.0 ± 4.9 mg/L) at 48 h cultivation, and this value is about 2.5-fold higher than that of the control strain. CONCLUSIONS: This study first revealed that engineering of L-Ser and Gly biosynthetic pathway are useful strategies for fermentative glutathione production by S. cerevisiase.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Vias Biossintéticas , Cisteína/metabolismo , Fermentação , Glutationa/metabolismo , Engenharia Metabólica , Fosfoglicerato Desidrogenase/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Serina
11.
Gen Physiol Biophys ; 41(4): 309-318, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35938964

RESUMO

Selenium enhances the cellular antioxidant capacity and alleviates oxidative stress. We investigated the transcriptional and enzymatic activities of selenium-dependent glutathione peroxidase 1 and thioredoxin reductase 1 (TrxR1), and levels of glutathione, hydrogen peroxide, lipid peroxides, and protein carbonyls in primary passage 5 (P5) and senescent passage 25 (P25) and 30 (P30) fibroblasts. Cells were incubated in either standard Dulbecco growth medium (CM1) containing normal plasma selenium levels (0.8 µmol/l), or in CM2, CM3, and CM4 containing 3 µmol/l (5 µmol/l for TrxR1) sodium selenite, L-hydroxyselenomethionine, or Se-methylselenocysteine, respectively. Gene transcripts and activities of both investigated enzymes as well as the levels of reduced glutathione were significantly increased in CM2-, CM3-, and CM4-incubated senescent P25 and P35 cells compared against those incubated in CM1. In congruence, although all oxidative stress parameters including oxidized glutathione were significantly lower in CM2-, CM3-, and CM4-incubated senescent cells compared against those incubated in CM1, such reductions were of significantly higher magnitude in CM3 and CM4 cells compared against those in CM2. In conclusion, organic L-hydroxyselenomethionine and Se-methylselenocysteine are equally more potent at alleviating oxidative stress in senescent cells than inorganic sodium selenite, and thus could be beneficial for use in elderly subjects and those with oxidative stress-associated disease.


Assuntos
Selênio , Idoso , Antioxidantes/metabolismo , Fibroblastos , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Estresse Oxidativo , Selênio/farmacologia , Selenito de Sódio/farmacologia , Tiorredoxina Redutase 1/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-35955076

RESUMO

BACKGROUND: Rosinidin is a flavonoid anthocyanin pigmentation found in shrub flowers such as Catharanthus roseus and Primula rosea. The molecular docking studies predicted that rosinidin has adequate structural competency, making it a viable medicinal candidate for the treatment of a wide range of disorders. The current study intends to assess rosinidin nephroprotective efficacy against nephrotoxicity induced by cisplatin in rats. MATERIALS AND METHODS: Oral acute toxicity tests of rosinidin were conducted to assess potential toxicity in animals, and it was shown to be safe. The nephroprotective effect of rosinidin 10, and 20 mg/kg were tested in rats for 25 days with concurrent administration of cisplatin. Several biochemical parameters were measured to support enzymatic and non-enzymatic oxidative stress such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH). Likewise, changes in several non-protein-nitrogenous components and blood chemistry parameters were made to support the theory linked with the pathogenesis of chemical-induced nephrotoxicity. RESULTS: Cisplatin caused significant changes in biochemical, enzymatic, and blood chemistry, which rosinidin efficiently controlled. CONCLUSIONS: The present investigation linked rosinidin with nephroprotective efficacy in experimental models.


Assuntos
Antioxidantes , Cisplatino , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Cisplatino/toxicidade , Creatinina , Glutationa/metabolismo , Rim , Simulação de Acoplamento Molecular , Estresse Oxidativo , Ratos , Superóxido Dismutase/metabolismo
13.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955707

RESUMO

SLC25A39/40, involved in mitochondrial GSH (mGSH) import from the cytoplasm, is essential for protection against oxidative stress and mitochondrial dysfunction. We examined the effects of cholestasis, through bile duct ligation (BDL) and lipopolysaccharide (LPS)-induced inflammation in mice, on Slc25a39/40 expression. Additionally, we used human clear cell renal carcinoma (KMRC-1) cells to elucidate the mechanism of regulation of SLC25A39/40 expression in the kidneys after LPS treatment. BDL resulted in a decrease in Slc25a39 mRNA in the liver and a decrease in Slc25a39/40 mRNA and protein in the kidneys. Consequently, there was a significant decrease in mGSH levels in the kidneys of BDL mice compared with those in sham mice. LPS treatment resulted in increased Slc25a40 expression in the kidneys. In KMRC-1 cells, the combination treatment of LPS-RS or FPS-ZM1 with LPS suppressed the LPS-induced increase in SLC25A40, suggesting that SLC25A40 expression could be regulated by the signaling pathway via toll-like receptor 4 and the receptor for advanced glycation end products, respectively. Our findings contribute to understanding the role of mGSH in the maintenance of the mitochondrial redox state. To the best of our knowledge, this is the first study that demonstrates the changes in Slc25a39/40 expression in mice with cholestasis-associated renal injury and LPS-induced inflammation.


Assuntos
Colestase , Lipopolissacarídeos , Animais , Ductos Biliares/metabolismo , Colestase/metabolismo , Glutationa/metabolismo , Humanos , Inflamação/patologia , Ligadura , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , RNA Mensageiro/metabolismo
14.
Eur Rev Med Pharmacol Sci ; 26(14): 5225-5232, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35916821

RESUMO

OBJECTIVE: We aimed at determining the protective effects of Pycnogenol on ethanol-induced retinotoxicity in an experimental model. MATERIALS AND METHODS: 30 male Wistar albino rats were randomly divided into three groups: an untreated healthy control (HC group), a group in which only ethanol was daily administered for six weeks (EtOH group), and a group in which ethanol + 40 mg/kg Pycnogenol was daily administered orally for six weeks (PEtOH group). The same volume (0.5 ml) of distilled water as solvent was applied in the same manner to the rats in the HC and EtOH groups. With the rats in the PEtOH and EtOH groups, 32% ethanol at a dose of 5 g/kg was administered by oral gavage one hour after the application of pycnogenol or distilled water. At the end of the experimental period, tissue samples were obtained for biochemical examination of malondialdehyde (MDA) and total glutathione (tGSH) levels, and afterwards, the eyes were removed for histopathological examination. RESULTS: Histopathological evaluations in the EtOH group showed significant destruction of retinal tissue with marked edema, decomposition and degeneration in layers, polymorphonuclear cell infiltration, dilatation and congestion in blood vessels. However, it was observed that MDA values increased and tGSH values decreased in the EtOH group. In the PEtOH group, MDA values decreased and GSH values increased. Again, degenerative changes were considerably less in this group. CONCLUSIONS:   In the light of biochemical markers and histopathological evaluations, it was observed that ethanol exposure caused a significant degeneration in the retinal tissue. It was found that Pycnogenol administration significantly reduced the destructive effects seen histopathologically. Biochemical results also coincided with other findings. It was concluded that ethanol-induced rethytosis can be prevented to a large extent by Pycnogenol administration.


Assuntos
Estresse Oxidativo , Doenças Retinianas , Animais , Antioxidantes/farmacologia , Etanol/toxicidade , Flavonoides , Glutationa/metabolismo , Masculino , Extratos Vegetais , Ratos , Ratos Wistar , Retina/metabolismo , Água
15.
BMC Cardiovasc Disord ; 22(1): 350, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918636

RESUMO

BACKGROUND: Hyperglycaemia is known to result in oxidative stress tissue injury and dysfunction. Interestingly, studies have reported hepatic and renal oxidative stress injury during prediabetes; however, any injury to the myocardium during prediabetes has not been investigated. Hence this study aims to assess changes in the myocardial tissue in an HFHC diet-induced model of prediabetes. METHODS: Male Sprague Dawley rats were randomly grouped into non-prediabetes and prediabetes (n = 6 in each group) and consumed a standard rat chow or fed a high-fat-high-carbohydrate diet respectively for a 20-week prediabetes induction period. Post induction, prediabetes was confirmed using the ADA criteria. Aldose reductase, NADH oxidase 1, superoxide dismutase, glutathione peroxide, cardiac troponins were analysed in cardiac tissue homogenate using specific ELISA kits. Lipid peroxidation was estimated by determining the concentration of malondialdehyde in the heart tissue homogenate according to the previously described protocol. Myocardial tissue sections were stained with H&E stain and analysed using Leica microsystem. All data were expressed as means ± SEM. Statistical comparisons were performed with Graph Pad instat Software using the Student's two-sided t-test. Pearson correlation coefficient was calculated to assess the association. Value of p < 0.05 was considered statistically significant. RESULTS: The prediabetes group showed a markedly high oxidative stress as indicated by significantly increased NADH oxidase 1 and malondialdehyde while superoxide dismutase and glutathione peroxide were decreased compared to non-prediabetes group. There was no statistical difference between cardiac troponin I and T in the non-prediabetes and prediabetes groups. Cardiac troponins had a weak positive association with glycated haemoglobin. CONCLUSION: The findings of this study demonstrate that prediabetes is associated with myocardial injury through oxidative stress. Future studies are to investigate cardiac contractile function and include more cardiac biomarkers.


Assuntos
Infarto do Miocárdio , Estado Pré-Diabético , Animais , Dieta Hiperlipídica/efeitos adversos , Glutationa/efeitos adversos , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , Peróxidos/efeitos adversos , Peróxidos/metabolismo , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/etiologia , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Superóxido Dismutase/metabolismo , Troponina
16.
J Trace Elem Med Biol ; 73: 127035, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35872469

RESUMO

BACKGROUND: The oxidative- and osmoregulatory stress-inducing potential of binary mixtures of sulfoxaflor (SUL), a recently developed sulfoximine insecticide, and Zn2+ was aimed to evaluate in Daphnia magna with different exposure regimes. METHODS: Animals were exposed to different SUL concentrations (1.25, 2.5, 10, and 25 mg/L) for 7 days. In vivo 48 h and in vitro effects of single and binary mixtures of SUL (25 and 50 mg/L) and Zn2+ (40 µg/L) were also determined. Furthermore, Ca2+-ATPase, oxidative stress biomarkers (catalase, CAT; superoxide dismutase, SOD; glutathione peroxidase, GPX; glutathione S-transferase, GST; reduced glutathione, GSH; thiobarbituric acid reactive substances, TBARS), and morphometric characteristics were measured. RESULTS: Variable response patterns were observed due to exposure duration and regime, toxicant type, and concentration. Marked effects of SUL were observed, especially in subacute exposure, and 25 mg/L SUL concentration can be considered as a threshold level. Stimulation of GST activity was the most typical response, followed by declined SOD activity and GSH levels. GPX activity and TBARS levels responded differently depending upon the exposure type. Subacute and in vitro effects of SUL and Zn2+ produced similar responses except for some cases. Ca2+-ATPase activity was altered differently upon subchronic duration, though inhibited by in vitro SUL+Zn effect. Subchronic SUL exposure increased body weight and length up to 25 mg/L, contrary to the observed decrease at higher concentrations. CONCLUSIONS: Single and binary mixtures of SUL and Zn2+ caused damage to the antioxidant and osmoregulatory system due to their oxidative potential on cellular targets (biomarkers). The current data emphasized that investigating the SUL toxicity with the Zn2+ combination based on the multi-biomarker approach is essential in the realistic evaluation of SUL toxicity in toxicological research.


Assuntos
Daphnia , Poluentes Químicos da Água , Adenosina Trifosfatases , Animais , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Catalase/metabolismo , Daphnia/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Estresse Oxidativo , Piridinas , Compostos de Enxofre , Superóxido Dismutase , Substâncias Reativas com Ácido Tiobarbitúrico , Poluentes Químicos da Água/análise , Zinco/farmacologia
17.
Anal Chem ; 94(29): 10470-10478, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35816734

RESUMO

Accurate diagnosis and effective treatment of malignant tumors under the interference of complex and diverse tumor microenvironments (TMEs) have become the focus of research. Herein, an innovative TME-activated biomimetic nanocatalyst with quad-modal imaging capabilities of second near-infrared (NIR-II) "turn-on" fluorescence imaging, magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal imaging (PTI) was designed and developed for self-enhanced photothermal/chemodynamic synergistic therapy. The catalyst was fabricated by loading glucose oxidase (GOD) and Ag2S quantum dots (QDs) on MnO2 nanosheets and coating them with a 4T1 cell membrane (AMG@CM), which enables them to successfully escape immune clearance and have appealing tumor-targeting ability and biocompatibility. The NIR-II fluorescence at 1130 nm of Ag2S QDs quenched by MnO2 could be recovered in vivo through the glutathione (GSH)-induced degradation of MnO2, enabling excellent TME-responsive tumor visualization. Simultaneously, the released Mn2+ can catalyze H2O2 to produce abundant hydroxyl radicals (•OH), achieving photothermal synergistically enhanced chemodynamic therapy (CDT) under NIR-II radiation. Moreover, the CDT could be self-enhanced by GOD due to the extra produced H2O2. This work demonstrates a novel and highly efficient multimodal imaging-guided integrated treatment strategy for dual-enhanced CDT tumor precise diagnosis and treatment.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Corantes , Glutationa/metabolismo , Peróxido de Hidrogênio/farmacologia , Compostos de Manganês , Imagem Multimodal , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Óxidos , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
18.
Plant Physiol Biochem ; 186: 170-181, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35868107

RESUMO

The genetic modification of plants for the removal of inorganic pollutants from contaminated soil and water bodies is an emerging area for addressing environmental concerns. This approach is based on the ability of plants to take up and accumulate heavy metals, with efficiency being dependent on the underlying mechanisms of heavy metal accumulation and tolerance. A robust antioxidant pathway is determinantal for heavy metal uptake and accumulation and, therefore, in this study, we evaluated the transgenic tomato plants installed with Ascorbate Glutathione (ASA-GSH) pathway genes for uptake, accumulation, and response to mercury (Hg). We observed that ASA-GSH overexpressing lines were resilient to Hg stress as they displayed higher photosynthetic activity and increased photosynthetic gas exchange parameters with a concomitant decrease in ion leakage under Hg stress. Additionally, transgenic lines accumulated high osmolytes and showed enhanced activity of antioxidant enzymes. Moreover, the results of SEM and confocal microscopy confirmed least damage to plant tissue in ASA-GSH overexpressing lines compared to wild-type under Hg-stress which was further supported by Atomic absorption study that revealed a significant decline in Hg accumulation in the leaves of transgenic lines compared to wild-type under stress conditions. In conclusion, pyramiding of ASA-GSH pathway genes in tomato plants is an efficient approach for the development of Hg-resistant tomato plants and the reclamation of Hg-contaminated sites.


Assuntos
Lycopersicon esculentum , Mercúrio , Metais Pesados , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Glutationa/metabolismo , Lycopersicon esculentum/genética , Lycopersicon esculentum/metabolismo , Metais Pesados/metabolismo , Estresse Oxidativo , Plantas Geneticamente Modificadas/genética
19.
Environ Toxicol Pharmacol ; 94: 103936, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35878806

RESUMO

We compared the antioxidant activity of serum and plasma samples of a known glutathione content with the activity of glutathione, whilst determining to what extent various stress factors might change the activity of the tested samples. Copper ions and benzene were used as examples of environmental stress factors, and xenobiotics in the form of representatives of various groups of drugs, were used as examples of pharmacological stressors at therapeutic ranges. The activity was assessed by the ABTS, ORAC, FRAP and CUPRAC methods. Glutathione content was measured by the HPLC-FD method. During the experiments, plasma samples were shown to be more resistant to oxidative stress. Moreover, the important role of environmental xenobiotics in oxidative stress was revealed, as well as the differentiated influence of pharmaceutical xenobiotics. Among all pharmaceutical xenobiotics tested, including representatives of antiarrhythmic, antiepileptic, cytostatic and mucolytic drugs, the greatest stress was shown for antiarrhythmic drugs and cytostatics.


Assuntos
Antioxidantes , Xenobióticos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glutationa/metabolismo , Estresse Oxidativo , Soro/metabolismo
20.
Int J Biol Sci ; 18(11): 4545-4559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864954

RESUMO

Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C+MHCIIhigh DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.


Assuntos
Células Dendríticas , Glutationa , Ácido Litocólico , Receptores Acoplados a Proteínas G , Ácidos e Sais Biliares/metabolismo , Células Dendríticas/metabolismo , Glutationa/metabolismo , Humanos , Ácido Litocólico/farmacologia , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais
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