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1.
Nat Commun ; 11(1): 5104, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037214

RESUMO

Many intestinal pathogens, including Clostridioides difficile, use mucus-derived sugars as crucial nutrients in the gut. Commensals that compete with pathogens for such nutrients are therefore ecological gatekeepers in healthy guts, and are attractive candidates for therapeutic interventions. Nevertheless, there is a poor understanding of which commensals use mucin-derived sugars in situ as well as their potential to impede pathogen colonization. Here, we identify mouse gut commensals that utilize mucus-derived monosaccharides within complex communities using single-cell stable isotope probing, Raman-activated cell sorting and mini-metagenomics. Sequencing of cell-sorted fractions reveals members of the underexplored family Muribaculaceae as major mucin monosaccharide foragers, followed by members of Lachnospiraceae, Rikenellaceae, and Bacteroidaceae families. Using this information, we assembled a five-member consortium of sialic acid and N-acetylglucosamine utilizers that impedes C. difficile's access to these mucosal sugars and impairs pathogen colonization in antibiotic-treated mice. Our findings underscore the value of targeted approaches to identify organisms utilizing key nutrients and to rationally design effective probiotic mixtures.


Assuntos
Clostridium difficile/patogenicidade , Microbioma Gastrointestinal/fisiologia , Monossacarídeos/metabolismo , Acetilglucosamina/metabolismo , Animais , Antibacterianos , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Separação Celular/métodos , Infecções por Clostridium/microbiologia , Clostridium difficile/genética , Clostridium difficile/crescimento & desenvolvimento , Deutério , Feminino , Mucinas Gástricas/química , Mucinas Gástricas/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Metagenoma , Camundongos Endogâmicos C57BL , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Análise Espectral Raman
2.
Toxicol Lett ; 334: 66-77, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002524

RESUMO

Although colchicine (COL) has been used to treat gout for more than a thousand years, it has been shrouded in a dark history for a long time due to its high toxicity, especially for the gastrointestinal tract. With the widespread clinical application of COL, COL's toxicity to the gastrointestinal tract has raised concerns. This study's objective was to address the exact intestinal toxicity of COL, with particular attention to the effects of COL on gut microbiota homeostasis. The mice were exposed to various dosages of COL (0.1, 0.5, and 2.5 mg kg-1 body weight per day) for a week, and the results showed that COL exposure caused serious intestinal injuries, reducing the relative expression levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and tight junction proteins (zo-1, claudin-1, and occludin) in the ileum and colon tissue. The 16S rRNA gene sequencing analysis of mice feces samples revealed that the composition and diversity of intestinal microbiome underwent a profound remodeling at the dosage of 2.5 mg kg-1 body weight per day, which may increase the toxic load in the gut. In addition, elevated levels of diamine oxidase (DAO) and lipopolysaccharide (LPS) in serum indicated that COL increased intestinal permeability, impairing intestinal barrier. In conclusion, our results demonstrate that COL's toxicity to the gut microbiome is compatible with intestinal injuries, inflammatory pathway inhibition, and increased intestinal permeability; our results also represent a novel insight to uncover the adverse reactions of COL in the gastrointestinal tract.


Assuntos
Colchicina/toxicidade , Citocinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo , Animais , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos , Permeabilidade
3.
J Anim Sci ; 98(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877510

RESUMO

The study was conducted to investigate the efficacy of a probiotic Bacillus subtilis strain on growth performance, diarrhea, systemic immunity, and intestinal health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli and to compare the efficacy of B. subtilis with that of carbadox. Weaned pigs (n = 48, 6.17 ± 0.36 kg body weight [BW]) were individually housed in disease containment rooms and randomly allotted to one of four dietary treatments: negative control (NC, control diet without E. coli challenge), positive control (PC, control diet with E. coli challenge), and supplementation of 50 mg/kg of carbadox (antibiotic growth promotor [AGP]) or 2.56 × 109 CFU/kg of B. subtilis probiotics (PRO). The experiment lasted for 28 d with 7 d before and 21 d after the first E. coli inoculation. Fecal and blood samples were collected on days 0, 3, 7, 14, and 21 post inoculation (PI) to analyze ß-hemolytic coliforms and complete blood cell count, respectively. Diarrhea score was recorded daily for each pig to calculate the frequency of diarrhea. All pigs were euthanized at day 21 PI to collect jejunal and ileal mucosa for gene expression analysis. Pigs in AGP had greater (P < 0.05) BW on days 7, 14, and 21 PI than pigs in PC and PRO groups. Supplementation of PRO enhanced pigs' BW on day 21 PI compared with the PC. Escherichia coli F18 challenge reduced (P < 0.05) average daily gain (ADG) and feed efficiency from day 0 to 21 PI, while supplementation of carbadox or PRO enhanced ADG and feed efficiency in E. coli F18-challenged pigs from day 0 to 21 PI. Pigs in AGP and PRO groups had reduced (P < 0.05) frequency of diarrhea throughout the experiment and fecal ß-hemolytic coliforms on day 7 PI than pigs in the PC. Pigs in PRO had greater (P < 0.05) gene expression of CLDN1 in jejunal mucosa than pigs in the PC. Supplementation of carbadox or PRO reduced (P < 0.05) the gene expression of IL6 and PTGS2 in ileal mucosa of E. coli-infected pigs compared with pigs in the PC. Pigs in the PRO group had lower (P < 0.05) white blood cell number and neutrophil count, and serum haptoglobin concentration on day 7 PI, and less (P < 0.05) monocyte count on day 14 PI, compared with PC. In conclusion, supplementation of probiotic B. subtilis could enhance disease resistance and promote the growth performance of weaned pigs under disease challenge conditions. The potential mechanisms include but not limited to enhanced gut barrier integrity and local and systemic immune responses of weaned pigs.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/fisiologia , Carbadox/farmacologia , Diarreia/veterinária , Infecções por Escherichia coli/veterinária , Probióticos/farmacologia , Doenças dos Suínos/microbiologia , Animais , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Dieta/veterinária , Escherichia coli Enterotoxigênica/fisiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Feminino , Íleo/efeitos dos fármacos , Íleo/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Masculino , Distribuição Aleatória , Suínos , Doenças dos Suínos/tratamento farmacológico , Desmame
4.
Med Microbiol Immunol ; 209(6): 693-703, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32995957

RESUMO

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman's rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.


Assuntos
Translocação Bacteriana , Bacteriófagos/isolamento & purificação , Microbioma Gastrointestinal , Mucosa Intestinal/efeitos dos fármacos , Leucemia Mieloide Aguda/sangue , RNA Bacteriano/sangue , RNA Ribossômico 16S/sangue , Viremia/diagnóstico , Adulto , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Proteína C-Reativa/análise , Feminino , Humanos , Mucosa Intestinal/microbiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/virologia , Receptores de Lipopolissacarídeos/sangue , Ativação de Macrófagos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Receptores de Superfície Celular/sangue , Viremia/etiologia
5.
Ecotoxicol Environ Saf ; 204: 111072, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758694

RESUMO

Zearalenone (ZEN) is a mycotoxin that causes serious health problems in humans and animals. However, few studies have focused on the destruction of the intestinal barrier caused by ZEN. In this study, rats were exposed to different dosages of ZEN (0, 0.2, 1.0 and 5.0 mg/kg bw) by gavage for 4 weeks. The results showed that 1.0 and 5.0 mg/kg ZEN impaired gut morphology, induced the inflammatory response, reduced mucin expression, increased intestinal permeability, decreased the expression of TJ proteins and activated the RhoA/ROCK pathway. However, 0.2 mg/kg ZEN had no significant effect on intestinal barrier except for reducing the expression of some TJ proteins and mucins. Moreover, exposure to ZEN led to slight imbalance in microbiota. In conclusion, ZEN exposure resulted in intestinal barrier dysfunction by inducing intestinal microbiota dysbiosis, decreasing the expression of TJ proteins, activating the RhoA/ROCK pathway, and inducing the inflammatory response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Relação Dose-Resposta a Droga , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , Masculino , Mucinas/metabolismo , Permeabilidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
6.
Ecotoxicol Environ Saf ; 204: 111069, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758696

RESUMO

We studied the absorption, cytotoxicity and oxidative stress markers of Paralytic Shellfish Toxins (PST) from three extracts from Alexandrium catenella and A. ostenfeldii, in middle Oncorhynchus mykiss intestine in vitro and ex vivo preparations. We measured glutathione (GSH) content, glutathione-S transferase (GST), glutathione reductase (GR) and catalase (CAT) enzymatic activity, and lipid peroxidation in isolated epithelium exposed to 0.13 and 1.3 µM PST. ROS production and lysosomal membrane stability (as neutral red retention time 50%, NRRT50) were analyzed in isolated enterocytes exposed to PST alone or plus 3 µM of the ABCC transport inhibitor MK571. In addition, the concentration-dependent effects of PST on NRRT50 were assayed in a concentration range from 0 to 1.3 µM PST. We studied the effects of three different PST extracts on the transport rate of the ABCC substrate DNP-SG by isolated epithelium. The extract with highest inhibition capacity was selected for studying polarized DNP-SG transport in everted and non-everted intestinal segments. We registered lower GSH content and GST activity, and higher GR activity, with no significant changes in CAT activity, lipid peroxidation or ROS level. PST exposure decreased NRRT50 in a concentration-depend manner (IC50 = 0.0045 µM), but PST effects were not augmented by addition of MK571. All the three PST extracts inhibited ABCC transport activity, but this inhibition was effective only when the toxins were applied to the apical side of the intestine and DNP-SG transport was measured at the basolateral side. Our results indicate that PST are absorbed by the enterocytes from the intestine lumen. Inside the enterocytes, these toxins decrease GSH content and inhibit the basolateral ABCC transporters affecting the normal functions of the cell. Furthermore, PST produce a strong cytotoxic effect to the enterocytes by damaging the lysosomal membrane, even at low, non-neurotoxic concentrations.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Glutationa/análogos & derivados , Mucosa Intestinal/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Saxitoxina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Dinoflagelados/metabolismo , Enterócitos/efeitos dos fármacos , Enterócitos/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Mucosa Intestinal/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lisossomos/metabolismo , Frutos do Mar
7.
J Anim Sci ; 98(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735667

RESUMO

Eugenol (4-allyl-2-methoxyphenol) is an essential oil component, possessing antimicrobial, anti-inflammatory, and antioxidative properties; however, the effect of eugenol on porcine gut inflammation has not yet been investigated. In this study, an in vitro lipopolysaccharide (LPS)-induced inflammation model in porcine intestinal epithelial cells (IPEC-J2) has been set up. Cells were pretreated with 100 µM (16.42 mg/L) eugenol for 2 h followed by 10 µg/mL LPS stimulation for 6 h. Proinflammatory cytokine secretion; reactive oxygen species; gene expression of proinflammatory cytokines, tight junction proteins, and nutrient transporters; the expression and distribution of zonula occludens-1 (ZO-1); transepithelial electrical resistance (TEER); and cell permeability were measured to investigate the effect of eugenol on inflammatory responses and gut barrier function. The results showed that eugenol pretreatment significantly suppressed the LPS-stimulated interleukin-8 level and the mRNA abundance of tumor necrosis factor-α and restored the LPS-stimulated decrease of the mRNA abundance of tight junction proteins, such as ZO-1 and occludin, and the mRNA abundance of nutrient transporters, such as B0 1 system ASC sodium-dependent neutral amino acid exchanger 2, sodium-dependent glucose transporter 1, excitatory amino acid transporter 1, and peptide transporter 1. In addition, eugenol improved the expression and even redistribution of ZO-1 and tended to increase TEER value and maintained the barrier integrity. In conclusion, a low dose of eugenol attenuated inflammatory responses and enhanced selectively permeable barrier function during LPS-induced inflammation in the IPEC-J2 cell line.


Assuntos
Eugenol/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Doenças dos Suínos/induzido quimicamente , Animais , Contagem de Células/veterinária , Linhagem Celular , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Inflamação/veterinária , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ocludina/metabolismo , Permeabilidade , Suínos , Doenças dos Suínos/metabolismo , Doenças dos Suínos/prevenção & controle , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
8.
Toxicol Lett ; 333: 159-169, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32783910

RESUMO

The intestinal epithelium is the first barrier against food contaminants and is highly sensitive to Fusarium toxins, especially deoxynivalenol (DON) and zearalenone (ZEA). Here, we explored the effects of low doses of DON and/or ZEA in naturally moldy diets on intestinal functions in piglets, including inflammatory responses, epithelial barrier, and microbial composition. Piglets were treated with a control diet (CON), DON diet (1000.6 µg/kg), ZEA diet (269.1 µg/kg), and DON + ZEA diet (1007.5 + 265.4 µg/kg), respectively, for 3 weeks and then switched to the same CON diet for another 2 weeks. In the first period, even the selected low doses of DON or ZEA in the diet resulted in intestinal inflammation, diminish protein expression (claudin-4) and altered gut microbiota populations. Whereas upon switching to the CON diet for another 2 weeks, the deleterious effect of ZEA and DON on IL-1ß and Bifidobacterium population could not be recovered. Additionally, combined DON and ZEA negatively affected body weight gain and feed consumption of piglets, as well as shown synergistic effects on evoking pro-inflammatory cytokines contents (TNF-α, IL-1ß, and IL-6) and perturbing the cecum microbiota profile (E. coli, Lactobacillus, and Bifidobacterium). Collectively, chronic consumption of DON and ZEA contaminated feed or food, even at low doses, can induce intestinal damage and may have consequences for animal and human health.


Assuntos
Ração Animal/microbiologia , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Suínos , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/imunologia , Ceco/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Dieta , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Contaminação de Alimentos/análise , Fusarium/crescimento & desenvolvimento , Fusarium/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Hordeum/microbiologia , Inflamação , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Jejuno/efeitos dos fármacos , Jejuno/imunologia , Jejuno/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Zea mays/microbiologia
9.
Phytomedicine ; 78: 153293, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32777486

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an intricate enteric disease with a rising incidence that is closely related to mucosa-barrier destruction, gut dysbacteriosis, and immune disorders. Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, EMO) is a natural anthraquinone derivative that occurs in many Polygonaceae plants. Its multiple pharmacological effects, including antioxidant, immune-suppressive, and anti-bacteria activities, make it a promising treatment option for UC. However, its poor solubility, extensive absorption, and metabolism in the upper gastrointestinal tract may compromise its anti-colitis effects. PURPOSE: EMO was loaded in a colon-targeted delivery system using multifunctional biomedical materials and the enhanced anti-colitis effect involving mucosa reconstruction was investigated in this study. METHODS: EMO-loaded Poly (DL-lactide-co-glycolide)/EudragitⓇ S100/montmorillonite nanoparticles (EMO/PSM NPs) were prepared by a versatile single-step assembly approach. The colon-specific release behavior was characterized in vitro and in vivo, and the anti-colitis effect was evaluated in dextran sulfate sodium (DSS)-induced acute colitis in mice by weight loss, disease activity index (DAI) score, colon length, histological changes, and colitis biomarkers. The integrity of the intestinal mucosal barrier was evaluated through transwell co-culture model in vitro and serum zonulin-related tight junctions and mucin2 (MUC2) in vivo. RESULTS: EMO/PSM NPs with a desirable hydrodynamic diameter (~ 235 nm) and negative zeta potential (~ -31 mV) could prevent the premature drug release (< 4% in the first 6 h in vitro) in the upper gastrointestinal tract (GIT) and boost retention in the lower GIT and inflamed colon mucosa in vivo. Compared to free EMO-treatment of different doses in UC mice, the NPs could enhance the remedial efficacy of EMO in DAI decline, histological remission, and regulation of colitis indicators, such as myeloperoxidase (MPO), nitric oxide (NO), and glutathione (GSH). The inflammatory factors including induced nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-1ß were suppressed by EMO/PSM NPs at both mRNA and protein levels. The obtained NPs could also promote the regeneration of the mucosal barrier via reduced fluorescein isothiocyanate (FITC)-dextran leakage in the transwell co-culture model and decreased serum zonulin levels, which was demonstrated to be associated with the upregulated tight junctions (TJs)-related proteins (claudin-2, occludin, and zo-1) and MUC2 at mRNA level. Moreover, the NPs could contribute to attenuating the liver injury caused by free EMO under excessive immune inflammation. CONCLUSION: Our results demonstrated that EMO/PSM NPs could specifically release EMO in the diseased colon, and effectively enhance the anti-colitis effects of EMO related to intestinal barrier improvement. It can be considered as a novel potential alternative for oral colon-targeted UC therapy by increasing therapeutic efficacy and reducing side-effects.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Emodina/farmacologia , Nanoestruturas/química , Administração Oral , Animais , Células CACO-2 , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Emodina/administração & dosagem , Emodina/efeitos adversos , Emodina/farmacocinética , Glutationa , Humanos , Concentração de Íons de Hidrogênio , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Mucina-2/genética , Nanoestruturas/administração & dosagem , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ácidos Polimetacrílicos/química , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/genética , Distribuição Tecidual
10.
PLoS One ; 15(8): e0237086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764782

RESUMO

Paramylon is a novel ß-glucan that is stored by Euglena gracilis Z, which is a unicellular photosynthesizing green alga with characteristics of both animals and plants. Recent studies have indicated that paramylon functions as an immunomodulator or a dietary fiber. Currently, chronic kidney disease (CKD) is a global health problem, and there is no effective preventive treatment for CKD progression. However, paramylon may suppress the progression of CKD via the elimination of uremic toxins or modulation of gut microbiota, leading to the alleviation of inflammation. The aim of this study was to evaluate the effect of paramylon in CKD rat model. Eight-week-old male Wistar rats with a 5/6 nephrectomy were given either a normal diet or a diet containing 5% paramylon for 8 weeks. Proteinuria was measured intermittently. Serum and kidney tissues were harvested after sacrifice. We performed a renal molecular and histopathological investigation, serum metabolome analysis, and gut microbiome analysis. The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury in the CKD rat model. Renal fibrosis, tubulointerstitial inflammatory cell infiltration, and proinflammatory cytokine gene expression levels tended to be suppressed with paramylon treatment. Further, paramylon inhibited the accumulation of uremic toxins, including tricarboxylic acid (TCA) cycle-related metabolites and modulated a part of CKD-related gut microbiota in the CKD rat model. In conclusion, we suggest that paramylon mainly inhibited the absorption of non-microbiota-derived uremic solutes, leading to protect renal injury via anti-inflammatory and anti-fibrotic effects. Paramylon may be a novel compound that can act against CKD progression.


Assuntos
Glucanos/farmacologia , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Administração Oral , Animais , Ciclo do Ácido Cítrico/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Euglena gracilis/química , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Glucanos/isolamento & purificação , Glucanos/uso terapêutico , Humanos , Mediadores da Inflamação/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Rim/imunologia , Rim/patologia , Masculino , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , Proteinúria/sangue , Proteinúria/patologia , Ratos , Ratos Wistar , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Toxinas Biológicas/sangue , Toxinas Biológicas/metabolismo
11.
Ecotoxicol Environ Saf ; 203: 111032, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745774

RESUMO

Titanium dioxide nanoparticles (Np-TiO2) have become the common component of sunscreen cosmetic products. Np-TiO2 can affect especially aquatic ecosystems health, including aquatic organisms such as fish. It is therefore necessary to acquire a better understanding of the effect of Np-TiO2 on aquatic organisms. This study evaluated the biological effects of Np-TiO2 on Danio rerio, such as survival rate and weight change and, in particular, the Ti content or retention in the intestine and liver, as well as the activities of catalase and superoxide dismutase enzymes. In addition, the structure of the intestine, kidney, and liver was investigated through histological analysis. Ninety zebrafish were used, randomly divided into three treatment-groups: a control group (fed with food without adding Np-TiO2) and two groups of fish fed with food containing Np-TiO2 exposed for 7 and 14 days. The amount of Ti in the liver and intestine was measured using atomic absorption spectrophotometry coupled to a graphite furnace (GFAAS). Morphological analysis and enzyme catalase and superoxide dismutase assays were likewise performed. Ti was detected in all fish even in control group; probably Ti must have been introduced during production by the fish food industry. Structural changes were detected in fish fed with Np-TiO2 as vacuolization and disruption of the apical cytoplasm of epithelial cells that covered the intestinal villi. Although kidney morphology appeared intact, the lumen of the proximal tubule was enlarged, and the cells of the distal tubule were vacuolated. No morphological changes in the liver were detected; however, superoxide dismutase activity decreased, suggesting that liver changes occurred at the molecular level. Thus, Np-TiO2 causes morphological changes in the intestine, kidney, and liver of zebrafish and biochemical changes in the liver exposed for 7 and 14 days. Although not highly lethal, Np-TiO2 in the food chain can interfere with the morphophysiology of aquatic organisms. Neither mortalities nor body weight losses were recorded among fish in all groups over the duration of the experiment.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Bioacumulação , Catalase , Relação Dose-Resposta a Droga , Ecossistema , Cadeia Alimentar , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Nanopartículas/metabolismo , Distribuição Aleatória , Protetores Solares/química , Titânio/metabolismo , Poluentes Químicos da Água/metabolismo
12.
PLoS Negl Trop Dis ; 14(7): e0008462, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628665

RESUMO

BACKGROUND: Anisakis spp. are nematode parasites found in a wide range of marine organisms. Human beings may accidentally become infected, showing the symptoms of anisakiasis and allergic responses. There has been evidence of increased intestinal permeability in A. simplex-sensitized subjects and that specific IgE titres increase in some allergic patients when fishery products are re-introduced into their diet. The aims of this work were to study the effect of A. simplex crude extract on the intestinal integrity and permeability by using Caco-2 cell monolayer. To analyse the capacity of Ani s 4 allergen to cross the epithelial barrier. METHODOLOGY/PRINCIPAL FINDINGS: Cellular bioenergetics, transepithelial electrical resistance, viability, permeability, reactive oxygen species generation and immunofluorescent staining of tight junction proteins were analysed. A. simplex crude extract compromises the Caco-2 cell monolayer integrity in a dose-dependent manner. This effect is detected at 1 hour of culture and integrity is recovered after 24 hours of culture. The epithelial barrier disruption is accompanied by an increase in paracellular permeability and reactive oxygen species production and by a delocalization of occludin and zonula occludens-1. Finally, Ani s 4, a thermostable and resistant to digestion allergen with cystatin activity, is able to cross the epithelial barrier in Caco-2 monolayer and reach a cumulative mean percentage of 22.7% of total concentration in the basolateral side after 24 hours of culture. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that A. simplex induces an early and reversible alteration of integrity and permeability of Caco-2 cell monolayer and that an underlying mechanism of this effect would involve the oxidative stress and disruption of epithelial tight junctions. Additionally, it has been shown that Ani s 4 allergen is able to cross the epithelial barrier. These findings could explain the increased intestinal permeability observed in Anisakis-sensitized patients, the changes over time in IgE sensitization to A. simplex allergens, and the specific IgE persistence in Anisakis allergy.


Assuntos
Anisakis/química , Mucosa Intestinal/efeitos dos fármacos , Ocludina/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Animais , Células CACO-2 , Sobrevivência Celular , Humanos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo , Consumo de Oxigênio , Transporte Proteico , Espécies Reativas de Oxigênio/metabolismo , Extratos de Tecidos
13.
Nanotoxicology ; 14(7): 985-1007, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32619159

RESUMO

Recent studies reported adverse liver effects and intestinal tumor formation after oral exposure to titanium dioxide (TiO2). Other oral toxicological studies, however, observed no effects on liver and intestine, despite prolonged exposure and/or high doses. In the present assessment, we aimed to better understand whether TiO2 can induce such effects at conditions relevant for humans. Therefore, we focused not only on the clinical and histopathological observations, but also used Adverse Outcome Pathways (AOPs) to consider earlier steps (Key Events). In addition, aiming for a more accurate risk assessment, the available information on organ concentrations of Ti (resulting from exposure to TiO2) from oral animal studies was compared to recently reported concentrations found in human postmortem organs. The overview obtained with the AOP approach indicates that TiO2 can trigger a number of key events in liver and intestine: Reactive Oxygen Species (ROS) generation, induction of oxidative stress and inflammation. TiO2 seems to be able to exert these early effects in animal studies at Ti liver concentrations that are only a factor of 30 and 6 times higher than the median and highest liver concentration found in humans, respectively. This confirms earlier conclusions that adverse effects on the liver in humans as a result of (oral) TiO2 exposure cannot be excluded. Data for comparison with Ti levels in human intestinal tissue, spleen and kidney with effect concentrations were too limited to draw firm conclusions. The Ti levels, though, are similar or higher than those found in liver, suggesting these tissues may be relevant too.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas/toxicidade , Baço/efeitos dos fármacos , Titânio/toxicidade , Administração Oral , Animais , Aditivos Alimentares/química , Aditivos Alimentares/metabolismo , Aditivos Alimentares/toxicidade , Humanos , Inflamação , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Nanopartículas/química , Nanopartículas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Titânio/química , Titânio/metabolismo
14.
Proc Natl Acad Sci U S A ; 117(32): 19168-19177, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32719135

RESUMO

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Clostridiales/química , Peptídeos/química , Peptídeos/farmacologia , Antibacterianos/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Peptídeos/isolamento & purificação
15.
Int J Mol Sci ; 21(14)2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32664543

RESUMO

Recently, the world has been dealing with a devastating global pandemic coronavirus infection, with more than 12 million infected worldwide and over 300,000 deaths as of May 15th 2020, related to a novel coronavirus (2019-nCoV), characterized by a spherical morphology and identified through next-generation sequencing. Although the respiratory tract is the primary portal of entry of SARS-CoV-2, gastrointestinal involvement associated with nausea, vomiting and diarrhoea may also occur. No drug or vaccine has been approved due to the absence of evidence deriving from rigorous clinical trials. Increasing interest has been highlighted on the possible preventative role and adjunct treatment of lactoferrin, glycoprotein of human secretions part of a non-specific defensive system, known to play a crucial role against microbial and viral infections and exerting anti-inflammatory effects on different mucosal surfaces and able to regulate iron metabolism. In this review, analysing lactoferrin properties, we propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration. Lactoferrin could counteract the coronavirus infection and inflammation, acting either as natural barrier of both respiratory and intestinal mucosa or reverting the iron disorders related to the viral colonization.


Assuntos
Infecções por Coronavirus/prevenção & controle , Lactoferrina/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Inflamação , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/virologia , Ferro/metabolismo , Lactoferrina/farmacologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/virologia , Internalização do Vírus/efeitos dos fármacos
16.
J Pharmacol Exp Ther ; 374(3): 420-427, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32546529

RESUMO

Inflammatory bowel diseases are caused by inflammation of the gastrointestinal tract, which may or may not have a specific cause or pathogen. They affect millions of people around the world and there are still few effective treatments. The aim of this work is to investigate the anti-inflammatory effect of the IKK-ß inhibitor LASSBio-1524 and its three analogs, LASSBio-1760, LASSBio-1763, and LASSBio-1764, on mediator production and expression of inflammatory enzymes using experimental animal models of intestinal inflammatory diseases. Colitis was performed using two different models, which mimic Crohn disease (induced by dinitrobenzene acid) and ulcerative colitis (induced by sodium dextran sulfate) in mice. In both models, a therapeutic protocol with a daily dose of 1, 3, or 30 µmol/kg was performed. LASSBio-1524 and its three analogs reduced the secretion of tumor necrosis factor-α, IL-1ß, IL-6, IL-12, and IFN-γ and increased secretion of IL-10, protecting gastrointestinal homeostasis. All compounds reduced macro- and microscopic colonic damage caused by experimental colitis and p38 mitogen-activated protein kinase expression in the colon, as well as leukocytosis and anemia resulting from the disease. Our data may suggest LASSBio-1524 and its analogs (LASSBio-1760, LASSBio-1763, and LASSBio-1764) as promising candidates for new prototypes designed to treat inflammatory bowel diseases. SIGNIFICANCE STATEMENT: Three new N-acylhydrazones were synthetized as analogs of LASSBio-1524. All new substances were evaluated in dextran sulfate- and dinitrobenzene acid-induced colitis, with LASSBio-1760, LASSBio-1762, and LASSBio-1763 presenting a significant effect in both models of colitis without toxic effects. The new substances could be considered as a new prototype for the development of new anti-inflammatory treatments of colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Inflamação/tratamento farmacológico , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
17.
Aliment Pharmacol Ther ; 52(2): 284-291, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506635

RESUMO

BACKGROUND: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. AIM: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease. METHODS: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14 weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC). RESULTS: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P < 0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P < 0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, P < 0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC = 0.91) was greater than faecal calprotectin (AUC = 0.51, P < 0.001). CONCLUSION: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease.


Assuntos
Antirreumáticos/uso terapêutico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Oncostatina M/sangue , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Colonoscopia , Doença de Crohn/patologia , Fezes/química , Feminino , Humanos , Doenças Inflamatórias Intestinais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto Jovem
18.
Mol Immunol ; 124: 61-69, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32534355

RESUMO

OBJECTIVES: Although mycophenolate mofetil-induced (MMF) effectively improves long-term graft survival, the gastrointestinal (GI) side effects due to MMF-induced GI barrier damage limit its use in clinic. Keratinocyte growth factor (KGF) plays a crucial role in the intestinal protection and repair process. This study is designed to investigate the protective effect of KGF on MMF-induced intestinal mucosal barrier disruption and the potential mechanism. METHODS: Thirty adult male C57BL/6 mice were assigned to one of the following groups: the MMF group, the MMF + KGF group, and the control group (n = 10 in each group). Animals in the MMF group received MMF (500 mg/kg) by gavage once daily for 15 consecutive days; animals in the MMF + KGF group received MMF (500 mg/kg) by gavage and KGF (5 mg/kg) by intraperitoneal injection once daily for 15 consecutive days; and control mice were given an equal volume of vehicle during the 15-day experimental period. In each group, intestinal paracellular permeability, histopathological changes and shifts in tight junction (TJ) protein were evaluated; further, proliferation and apoptosis of intestinal epithelial cells (IECs) were assessed, and intraepithelial lymphocytes (IELs) were isolated and analyzed by flow cytometry. RESULTS: MMF caused intestinal mucosal injury, increased intestinal mucosal permeability, and altered expression of TJ protein. Moreover, MMF treatment inhibited IEC proliferation and increased apoptosis. MMF treatment resulted in a lower proportion of γδ+ T cells in IELs (γδ+ IELs). Conversely, concurrent administration of KGF with MMF effectively alleviated MMF-induced intestinal mucosal disruption, inhibited the increase in intestinal permeability, and maintained TJ protein expression. KGF also reversed the MMF-mediated inhibition of proliferation and promotion of apoptosis in IECs. In addition, KGF significantly enhanced the proportion of γδ+ IELs. CONCLUSION: Our findings suggest that MMF induces intestinal epithelial barrier disruption in mice. KGF may play a protective role to ameliorate the disruption and provide a therapeutic intervention for gastrointestinal disorders induced by MMF.


Assuntos
Fator 7 de Crescimento de Fibroblastos/farmacologia , Imunossupressores/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Ácido Micofenólico/toxicidade , Animais , Apoptose/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
19.
PLoS One ; 15(6): e0234076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520965

RESUMO

This study investigated the effects of oral administration of ß-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of ß-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between ß-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of ß-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with ß-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by ß-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of ß-glucan was significantly upregulated and enhanced the immune response. ß-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 ß-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of ß-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , beta-Glucanas/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Administração Oral , Animais , Duodeno/metabolismo , Duodeno/patologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucina-18/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ocludina/genética , Ocludina/metabolismo , Coelhos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Regulação para Cima/efeitos dos fármacos
20.
Arch Biochem Biophys ; 689: 108466, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32590067

RESUMO

Nuclear factor erythroid-derived 2-like 2 (Nrf-2) is transcription factor implicated in the antioxidant response element-mediated induction of endogenous antioxidant enzyme such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase, and NAD(P)H quinone dehydrogenase 1, among which HO-1 is an enzyme catalyzing the degradation of heme.producing biliverdin, ferrous iron, and carbon monoxide. In the stomach, as much as regulating gastric acid secretions, well-coordinated establishment of defense system stands for maintaining gastric integrity. In previous study, author et al. for the first time discovered HO-1 induction was critical in affording faithful gastric defense against various irritants including Helicobacter pylori infection, stress, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. In this review article, we can add the novel evidence that dietary walnut intake can be reliable way to rescue from NSAIDs-induced gastrointestinal damages via the induction of HO-1 transcribed with Nrf-2 through specific inactivation of Keap-1. From molecular exploration to translational animal model of indomethacin-induced gastrointestinal damages, significant induction of HO-1 contributed to rescuing from damages. In addition to HO-1 induction action relevant to walnut, we added the description the general actions of walnut extracts or dietary intake of walnut regarding cytoprotection and why we have focused on to NSAID damages.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Alimento Funcional , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/terapia , Juglans , Animais , Alimento Funcional/análise , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastroenteropatias/patologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Juglans/química , Juglans/metabolismo
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