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1.
Nutrients ; 14(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36501112

RESUMO

Alcohol and drug overdoses cause liver diseases such as cirrhosis, hepatitis, and liver cancer globally. In particular, an overdose of acetaminophen (APAP), which is generally used as an analgesic and antipyretic agent, is a major cause of acute hepatitis, and cases of APAP-induced liver damage are steadily increasing. Potential antioxidants may inhibit the generation of free radicals and prevent drug-induced liver damage. Among plant-derived natural materials, radishes (RJ) and turnips (RG) have anti-inflammatory, anticancer, and antioxidant properties due to the presence of functional ingredients, such as glucosinolate and isothiocyanate. Although various functions have been reported, in vivo studies on the antioxidant activity of radishes are insufficient. Therefore, we aim to evaluate the hepatoprotective effects of RG and RJ in APAP-induced liver-damaged mice. RG and RJ extracts markedly improved the histological status, such as inflammation and infiltration, of mice liver tissue, significantly decreased the levels of alanine transaminase, aspartate aminotransferase, and malondialdehyde, and significantly increased the levels of glutathione, superoxide dismutase and catalase in the APAP-induced liver-damaged mice. In addition, RG and RJ extracts significantly increased the expression of Nrf-2 and HO-1, which are antioxidative-related factors, and regulated the BAX and BCL-2, thereby showing anti-apoptosis activity. These results indicated that RG and RJ extracts protected mice against acute liver injury, attributed to a reduction in both oxidative stress and apoptosis. These findings have clinical implications for the use of RG and RJ extracts as potential natural candidates for developing hepatoprotective agents.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Raphanus , Camundongos , Animais , Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse Oxidativo , Aspartato Aminotransferases/metabolismo , Alanina Transaminase/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fígado/metabolismo , Hepatopatias/metabolismo
2.
Front Endocrinol (Lausanne) ; 13: 1041616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387912

RESUMO

Objective: Recent evidence has revealed that the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) may be closely associated with metabolic syndrome and insulin resistance. However, it is unclear whether the AST/ALT ratio correlates with prediabetes risk. The aim of our study was to examine the association between AST/ALT ratios and the risk of prediabetes among a large cohort of Chinese subjects. Methods: This retrospective cohort study recruited 75204 Chinese adults with normoglycemia at baseline who underwent physical examinations at the Rich Healthcare Group from 2010 to 2016. The AST/ALT ratio at baseline was the target independent variable, and the risk of developing prediabetes during follow-up was the dependent variable. Cox proportional-hazards regression was used to evaluate the independent association between the AST/ALT ratio and prediabetes. This study identified nonlinear relationships by applying a generalized additive model (GAM) and smooth curve fitting. In order to assess the robustness of this study, we performed a series of sensitivity analyses. Moreover, we performed a subgroup analysis to evaluate the consistency of the association in different subgroups. Data from this study have been updated on the DATADRYAD website. Results: The AST/ALT ratio was negatively and independently related to the prediabetes risk among Chinese adults (HR: 0.76, 95% CI: 0.75-0.84, P<0.0001) after adjusting demographic and biochemical covariates. Furthermore, a nonlinear relationship between the AST/ALT ratio and the risk of developing prediabetes was found at an inflection point of 1.50 for the AST/ALT ratio. When the AST/ALT ratio was to the left of the inflection point (AST/ALT ratio ≤ 1.50), the AST/ALT ratio was negatively related to the prediabetes risk (HR:0.70, 95%CI: 0.65-0.76, P<0.0001). In contrast, the relationship tended to be saturated when the AST/ALT ratio was more than 1.50 (HR: 1.01, 95%CI: 0.89-1.15, P=0.8976). Our findings remained robust across a range of sensitivity analyses. Subgroup analysis revealed that other variables did not alter the relationship between the AST/ALT ratio and prediabetes risk. Conclusion: This study revealed that AST/ALT ratio was negatively and independently associated with prediabetes risk among Chinese participants. The relationship between the AST/ALT ratio and prediabetes risk was nonlinear, and AST/ALT ratio ≤ 1.50 was strongly inversely correlated with prediabetes risk.


Assuntos
Estado Pré-Diabético , Adulto , Humanos , Aspartato Aminotransferases/metabolismo , Alanina Transaminase/metabolismo , Estudos Retrospectivos , Estado Pré-Diabético/epidemiologia , China/epidemiologia
3.
Pathol Res Pract ; 240: 154186, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36327814

RESUMO

The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n = 5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.


Assuntos
Água Potável , Camundongos , Animais , Catalase/metabolismo , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Água Potável/metabolismo , Deutério/metabolismo , Deutério/farmacologia , Ácido N-Acetilneuramínico/metabolismo , Ácido N-Acetilneuramínico/farmacologia , Estresse Oxidativo , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Peroxidação de Lipídeos , Antioxidantes/farmacologia , Glutationa/metabolismo , Fígado/patologia , Glutationa Transferase , Oxidantes/metabolismo , Oxidantes/farmacologia , Superóxido Dismutase/metabolismo
4.
Anim Sci J ; 93(1): e13772, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36289593

RESUMO

The effects of long-term feeding of wood kraft pulp (KP) silage containing sweet-potato shochu distillery by-product (SDP) on feed intake, feed digestibility, rumen fermentation, and growth performance of Japanese Black steers were investigated during the early fattening period. Ten Japanese Black steers (9.8 ± 0.6 months of age) were used in this study. Five steers (KP group) were fed KP silage as a replacement for 10% timothy hay (dry matter bases), in contrast to the other five (control group). KP silage consisted of 92.9% KP and 7.1% SDP (dry matter bases). The experiment was conducted for 18 weeks. No significant differences were observed in terms of feed intake, feed digestibility, or daily body weight gain between the groups. In addition, diurnal changes in the rumen pH and ruminal lipopolysaccharide activity did not differ between the groups. However, the plasma concentration of aspartate transaminase in the KP group was slightly lower (P = 0.078) than that in the control group. Thus, our study suggested that feeding KP silage does not reduce feed intake or affect the rumen fermentation or growth performance of Japanese Black fattening steer.


Assuntos
Ipomoea batatas , Solanum tuberosum , Animais , Silagem , Fermentação , Rúmen/metabolismo , Digestão , Madeira , Lipopolissacarídeos/metabolismo , Dieta/veterinária , Ingestão de Alimentos , Aspartato Aminotransferases/metabolismo , Ração Animal/análise
5.
Nutrients ; 14(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36296994

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum condition characterized by excessive liver fat accumulation in people who do not abuse alcohol. There is no effective medical treatment for NAFLD; therefore, most important recommendations to reduce liver steatosis are diet and lifestyle, including proper physical activity. The aim of our study was to analyze the fatty acids and eicosanoids changes in the serum of patients who consumed high-fiber rolls for 8 weeks. MATERIALS AND METHODS: The group of 28 Caucasian participants was randomly divided into two groups, those who received 24 g of fiber/day-from 2 buns of 12 g each (n = 14), and those who received 12 g of fiber/day-from 2 buns of 6 g (n = 14). At the beginning and on the last visit of the 8-week intervention, all patients underwent NAFLD evaluation, biochemical parameter measurements, and fatty acids and eicosanoids evaluation. RESULTS: Patients who received 12 g of fiber had significantly reduced liver steatosis and body mass index. In the group who received 24 g of fiber/day, we observed a trend to liver steatosis reduction (p = 0.07) and significant decrease in aspartate aminotransferase (p = 0.03) and total cholesterol (p = 0.03). All changes in fatty acid and eicosanoids profile were similar. Fatty acids analysis revealed that extra fiber intake was associated with a significant increase in monounsaturated fatty acids and decrease in saturated fatty acids. Moreover, both groups showed increased concentration of gamma linoleic acid and docosahexaenoic acid. We also observed reduction in prostaglandin E2. CONCLUSIONS: Our study revealed that a high amount of fiber in the diet is associated with a reduction in fatty liver, although this effect was more pronounced in patients in the lower fiber group. However, regardless of the amount of fiber consumed, we observed significant changes in the profile of FAs, which may reflect the positive changes in the lipids liver metabolism. Regardless of the amount of fiber consumed, patients decreased the amount of PGE2, which may indicate the lack of disease progression associated with the development of inflammation.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácidos Graxos/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Fígado/metabolismo , Dieta , Aspartato Aminotransferases/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Fibras na Dieta/metabolismo , Eicosanoides/metabolismo , Ácidos Linoleicos/metabolismo , Prostaglandinas E/metabolismo , Prostaglandinas/metabolismo , Colesterol/metabolismo
6.
Chemosphere ; 309(Pt 1): 136637, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36181844

RESUMO

Zearalenone is a mycotoxin produced by several species of Fusarium fungi, which contaminates crop and cereal products worldwide. It is widely distributed and can be transported from agricultural fields to the aquatic environment via soil run-off. Zearalenone exposure can cause serious health problems to humans and animals, including estrogenic, immunotoxic, and xenogenic effects. Though its hepatotoxicity has been reported by few studies, the underlying mechanisms are yet to be investigated. This study aimed to comprehensively evaluate the hepatotoxic effects of zearalenone and its molecular mechanism in the zebrafish model system. First, we found zearalenone exposure can cause liver injury, as evidenced by reduced liver size, decreased liver-specific fluorescence, increased aspartate aminotransferase (AST) activity, delayed yolk sac absorption and lipid accumulation. Then, RNA sequencing (RNA-seq) was performed using dissected zebrafish fry liver, which found genes involved in oxidation and reduction were significantly enriched. Quantitative real-time PCR further confirmed the dysregulated expression of several antioxidant enzymes. Additionally, lipid peroxidation was proved by increased malondialdehyde (MDA) production and gene expression at the mRNA level. In contrast to the previous study, apoptosis was likely decreased in response to zearalenone exposure. Last, glucuronidation and amino acid metabolism were also disrupted by zearalenone. Our results revealed the complex mechanism of zearalenone-induced hepatotoxicity, which is a valuable contribution to a more comprehensive understanding of the toxicity of zearalenone.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Micotoxinas , Zearalenona , Animais , Aminoácidos , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Lipídeos , Malondialdeído , Micotoxinas/toxicidade , RNA Mensageiro , Solo , Transcriptoma , Zearalenona/toxicidade , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
7.
Aquat Toxicol ; 252: 106322, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36240591

RESUMO

Cyhalofop­butyl is a highly effective aryloxyphenoxypropionate herbicide and widely used for weed control in paddy fields. With the increasing residue of cyhalofop­butyl, it poses a threat to the survival of aquatic organisms. Here, we investigated the effect of cyhalofop­butyl on zebrafish to explore its potential hepatotoxic mechanism. The results showed that cyhalofop­butyl induced hepatocyte degeneration, vacuolation and necrosis of larvae after embryonic exposure for 4 days and caused liver atrophy after 5 days. Meanwhile, the activities of enzymes related to liver function were significantly increased by 0.2 mg/L cyhalofop­butyl and higher, such as alanine transaminase (ALT) and aspartate transaminase (AST). And the contents of triglyceride (TG) involved in lipid metabolism were significantly decreased by 0.4 mg/L cyhalofop-buty. The expression of genes related to liver development was also significantly down-regulated. Furthermore, transcriptome results showed that the pathways involved in metabolism, immune system and endocrine system were significantly impacted, which may be related to hepatoxicity. To sum up, the present study demonstrated the hepatoxicity caused by cyhalofop-buty and its underlying mechanism. The results may provide new insights for the risk of cyhalofop­butyl to aquatic organisms and new horizons for the pathogenesis of hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Herbicidas , Poluentes Químicos da Água , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Alanina Transaminase/metabolismo , Poluentes Químicos da Água/toxicidade , Aspartato Aminotransferases/metabolismo , Herbicidas/toxicidade , Herbicidas/metabolismo , Triglicerídeos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Perfilação da Expressão Gênica , Fígado
8.
Front Immunol ; 13: 988668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268033

RESUMO

Background: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are the two most common subtypes of liver failure. They are both life-threatening clinical problems with high short-term mortality. Although liver transplantation is an effective therapeutic, its application is limited due to the shortage of donor organs. Given that both ACLF and ALF are driven by excessive inflammation in the initial stage, molecules targeting inflammation may benefit the two conditions. MicroRNAs (miRNAs) are a group of small endogenous noncoding interfering RNA molecules. Regulation of miRNAs related to inflammation may serve as promising interventions for the treatment of liver failure. Aims: To explore the role and mechanism of miR-125b-5p in the development of liver failure. Methods: Six human liver tissues were categorized into HBV-non-ACLF and HBV-ACLF groups. Differentially expressed miRNAs (DE-miRNAs) were screened and identified through high-throughput sequencing analysis. Among these DE-miRNAs, miR-125b-5p was selected for further study of its role and mechanism in lipopolysaccharide (LPS)/D-galactosamine (D-GalN) -challenged Huh7 cells and mice in vitro and in vivo. Results: A total of 75 DE-miRNAs were obtained. Of these DE-miRNAs, miR-125b-5p was the focus of further investigation based on our previous findings and preliminary results. We preliminarily observed that the levels of miR-125b-5p were lower in the HBV-ACLF group than in the HBV-non-ACLF group. Meanwhile, LPS/D-GalN-challenged mice and Huh7 cells both showed decreased miR-125b-5p levels when compared to their untreated control group, suggesting that miR-125b-5p may have a protective role against liver injury, regardless of ACLF or ALF. Subsequent results revealed that miR-125b-5p not only inhibited Huh7 cell apoptosis in vitro but also relieved mouse ALF in vivo with evidence of improved liver histology, decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reduced tumor necrosis factor-α (TNF-α) and IL-1ß levels. Based on the results of a biological prediction website, microRNA.org, Kelch-like ECH-associated protein 1 (Keap1) was predicted to be one of the target genes of miR-125b-5p, which was verified by a dual-luciferase reporter gene assay. Western blot results in vitro and in vivo showed that miR-125b-5p could decrease the expression of Keap1 and cleaved caspase-3 while upregulating the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1(HO-1). Conclusion: Upregulation of miR-125b-5p can alleviate acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway, and regulation of miR-125b-5p may serve as an alternative intervention for liver failure.


Assuntos
Insuficiência Hepática Crônica Agudizada , MicroRNAs , Animais , Humanos , Camundongos , Insuficiência Hepática Crônica Agudizada/genética , Insuficiência Hepática Crônica Agudizada/terapia , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Caspase 3/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Galactosamina , Heme Oxigenase-1/metabolismo , Inflamação , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
9.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 57(10): 1048-1056, 2022 Oct 09.
Artigo em Chinês | MEDLINE | ID: mdl-36266079

RESUMO

Objective: Brain and muscle ARNT-like protein 1 (BMAL1) is a core component of hepatocyte molecular clock and plays an important role in the regulation of other related rhythmic genes in the body through a transcriptional-translational feedback loop in molecular circadian oscillations. Therefore, the aim of this study was to investigate the role of BMAL1 in the rat periodontitis-induced liver injury. Methods: Twelve male Wistar rats were divided into the control group and the periodontitis group according to the random number table method. The rats in the control group were untreated. The periodontitis models were established by ligating the necks of the bilateral maxillary first molars in the periodontitis group rats. After 8 weeks, periodontal clinical indexes of rats in both groups were examined and executed. Micro-CT scans of the maxilla were performed and levels of the alveolar bone resorption were analyzed. Pathological changes in periodontal and liver tissue of rats in two groups were detected by HE and oil red O staining. Biochemical kits were used to detect glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), total cholesterol (TC) and triglycerides (TG) in serum. The gene and protein expression levels of BMAL1, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) in liver tissue were measured by real time fluorescent quantitative-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) assays. Apoptosis was detected in liver tissues by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) kit staining. Results: The results of HE staining of maxillary first molars and micro-CT results of maxillary bones showed that alveolar bone resorption was significant in the periodontitis group of rats. The liver histopathology results showed infiltrated inflammatory cells in the liver tissue, disorganized liver cords and a large number of lipid droplets formed in the hepatocytes of the periodontitis group compared with the control group. The results of serum biochemical assay showed that the levels of GOT [(62.77±2.59) U/L], GPT [(47.54±1.04) U/L], TC [(3.19±0.23) mmol/L] and TG [(1.11±0.09) mmol/L] in the serum of rats with periodontitis were significantly higher than that in the control group respectively [GOT: (38.66±2.47) U/L, GPT: (31.48±1.57) U/L, TC: (1.60±0.05) mmol/L and TG: (0.61±0.09) mmol/L](P=0.003, P=0.001, P=0.002, P=0.038). qRT-PCR results showed that the mRNA expression level of BMAL1 was significantly decreased in liver tissue of the periodontitis group [(0.60±0.04)%] compared to the control group [(1.01±0.07)%] (t=4.80, P=0.009), while the mRNA expression levels of NF-κB and TNF-α [(1.62±0.12)%, (2.69±0.16)%] were significantly increased compared to the control group [(1.00±0.03)%, (1.03±0.16)%] (P=0.008, P=0.002); IHC results showed that the protein expression level of BMAL1 in liver tissue of the periodontitis group (averaged optical density, AOD) (11.58±2.15) was down-regulated compared to the control group (AOD) (22.66±1.67) (P=0.015), while NF-κB and TNF-α (AOD) (31.77±2.69, 24.31±2.32) were up-regulated compared to the control group (AOD) (19.40±1.82, 11.92±0.94) (P=0.019, P=0.008). WB results showed that the protein expression level of BMAL1 in liver tissue was down-regulated in the periodontitis group [(0.63±0.10)%] compared to the control group [(1.00±0.06)%] (t=3.19, P=0.033), while NF-κB and TNF-α [(1.61±0.12)%, (2.82±0.23)%] were up-regulated compared to the control group [(1.00±0.12)%, (1.00±0.11)%] (P=0.022, P=0.002). TUNEL staining showed increased apoptotic cells in the liver tissue of the periodontitis group of rats compared to the control group. Conclusions: Periodontitis may induce liver injury by down-regulating the BMAL1 expression levels in liver tissue, which in turn activates NF-κB signaling molecules, leading to the elevated levels of inflammation and apoptosis in rat liver.


Assuntos
Reabsorção Óssea , Doença Hepática Crônica Induzida por Substâncias e Drogas , Periodontite , Animais , Masculino , Ratos , Alanina Transaminase/metabolismo , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Aspartato Aminotransferases/metabolismo , Biotina/metabolismo , Encéfalo , Colesterol , DNA Nucleotidilexotransferase/metabolismo , Músculos/metabolismo , NF-kappa B/metabolismo , Ratos Wistar , RNA Mensageiro/metabolismo , Triglicerídeos , Fator de Necrose Tumoral alfa/metabolismo
10.
Biomed Pharmacother ; 156: 113840, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36252356

RESUMO

Cordia rothii Roem. & Schult. possesses various beneficial effects and is traditionally used in folk medicine against liver diseases but its molecular mechanism remains unclear. Antioxidant and hepatoprotective effects of Cordia rothii methanolic fraction (CRMF) were investigated in CCl4-induced liver injury. Antioxidant effects were evaluated using DPPH assay, ferric thiocyanate (FTC) assay, and HepG2 cells. A qualitative analysis of phytochemicals was carried out by gas chromatography-mass spectrometry (GC-MS). The hepatoprotective effects of CRMF were assessed against CCl4-induced liver damage in rats. Our results showed that CRMF significantly increased cell viability against CCl4-induced HepG2 cells. The in vivo results showed that CRMF significantly reduced the level of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, hepatic antioxidant enzymes, including superoxide dismutase, malondialdehyde, and increased glutathione level. Normal hepatocyte integrity and microstructures were observed in histopathological results. Furthermore, the mRNA level of inflammatory mediators including interleukon (IL)-1ß, IL-6, TNF-α, nuclear factor kappa B (NF-KB), IL-10 and nuclear factor-erythroid factor 2-related factor 2 (NrF2) were reverted in CRMF pretreatment groups. Thus, CRMF exhibited strong antioxidant, and hepatoprotective activities, which may involve Nrf2-NFκB pathways.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Cordia , Ratos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Tetracloreto de Carbono/toxicidade , Antioxidantes/farmacologia , Antioxidantes/metabolismo , NF-kappa B/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse Oxidativo , Fígado , Aspartato Aminotransferases/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo
11.
Int J Mol Sci ; 23(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36233086

RESUMO

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.


Assuntos
Antipiréticos , Doença Hepática Induzida por Substâncias e Drogas , Receptor Nuclear Órfão DAX-1 , Fator 2 Relacionado a NF-E2 , Acetaminofen/toxicidade , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Proteínas Correpressoras/metabolismo , Receptor Nuclear Órfão DAX-1/genética , Glutationa/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Receptores Nucleares Órfãos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
12.
Phytomedicine ; 107: 154484, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36215787

RESUMO

BACKGROUND: Translocator protein (TSPO) is an 18-kDa transmembrane protein found primarily in the mitochondrial outer membrane, and it is implicated in inflammatory responses, such as cytokine release. Koumine (KM) is an indole alkaloid extracted from Gelsemium elegans Benth. It has been reported to be a high-affinity ligand of TSPO and to exert anti-inflammatory and immunomodulatory effects in our recent studies. However, the protective effect of KM on sepsis-associated liver injury (SALI) and its mechanisms are unknown. PURPOSE: To explore the role of TSPO in SALI and then further explore the protective effect and mechanism of KM on SALI. METHODS: The effect of KM on the survival rate of septic mice was confirmed in mouse models of caecal ligation and puncture (CLP)-induced and lipopolysaccharide (LPS)-induced sepsis. The protective effect of KM on CLP-induced SALI was comprehensively evaluated by observing the morphology of the mouse liver and measuring liver injury markers. The serum cytokine content was detected in mice by flow cytometry. Macrophage polarization in the liver was examined using western blotting. TSPO knockout mice were used to explore the role of TSPO in sepsis liver injury and verify the protective effect of KM on sepsis liver injury through TSPO. RESULTS: KM significantly improved the survival rate of both LPS- and CLP-induced sepsis in mice. KM has a significant liver protective effect on CLP-induced sepsis in mice. KM treatment ameliorated liver ischaemia, improved liver pathological injuries, and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and proinflammatory cytokines in serum. Western blotting results showed that KM inhibited M1 polarization of macrophages and promoted M2 polarization. In TSPO knockout mice, we found that TSPO knockout can improve the survival rate of septic mice, ameliorate liver ischaemia, improve liver pathological injuries, and decrease the levels of ALT, AST, and LDH. In addition, TSPO knockout inhibits the M1 polarization of macrophages in the liver of septic mice and promotes M2 polarization and the serum levels of proinflammatory cytokines. Interestingly, in TSPO knockout septic mice, these protective effects of KM were no longer effective. CONCLUSIONS: We report for the first time that TSPO plays a critical role in sepsis-associated liver injury by regulating the polarization of liver macrophages and reducing the inflammatory response. KM, a TSPO ligand, is a potentially desirable candidate for the treatment of SALI that may regulate macrophage M1/M2 polarization through TSPO in the liver.


Assuntos
Lipopolissacarídeos , Sepse , Alanina Transaminase/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Aspartato Aminotransferases/metabolismo , Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Alcaloides Indólicos/farmacologia , Lactato Desidrogenases/metabolismo , Ligantes , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Macrófagos , Camundongos , Camundongos Knockout , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo
13.
Drug Des Devel Ther ; 16: 3327-3342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199629

RESUMO

Aim: Liver regulates metabolism of biomolecules and injury of liver causes distortion of metabolic functions. This injury may be oxidative or inflammatory induced by numerous factors including alcohol, pathogens and xenobiotics. This scientific study was planned to investigate the anti-inflammatory and anti-oxidant potential of p-coumaric acid (p-CA) on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN) induced liver injury. Methods: DPPH analysis, reducing power assay and HPLC analysis were performed during in-vitro studies of p-CA. Similarly, in-vivo experiments were performed using Wistar Albino rats. Normal control and intoxicated group received (5mL/kg normal saline p.o), standard treatment groups received ascorbic acid (100mg/kg p.o) and silymarin (25mg/kg p.o), while p-CA treatment groups received (100mg/kg p.o) for 28-days. After completion of 28-days, LPS/D-GalN injection (300 mg D-GalN/kg and 10 µg LPS/kg i.p.) was given at 6th, 12th and 24-hours to all groups except normal control group. Animals were sacrificed; serum and liver samples were harvested and subjected to biochemical and histological examinations, respectively. Results: The results revealed that p-CA possess strong antioxidant activity. Increased levels of leukocyte infiltration (TLC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), lipid panel (eg TG, TC, LDL-C, VLDL-C), whereas decreased HDL-C levels noticed in LPS/D-GalN groups as compared to normal control groups. Pro-Inflammatory markers (eg TNF-α, IL-6, IL-1ß) and lipid peroxidation marker, eg malondialdehyde (MDA) increased while superoxide dismutase (SOD) and reduced glutathione (GSH) levels were decreased significantly in groups treated with LPS/D-GalN. ANOVA with Bonferroni post hoc analysis was used for statistical analysis of. H&E staining was done to assess architectural abnormalities among liver cells. Conclusion: In conclusion, p-CA could ameliorate LPS/D-GalN induced hepatic injury via regulation of immune responses, liver function enzymes, lipid profile, oxidative stress and pro-inflammatory markers.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Silimarina , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Aspartato Aminotransferases/metabolismo , Bilirrubina , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , LDL-Colesterol , Ácidos Cumáricos , Galactosamina/farmacologia , Glutationa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Fígado , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Solução Salina/farmacologia , Silimarina/farmacologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Cancer Discov ; 12(10): 2237-2239, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36196574

RESUMO

In this issue, Abrego and colleagues describe an unexpected role for the mitochondrial enzyme glutamic-oxaloacetic transaminase (GOT2) in pancreatic cancer, whereby it acts as a nuclear fatty acid transporter binding to and activating the PPARδ nuclear receptor. In turn, the GOT2-PPARδaxis drives immunosuppression by suppressing T cell-mediated antitumor immunity. See related article by Abrego et al., p. 2414 (3).


Assuntos
PPAR delta , Neoplasias Pancreáticas , Aspartato Aminotransferase Mitocondrial/metabolismo , Aspartato Aminotransferases/metabolismo , Ácidos Graxos , Humanos , Terapia de Imunossupressão , Neoplasias Pancreáticas/patologia
15.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36292919

RESUMO

Jatrorrhizine (JAT) is one of the major bioactive protoberberine alkaloids found in rhizoma coptidis, which has hypoglycemic and hypolipidemic potential. This study aimed to evaluate the vasoprotective effects of JAT in diabetes and obesity and the underlying mechanism involved. Mouse aortas, carotid arteries and human umbilical cord vein endothelial cells (HUVECs) were treated with risk factors (high glucose or tunicamycin) with and without JAT ex vivo and in vitro. Furthermore, aortas were obtained from mice with chronic treatment: (1) control; (2) diet-induced obese (DIO) mice fed a high-fat diet (45% kcal% fat) for 15 weeks; and (3) DIO mice orally administered JAT at 50 mg/kg/day for the last 5 weeks. High glucose or endoplasmic reticulum (ER) stress inducer tunicamycin impaired acetylcholine-induced endothelium-dependent relaxations (EDRs) in mouse aortas, induced oxidative stress in carotid arteries and HUVECs, downregulated phosphorylations of Akt at Ser473 and eNOS at Ser1177 and enhanced ER stress in mouse aortas and HUVECs, and these impairments were reversed by cotreatment with JAT. JAT increased NO release in high-glucose-treated mouse aortas and HUVECs. In addition, chronic JAT treatment restored endothelial function with EDRs comparable to the control, increased Akt/eNOS phosphorylation, and attenuated ER stress and oxidative stress in aortas from DIO mice. Blood pressure, glucose sensitivity, fatty liver and its morphological change, as well as plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and plasma lipid profile, were also normalized by JAT treatment. Collectively, our data may be the first to reveal the vasoprotective effect of JAT that ameliorates endothelial dysfunction in diabetes and obesity through enhancement of the Akt/eNOS pathway and NO bioavailability, as well as suppression of ER stress and oxidative stress.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas , Camundongos , Humanos , Animais , Estresse do Retículo Endoplasmático , Tunicamicina/farmacologia , Endotélio Vascular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Acetilcolina/metabolismo , Alanina Transaminase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Camundongos Endogâmicos C57BL , Diabetes Mellitus/metabolismo , Estresse Oxidativo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Obesidade/metabolismo , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Aspartato Aminotransferases/metabolismo , Lipídeos/farmacologia
16.
Nutr Res ; 106: 101-118, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36183668

RESUMO

Previously, our group found that the dietary trace mineral element selenium and vitamin B6 (VitB6) alone was involved in lipid metabolism. However, the effects of selenium combined with VitB6 on hyperlipidemia and lipid metabolism have not been reported until now. We hypothesized that selenium and VitB6 cosupplementation would alleviate the hyperlipidemic and hepatic dysfunction and with minimum side effects in a Sprague-Dawley rat model of hyperlipidemia induced by a high-fat diet. Our results showed that selenium combined with VitB6 could improve dyslipidemia and displayed better in vivo hypocholesterolemic abilities at early intervention. Moreover, cosupplementation reduced atherogenic indexes (atherogenic index and atherogenic index of plasm) and the ratio of ApoB/ApoA1. The liver function index aspartate aminotransferase in serum was reduced, as was and total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in liver. The intervention also increased the levels of ApoA1 in serum and high-density lipoprotein cholesterol of liver. In addition, the combination of selenium and VitB6 decreased liver lipid deposition and alleviated steatosis, reduced adipocyte size of white adipose tissue, increased the activities of hepatic lipase and total lipase and the hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) level, decreased the hepatic mRNA transcription of lipogenic and regulatory genes including Srebf1 and downstream fat synthesis-related enzymes (Acc and Fasn) and cholesterol synthesis speed limiting enzyme Hmgr, increased the mRNA abundance of Lcat and Cyp7a1, increased the protein expression of SIRT1 and PPARα, and up-regulated the protein expression of sterol regulatory element-binding protein 1c in the livers of hyperlipidemia rats. We first demonstrated that oral selenium and VitB6 cosupplementation exerted synergism in lowering blood and liver lipid profiles and antiatherosclerotic effects in hyperlipidemic rats by reducing endogenous cholesterol and lipid synthesis, enhancing the transport of cholesterol to hepatocytes and promoting fatty acid beta oxidation.


Assuntos
Fígado Gorduroso , Hiperlipidemias , Selênio , Oligoelementos , Animais , Apolipoproteínas B , Aspartato Aminotransferases/metabolismo , Colesterol/metabolismo , HDL-Colesterol , LDL-Colesterol/metabolismo , Coenzima A/metabolismo , Coenzima A/farmacologia , Coenzima A/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Fígado Gorduroso/metabolismo , Hiperlipidemias/tratamento farmacológico , Lipase/metabolismo , Lipase/farmacologia , Lipase/uso terapêutico , Metabolismo dos Lipídeos , Fígado/metabolismo , Oxirredutases/metabolismo , Oxirredutases/farmacologia , Oxirredutases/uso terapêutico , PPAR alfa/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Selênio/farmacologia , Selênio/uso terapêutico , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Oligoelementos/farmacologia , Oligoelementos/uso terapêutico , Triglicerídeos/metabolismo , Vitamina B 6 , Vitaminas/farmacologia
17.
J Transl Med ; 20(1): 479, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266691

RESUMO

BACKGROUND: Explanted livers from patients with inherited metabolic liver diseases possess the potential to be a cell source of good-quality hepatocytes for hepatocyte transplantation (HT). This study evaluated the therapeutic effects of domino HT using hepatocytes isolated from explanted human livers for acute liver failure (ALF). METHODS: Isolated hepatocytes were evaluated for viability and function and then transplanted into D-galactosamine/lipopolysaccharide-induced ALF mice via splenic injection. The survival rate was analyzed by the Kaplan-Meier method and log-rank test. Liver function was evaluated by serum biochemical parameters, and inflammatory cytokine levels were measured by ELISA. The pathological changes in the liver tissues were assessed by hematoxylin-eosin staining. Hepatocyte apoptosis was investigated by TUNEL, and hepatocyte apoptosis-related proteins were detected by western blot. The localization of human hepatocytes in the injured mouse livers was detected by immunohistochemical analyses. RESULTS: Hepatocytes were successfully isolated from explanted livers of 10 pediatric patients with various liver-based metabolic disorders, with an average viability of 85.3% ± 13.0% and average yield of 9.2 × 106 ± 3.4 × 106 cells/g. Isolated hepatocytes had an excellent ability to secret albumin, produce urea, uptake indocyanine green, storage glycogen, and express alpha 1 antitrypsin, albumin, cytokeratin 18, and CYP3A4. Domino HT significantly reduced mortality, decreased serum levels of alanine aminotransferase and aspartate aminotransferase, and improved the pathological damage. Moreover, transplanted hepatocytes inhibited interleukin-6 and tumor necrosis factor-α levels. Domino HT also ameliorates hepatocyte apoptosis, as evidenced by decreased TUNEL positive cells. Positive staining for human albumin suggested the localization of human hepatocytes in ALF mice livers. CONCLUSION: Explanted livers from patients with inheritable metabolic disorders can serve as a viable cell source for cell-based therapies. Domino HT using hepatocytes with certain metabolic defects has the potential to be a novel therapeutic strategy for ALF.


Assuntos
Hepatócitos , Falência Hepática Aguda , Doenças Metabólicas , Animais , Criança , Humanos , Camundongos , Alanina Transaminase/metabolismo , Albuminas/metabolismo , alfa 1-Antitripsina/metabolismo , Aspartato Aminotransferases/metabolismo , Citocromo P-450 CYP3A/metabolismo , Galactosamina/efeitos adversos , Glicogênio/metabolismo , Interleucina-6/metabolismo , Queratina-18/metabolismo , Lipopolissacarídeos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/cirurgia , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/cirurgia , Albumina Sérica Humana/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ureia/metabolismo , Hepatócitos/transplante
18.
J Int Soc Sports Nutr ; 19(1): 623-637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36250147

RESUMO

Background: The purpose of this study is to explore the effect of carbohydrate only or carbohydrate plus protein supplementation on endurance capacity and muscle damage. Methods: Ten recreationally active male runners (VO2max: 53.61 ± 3.86 ml/kg·min) completed run-to-exhaustion test three times with different intakes of intervention drinks. There was a 7-day wash-out period between tests. Each test started with 60 minutes of running at 70% VO2max (phase 1), followed by an endurance capacity test: time-to-exhaustion running at 80% VO2max (phase 2). Participants randomly ingested either 1) 0.4 g/kg BM carbohydrate before phase 1 and before phase 2 (CHO+CHO), 2) 0.4 g/kg BM protein before phase 1 and 0.4 g/kg BM carbohydrate before phase 2 (PRO+CHO), or 3) 0.4 g/kg BM carbohydrate before phase 1 and 0.4 g/kg BM protein before phase 2 (CHO+PRO). All subjects ingested carbohydrate (CHO) 1.2 g/kg BM during phase 1, and blood samples were obtained before, immediately, and 24 h after exercise for measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and myoglobin (MB). Results: There was no significant difference in time to exhaustion between the three supplement strategies (CHO+CHO: 432 ± 225 s; PRO+CHO: 463 ± 227 s; CHO+PRO: 461 ± 248 s). However, ALT and AST were significantly lower in PRO+CHO than in CHO+CHO 24 h after exercise (ALT: 16.80 ± 6.31 vs. 24.39 ± 2.54 U/L; AST: 24.06 ± 4.77 vs. 31.51 ± 7.53 U/L, p < 0.05). MB was significantly lower in PRO+CHO and CHO+PRO than in CHO+CHO 24 h after exercise (40.7 ± 15.2; 38.1 ± 14.3; 64.3 ± 28.9 ng/mL, respectively, p < 0.05). CK increased less in PRO+CHO compared to CHO+CHO 24 h after exercise (404.22 ± 75.31 VS. 642.33 ± 68.57 U/L, p < 0.05). Conclusion: Carbohydrate and protein supplement strategies can reduce muscle damage caused by endurance exercise, but they do not improve endurance exercise capacity.


Assuntos
Carboidratos da Dieta , Resistência Física , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Creatina Quinase , Estudos Cross-Over , Proteínas na Dieta , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético , Mioglobina
19.
Sci Rep ; 12(1): 17410, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36258024

RESUMO

The fish immune system is a topic or subject that offers a unique understanding of defensive system evolution in vertebrate heredity. While gut microbiota plays several roles in fish: well-being, promoting health and growth, resistance to bacterial invasion, regulation of energy absorption, and lipid metabolism. However, studies on fish gut microbiota face practical challenges due to the large number of fish varieties, fluctuating environmental conditions, and differences in feeding habits. This study was carried out to evaluate the impacts of supplemented three autochthonous strains, Bacillus sp. RCS1, Pantoea agglomerans RCS2, and Bacillus cereus RCS3 mixture diet on cobia fish (Rachycentron canadum). Also, chromatography, mass spectrometry and high throughput sequencing were combined to explore composition and metabolite profile of gut microbiota in juvenile cobia fed with supplemented diet. In the trial group, juvenile cobia received diets supplemented with 1 × 1012 CFU mL-1 autochthonous strains for ten weeks and a control diet without supplementation. Juvenile cobia receiving diets supplementation exhibited significantly improved growth than those without additives (control). Haematological indices, such as red blood cells, white blood cells, corpuscular haemoglobin concentration, mean corpuscular volume, haemoglobin, and mean corpuscular haemoglobin, were higher in the supplemented group. Similarly, digestive enzymes (trypsin, lipase, amylase, pepsin and cellulose, activities) activities were higher in supplemented diet with an indigenous isolates mixture. Serum biochemical parameters albumin, globulin, and total protein were significantly higher, while triglyceride, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and cholesterol showed no significant difference. On the other hand, glucose was significantly (P < 0.05) higher in the group without supplementation. On gene expression in the midgut, Immunoglobulin, Colony-stimulating factor receptor 1, major histocompatibility complex 1 were up-regulated by native isolates while T cell receptor beta, and Major histocompatibility complex 2 showed no significant difference. Gut bacterial composition was altered in fish receiving supplemented diet with autochthonous strains. Metabolomics also revealed that some metabolic pathways were considerably enriched in fish fed with supplemented diet; pathway analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed that differentially expressed metabolites were involved in galactose metabolism, tryptophan metabolism, carbohydrate digestion and absorption, purine metabolism, and ABC transporters. Functional analysis of bacterial community showed that differences in enriched metabolic pathways generally comprised carbohydrate and its metabolites, nucleotide and its metabolites, amino acid and its metabolites, heterocyclic compounds, and tryptamines, cholines, pigments. The current investigation results showed that autochthonous strains mixture has significantly enhanced the growth, survival, and innate and adaptive immunities of juvenile cobia.


Assuntos
Microbioma Gastrointestinal , Perciformes , Animais , Alanina/metabolismo , Albuminas/metabolismo , Fosfatase Alcalina/metabolismo , Aminoácidos/metabolismo , Amilases/metabolismo , Ração Animal/análise , Aspartato Aminotransferases/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Celulose/metabolismo , Colesterol/metabolismo , Dieta , Peixes/metabolismo , Galactose/metabolismo , Glucose/metabolismo , Lipase/metabolismo , Metaboloma , Nucleotídeos/metabolismo , Pepsina A/metabolismo , Perciformes/fisiologia , Purinas/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Fator Estimulador de Colônias/metabolismo , Triglicerídeos/metabolismo , Tripsina/metabolismo , Triptaminas , Triptofano/metabolismo
20.
Fish Shellfish Immunol ; 130: 261-272, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36122639

RESUMO

Microplastic particles (MPs) are environmental pollutants that can cause varying levels of aquatic toxicity. Probiotics have been shown to reduce the negative effects of toxic substances. However, the protective effect of probiotics against the adverse effects of MPs has yet to be reported. The current study sought to determine the effects of the commercial probiotic AquaStar® Growout on polystyrene (PS)-MPs-mediated hepatic oxidative stress in Nile tilapia (Oreochromis niloticus). Fishes were assigned into four groups: the first group was the control, the second group was exposed to 1 mg/L of 0.5 µm PS-MPs, and the third and fourth groups were exposed to 1 mg/L of 0.5 µm PS-MPs and pre-fed with probiotics at levels of 3 g/kg and 6 g/kg diet, respectively. At the end of the experiment, probiotics administration reversed liver damage caused by the PS-MPs, reducing serum levels of malondialdehyde, aspartate aminotransferase, and alanine aminotransferase, and increasing the total antioxidant capacity. Furthermore, probiotics alleviated PS-MPs-induced oxidative stress by restoring antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase) and reducing oxidized glutathione and enhancing the redox state. Besides, probiotics supplementation decreased the transcriptional level of C-reactive protein and tumor necrosis factor-α following PS-MPs exposure. Furthermore, probiotics counteracted PS-MPs-associated reactive oxygen species production and mitogen-activated protein kinases (MAPKs) phosphorylation status. These findings suggested that probiotics could decrease liver damage caused by PS-MPs through their antioxidant properties and modulation of MAPK signaling pathways.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Ciclídeos , Poluentes Ambientais , Probióticos , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Proteína C-Reativa/metabolismo , Catalase/metabolismo , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Malondialdeído/metabolismo , Microplásticos/toxicidade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo , Plásticos , Polietileno , Poliestirenos , Probióticos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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