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1.
Braz. j. biol ; 84: e253731, 2024. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1355871

RESUMO

Abstract Petroleum water soluble fraction (WSF) impairs organisms, but damages may vary among cell and tissue levels. The aim of the present study was to evaluate the acute (24 h, 48 h, 72 h) and subchronic effects (36 days) of WSF (0%, 25% and 100%) in juveniles of the Neotropical top predator fish Hoplias aff. malabaricus. The effects of WSF were evaluated at a molecular level using the comet assay and micronucleus test for genome damage; and at a morphological level through histological identification of liver pathologic lesions. In both acute and subchronic exposure we found low levels of DNA damage (< 10% of comet tail) and non-significant frequency of micronucleus in WSF exposed fish. The most significant liver lesions in WSF exposed fish were fatty vacuolization, hypertrophy and focal necrosis. Since these tissue injuries were progressive and persistent, their irreversibility may negatively affect fish recruitment, even in a such resistant top predator.


Resumo A fração solúvel de petróleo (WSF) prejudica os organismos, porém os danos podem variar entre os níveis celular e tecidual. O objetivo do presente estudo foi avaliar o efeito agudo (24 h, 48 h e 72 h) e subcrônico (36 dias) da WSF (0%, 25% e 100%) em juvenis do peixe neotropical predador topo Hoplias aff. malabaricus. Os efeitos da WSF foram avaliados no nível molecular utilizando o ensaio do cometa e o teste do micronúcleo para o dano genômico e no nível morfológico através da identificação histológica de lesões patológicas no fígado. Em ambas exposições (aguda e subcrônica) encontramos baixos níveis de dano no DNA (< 10% de DNA na cauda do cometa) e frequência de micronúcleos não significativa em peixes expostos a WSF. As lesões mais significativas no fígado dos peixes expostos a WSF foram a vacuolização lipídica, hipertrofia e focos de necroses. Como estas lesões foram progressivas e persistentes, sua irreversibilidade pode afetar negativamente o recrutamento dos peixes, mesmo sendo um predador topo resistente.


Assuntos
Animais , Poluentes Químicos da Água/toxicidade , Petróleo/toxicidade , Caraciformes , Água Doce , Fígado
2.
Braz. j. biol ; 83: e248755, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1350303

RESUMO

Abstract Consuming a high-fat diet causes a harmful accumulation of fat in the liver, which may not reverse even after switching to a healthier diet. Different reports dealt with the role of purslane as an extract against high-fat diet; meanwhile, it was necessary to study the potential role of fresh purslane as a hypolipidemic agent. This study is supposed to investigate further the potential mechanism in the hypolipidemic effect of fresh purslane, by measuring cholesterol 7a-hydroxylase (CYP7A1) and low-density lipoprotein receptor (Ldlr). Rats were divided into two main groups: the first one is the normal control group (n=7 rats) and the second group (n=28 rats) received a high fat diet for 28 weeks to induce obesity. Then the high fat diet group was divided into equal four subgroups. As, the positive control group still fed on a high fat diet only. Meanwhile, the other three groups were received high-fat diet supplemented with a different percent of fresh purslane (25, 50 and 75%) respectively. At the end of the experiment, rats were sacrificed and samples were collected for molecular, biochemical, and histological studies. Current study reported that, supplementation of fresh purslane especially at a concentration of 75% play an important role against harmful effects of high-fat diet at both cellular and organ level, by increasing CYP7A1 as well as Ldlr mRNA expression. Also, there were an improvement on the tested liver functions, thyroid hormones, and lipid profile. Fresh purslane plays the potential role as a hypolipidemic agent via modulation of both Ldlr and Cyp7A, which will point to use fresh purslane against harmful effects of obesity.


Resumo O consumo de uma dieta rica em gordura causa um acúmulo prejudicial de gordura no fígado, que pode não reverter mesmo após a mudança para uma dieta mais saudável. Diferentes relatórios trataram do papel da beldroega como um extrato contra uma dieta rica em gordura; entretanto, foi necessário estudar o papel potencial da beldroega fresca como agente hipolipemiante. Este estudo pretende investigar mais profundamente o mecanismo potencial no efeito hipolipidêmico da beldroega fresca, medindo o colesterol 7a-hidroxilase (CYP7A1) e o receptor de lipoproteína de baixa densidade (Ldlr). Os ratos foram divididos em dois grupos principais: o primeiro é o grupo controle normal (n = 7 ratos) e o segundo grupo (n = 28 ratos) recebeu dieta rica em gorduras por 28 semanas para induzir a obesidade. Em seguida, o grupo de dieta rica em gordura foi dividido em quatro subgrupos iguais. Como, o grupo de controle positivo ainda se alimentava apenas com dieta rica em gordura. Enquanto isso, os outros três grupos receberam dieta rica em gordura suplementada com diferentes porcentagens de beldroegas frescas (25%, 50% e 75%), respectivamente. Ao final do experimento, os ratos foram sacrificados e amostras coletadas para estudos moleculares, bioquímica e histológicos. O estudo atual relatou que a suplementação de beldroegas frescas, especialmente a uma concentração de 75%, desempenha papel importante contra os efeitos prejudiciais da dieta rica em gordura em nível celular e orgânico, aumentando a expressão de CYP7A1 e Ldlr mRNA. Além disso, houve melhora nas funções hepáticas testadas, nos hormônios tireoidianos e no perfil lipídico. Beldroegas frescas desempenham papel potencial como agente hipolipemiante por meio da modulação de Ldlr e Cyp7A, o que apontará para o uso de beldroegas frescas contra os efeitos nocivos da obesidade.


Assuntos
Animais , Ratos , Portulaca , Dieta Hiperlipídica/efeitos adversos , Hipolipemiantes , Colesterol 7-alfa-Hidroxilase , Ratos Sprague-Dawley , Fígado
3.
Braz. j. biol ; 83: e247190, 2023. graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1345532

RESUMO

Abstract The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.


Resumo O presente estudo teve como objetivo avaliar o potencial antioxidante e o efeito inibitório de Cannabis sativa e Morus nigra contra a peroxidação lipídica em homogenatos de cérebro e fígado de cabras. A formação de radicais livres, espécies altamente reativas de oxigênio (ROS) e espécies reativas de nitrogênio (RNS), é um processo metabólico normal para sinalização celular e combate aos antígenos. No entanto, eles podem causar sérios danos se forem produzidos em portagens ampliadas. Além disso, distúrbios metabólicos também servem como fontes dessas espécies reativas, embora o problema possa ser resolvido por meio de suplementos e outros fitoquímicos. Neste estudo, duas espécies de plantas foram avaliadas quanto ao seu potencial biológico, empregando um espectro de ensaios antioxidantes. A atividade antioxidante foi realizada por ensaio de peroxidação lipídica. O extrato de água preparado a partir de folhas de Cannabis sativa e Morus nigra mostrou inibição significativa (P < 0,05) em comparação com o controle, ou seja, 522,6 ± 0,06 e 659,97 ± 0,03 µg / mL contra peroxidação lipídica induzida por ferro em homogenato de cérebro de cabra, enquanto as inibições foram 273,54 ± 0,04 e 309,18 ± 0,05 µg / mL contra a peroxidação lipídica do cérebro induzida por nitroprussiato. A peroxidação lipídica induzida por ferro e nitroprussiato também foi significativamente inibida por extratos de folhas de Cannabis sativa e Morus nigra em homogenatos de fígado, como 230,63 ± 0,52 e 326,91 ± 0,01 µg / mL (induzida por ferro), enquanto 300,47 ± 0,07 e 300,47 ± 0,07 µg / mL (induzida por nitroprussiato), respectivamente. Os extratos do extrato de Cannabis sativa apresentaram atividade promissora (96,04 ± 0,060%) contra os radicais DPPH enquanto Morus nigra apresentou atividade moderada (34,11 ± 0,120%). Os resultados sugerem que diferentes acessos de Cannabis sativa e Morus nigra são uma fonte potencial de antioxidantes e têm efeito terapêutico contra doenças induzidas por estresse oxidativo e, portanto, podem ser usados ​​para a descoberta e desenvolvimento de novos medicamentos.


Assuntos
Animais , Cannabis , Morus , Encéfalo , Cabras , Extratos Vegetais/farmacologia , Peroxidação de Lipídeos , Fígado , Antioxidantes/metabolismo , Antioxidantes/farmacologia
4.
Braz. j. biol ; 83: e244551, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1285626

RESUMO

Abstract Origanum vulgare has been of great interest in academia and pharma industry due to its antioxidant, antifungal and antitumor properties. The present study aimed to find the anti-MRSA potential and in vivo toxicity assessments of O. vulgare. O. vulgare extract was used to monitor anti-MRSA activity in mice. Following MRSA established infection in mice (Mus musculus), treatment with O. vulgare was continued for 7 days. Autopsies were performed and re-isolation, gross lesion scoring and bacterial load in various organs were measured. Additionally, blood sample was analysed for hematological assays. Toxicity assessment of O. vulgare potential as medicine was done at 200 mg/kg and 400 mg/kg by evaluating liver and kidney functions. Bacterial load and gross lesion in lungs and heart were significantly low compared to positive control following O. vulgare treatment. Likewise, O. vulgare treated groups had hematological, neutrophil and TLC values similar to control groups. Increased AST, ALP and total bilirubin alongwith marked hepatocellular degeneration and distortion around the central vein, inflammatory cell infiltration, and cytoplasmic vacuolization of hepatic cells was observed at higher dose. It is concluded that crude extract of O. vulgare may contain beneficial secondary metabolites and in future may be explored for curing infectious diseases.


Resumo Origanum vulgare tem despertado grande interesse na academia e na indústria farmacêutica devido às suas propriedades antioxidantes, antifúngicas e antitumorais. O presente estudo teve como objetivo encontrar o potencial anti-MRSA e avaliações de toxicidade in vivo de O. vulgare. O extrato de O. vulgare foi usado para monitorar a atividade anti-MRSA em camundongos. Após infecção estabelecida por MRSA em camundongos (Mus musculus), o tratamento com O. vulgare foi continuado por 7 dias. As autópsias foram realizadas e o reisolamento, pontuação das lesões grosseiras e carga bacteriana em vários órgãos foram medidos. Além disso, a amostra de sangue foi analisada para ensaios hematológicos. A avaliação da toxicidade do potencial de O. vulgare como medicamento foi feita com 200 mg / kg e 400 mg / kg, avaliando as funções hepática e renal. A carga bacteriana e as lesões graves nos pulmões e no coração foram significativamente baixas em comparação com o controle positivo após o tratamento com O. vulgare. Da mesma forma, os grupos tratados com O. vulgare apresentaram valores hematológicos, de neutrófilos e de TLC semelhantes aos grupos de controle. Aumento de AST, ALP e bilirrubina total juntamente com degeneração hepatocelular marcada e distorção ao redor da veia central, infiltração de células inflamatórias e vacuolização citoplasmática de células hepáticas foram observados em doses mais altas. Conclui-se que o extrato bruto de O. vulgare pode conter metabólitos secundários benéficos e, no futuro, pode ser explorado para a cura de doenças infecciosas.


Assuntos
Animais , Coelhos , Óleos Voláteis , Origanum , Anti-Infecciosos/toxicidade , Extratos Vegetais/toxicidade , Fígado , Antioxidantes
5.
Braz. j. biol ; 83: e244784, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1278541

RESUMO

Abstract The work aimed to evaluate the weight-length relationship and the condition factor, characterizing the biometry, anatomy, histology and volumetric density of the liver of Brycon amazonicus, in different stages of body growth. The experiment used twenty specimens in four stages of body growth (PI, PII, PIII and PIV) harvested every 90 days, containing five specimens, each group. The livers were dissected, weighed (g) and processed routinely using the hematoxylin and eosin technique. The data were submitted to analysis of variance, Pearson's correlation test and linear regression. The equation that represented the weight-length relation was W = 0.05902 x L2.63, with negative allometric growth, but with a relative condition factor equal to 1.0. The liver was divided into three lobes with the gallbladder close to the right lobe and its color varied from light red to dark red, not varying in relation to other fish species. The hepatosomatic relationship followed body growth until the PII group stage and then declined, demonstrating the behavior of its development in Brycon amazonicus. The organ consists predominantly of hepatocytes, followed by sinusoidal vessels and capillaries, with histological morphology similar to that of many species of fish. Melanomacrophage centers were found only in the most developed animals, but in small quantities, prompting the development of new research on this cell, in this species. In this way, research of this nature allows the characterization of fish species, helping to improve breeding methods, understanding pathological processes caused by diseases, and obtaining better productive capacity, serving an increasingly demanding and prosperous market.


Resumo O trabalho objetivou avaliar a relação peso-comprimento e o fator de condição, caracterizando a biometria, anatomia, histologia e densidade volumétrica do fígado de Brycon amazonicus, em diferentes estágios de crescimento corporal. O experimento utilizou vinte espécimes em quatro fases de crescimento corporal (PI, PII, PIII e PIV) colhidos a cada 90 dias, contendo cinco espécimes, cada grupo. Os fígados foram dissecados, pesados (g) e processados rotineiramente pela técnica da hematoxilina e eosina. Os dados foram submetidos à análise de variância, teste de correlação de Pearson e regressão linear. A equação que representou a relação peso-comprimento foi W = 0,05902 x L2,63, com crescimento alométrico negativo, mas com fator de condição relativo igual a 1,0. O fígado apresentou-se dividido em três lobos com a vesícula biliar próxima ao lobo direito e sua cor variou de vermelho claro a vermelho escuro, não variando em relação a outras espécies de peixes. A relação hepatossomática acompanhou o crescimento corporal até a fase do grupo PII e então declinou, demonstrando o comportamento de seu desenvolvimento em Brycon amazonicus. O órgão constitui-se predominantemente por hepatócitos, seguido de vasos e capilares sinusoidais, com a morfologia histológica semelhante ao de muitas espécies de peixes. Centros melanomacrófagos foram encontrados apenas nos animais mais desenvolvidos, mas em pequena quantidade, instigando o desenvolvimento de novas pesquisas sobre esta célula, nesta espécie. Desta forma, pesquisas desta natureza permitem a caracterização de espécies de peixes, auxiliando no aperfeiçoamento de métodos de criação, compreensão de processos patológicos provocados por enfermidades, e obtenção de melhor capacidade produtiva, atendendo um mercado cada vez mais exigente e próspero.


Assuntos
Animais , Caraciformes , Fígado
6.
Int J Mol Med ; 49(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35137921

RESUMO

The aim of the present study was to elucidate the effect of resveratrol on non­alcoholic steatohepatitis (NASH), and the molecular basis in mice and Hepa1­6 cells, in order to verify its therapeutic effect. C57BL/6J mice were fed a methionine­choline­deficient (MCD) diet to induce steatohepatitis and were treated with resveratrol. Mouse sera were collected for biochemical analysis and enzyme­linked immunosorbent assay, and livers were obtained for histological observation, and mmu­microRNA (miR)­599 and inflammation­related gene expression analysis. Hepa1­6 cells were treated with palmitic acid to establish a NASH cell model, and were then treated with resveratrol, or transfected with mmu­miR­599 mimic, mmu­miR­599 inhibitor or recombinant pregnane X receptor (PXR) plasmid. Subsequently, the cells were collected for mmu­miR­599 and inflammation­related gene expression analysis. Reverse transcription­quantitative polymerase chain reaction and western blotting were used to assess mmu­miR­599 expression levels, and the mRNA and protein expression levels of PXR and inflammation­related genes. The binding site of mmu­miR­599 in the PXR mRNA was verified by the luciferase activity assay. Mice fed an MCD diet for 4 weeks exhibited steatosis, focal necrosis and inflammatory infiltration in the liver. Resveratrol significantly reduced serum aminotransferase and malondialdehyde levels, and ameliorated hepatic injury. These effects were associated with reduced mmu­miR­599 expression, enhanced PXR expression, and downregulated levels of nuclear factor­κB, tumour necrosis factor­α, interleukin (IL)­1ß, IL­6, NOD­like receptor family pyrin domain­containing protein 3 and signal transducer and activator of transcription 3. Administration of the mmu­miR­599 mimic inhibited PXR expression in Hepa1­6 cells, whereas the mmu­miR­599 inhibitor exerted the opposite effect. A binding site for mmu­miR­599 was identified in the PXR mRNA sequence. Furthermore, overexpression of PXR inhibited the expression of inflammatory factors in Hepa1­6 cells. The present study provided evidence for the protective role of resveratrol in ameliorating steatohepatitis through regulating the mmu­miR­599/PXR pathway and the consequent suppression of related inflammatory factors. Resveratrol may serve as a potential candidate for steatohepatitis management.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor de Pregnano X/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico
7.
Bioanalysis ; 14(5): 267-278, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35195037

RESUMO

Background: The degree of human hepatocyte replacement in chimeric mice with humanized liver has previously been shown to correlate with human plasma albumin measurements. However, there are no reports that directly compare the remaining endogenous mouse albumin with the newly expressed human albumin following engraftment. To better understand the disposition of serum albumin in PXB-mice, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to simultaneously quantitate both human and mouse albumin from plasma. Results: A robust correlation was observed between the serum human albumin levels measured by LC-MS/MS and the estimated replacement index of PXB-mice. Conclusion: All data were shown to be specific and suitable to accurately quantify both human and mouse albumin from plasma of chimeric mice with humanized livers.


Assuntos
Albumina Sérica Humana , Espectrometria de Massas em Tandem , Quimera , Cromatografia Líquida , Hepatócitos , Humanos , Fígado , Espectrometria de Massas em Tandem/métodos
8.
Environ Pollut ; 302: 119062, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35231537

RESUMO

Lead is a metal that exists naturally in the Earth's crust and is a ubiquitous environmental contaminant. The alleviation of lead toxicity is important to keep human health under lead exposure. Biosynthesized selenium nanoparticle (SeNPs) and selenium-enriched Lactobacillus rhamnosus SHA113 (Se-LRS) were developed in this study, and their potentials in alleviating lead-induced injury to the liver and intestinal tract were evaluated in mice by oral administration for 4 weeks. As results, oral intake of lead acetate (150 mg/kg body weight per day) caused more than 50 times and 100 times lead accumulation in blood and the liver, respectively. Liver function was seriously damaged by the lead exposure, which is indicated as the significantly increased lipid accumulation in the liver, enhanced markers of liver function injury in serum, and occurrence of oxidative stress in liver tissues. Serious injury in intestinal tract was also found under lead exposure, as shown by the decrease of intestinal microbiota diversity and occurrence of oxidative stress. Except the lead content in blood and the liver were lowered by 52% and 58%, respectively, oral administration of Se-LRS protected all the other lead-induced injury markers to the normal level. By the comparison with the effects of normal L. rhamnosus SHA113 and the SeNPs isolated from Se-LRS, high protective effects of Se-LRS can be explained as the extremely high efficiency to promote lead excretion via feces by forming insoluble mixture. These findings illustrate the developed selenium-enriched L. rhamnosus can efficiently protect the liver and intestinal tract from injury by lead.


Assuntos
Enteropatias , Lactobacillus rhamnosus , Selênio , Animais , Chumbo/toxicidade , Fígado , Camundongos , Selênio/farmacologia
9.
Aliment Pharmacol Ther ; 56(2): 209-223, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35661191

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors known to regulate glucose and fatty acid metabolism, inflammation, endothelial function and fibrosis. PPAR isoforms have been extensively studied in metabolic diseases, including type 2 diabetes and cardiovascular diseases. Recent data extend the key role of PPARs to liver diseases coursing with vascular dysfunction, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). AIM: This review summarises and discusses the pathobiological role of PPARs in cardiovascular diseases with a special focus on their impact and therapeutic potential in NAFLD and NASH. RESULTS AND CONCLUSIONS: PPARs may be attractive for the treatment of NASH due to their liver-specific effects but also because of their efficacy in improving cardiovascular outcomes, which may later impact liver disease. Assessment of cardiovascular disease in the context of NASH trials is, therefore, of the utmost importance, both from a safety and efficacy perspective.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Receptores Ativados por Proliferador de Peroxissomo/uso terapêutico
11.
Sci Total Environ ; 840: 156668, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35710014

RESUMO

Microplastics (MPs) have infiltrated human food system globally, and the latent health risks have been well-described. However, the impact of pre-consumed MPs on liver resistance to foreign robust stimuli remains unclear. In this study, we developed a mouse model drinking roughly 18 and 180 µg/kg/day polystyrene MPs for 90 days, then intraperitoneally injected mice with 80 mg/kg cyclophosphamide (CTX) to investigate whether chronic pre-exposure to MPs aggravates hepatoxicity induced by CTX. Slight liver injury was found in single CTX-treated mice, while more significant liver histopathological damage, inflammation and oxidative stress elicited by CTX were observed in pre-drinking MPs mice. Moreover, chronic exposure of MPs induced remarkable colonic impairments (e.g., leaky gut, mild inflammation and repressed antioxidant activity) as well as gut microbiota perturbation, which manifested positive association with aggravated hepatotoxicity via spearman correlation analysis. Fecal microbiota transplantation (FMT) trail was conducted to ulteriorly demonstrate the critical role of MPs-altered gut bacteria in exaggerated liver susceptibility to CTX stimulation. In conclusion, our study provided an insight that the adverse impact of MPs could be best revealed when animals suffering attack from hazardous substance. It also contributes to comprehensive assessment of health risk from environmentally pervasive MPs.


Assuntos
Microbioma Gastrointestinal , Microplásticos , Animais , Ciclofosfamida/toxicidade , Inflamação , Fígado , Camundongos , Plásticos/toxicidade , Poliestirenos/toxicidade
12.
Transpl Int ; 35: 10460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711320

RESUMO

The effectiveness of liver transplantation to cure numerous diseases, alleviate suffering, and improve patient survival has led to an ever increasing demand. Improvements in preoperative management, surgical technique, and postoperative care have allowed increasingly complicated and high-risk patients to be safely transplanted. As a result, many patients are safely transplanted in the modern era that would have been considered untransplantable in times gone by. Despite this, more gains are possible as the science behind transplantation is increasingly understood. Normothermic machine perfusion of liver grafts builds on these gains further by increasing the safe use of grafts with suboptimal features, through objective assessment of both hepatocyte and cholangiocyte function. This technology can minimize cold ischemia, but prolong total preservation time, with particular benefits for suboptimal grafts and surgically challenging recipients. In addition to more physiological and favorable preservation conditions for grafts with risk factors for poor outcome, the extended preservation time benefits operative logistics by allowing a careful explant and complicated vascular reconstruction when presented with challenging surgical scenarios. This technology represents a significant advancement in graft preservation techniques and the transplant community must continue to incorporate this technology to ensure the benefits of liver transplant are maximized.


Assuntos
Transplante de Fígado , Preservação de Órgãos , Isquemia Fria/efeitos adversos , Humanos , Fígado/cirurgia , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos
13.
Oxid Med Cell Longev ; 2022: 6520789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720183

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is an inevitable result of liver surgery. Steatotic livers are extremely sensitive to IRI and have worse tolerance. Ferroptosis is considered to be one of the main factors of organ IRI. This study is aimed at exploring the role of ferroptosis in the effect of heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) on steatotic liver IRI and its mechanism. An IRI model of a steatotic liver and a hypoxia reoxygenation (HR) model of steatotic hepatocytes (SHPs) were established. Rat BMMSCs were extracted and transfected with the Ho1 gene to establish HO-1/BMMSCs, and their exosomes were extracted by ultracentrifugation. Ireb2 was knocked down to verify its role in ferroptosis and cell injury in SHP-HR. Public database screening combined with quantitative real-time reverse transcription PCR identified microRNAs (miRNAs) targeting Ireb2 in HO-1/BMMSCs exosomes. miR-29a-3p mimic and inhibitor were used for functional verification experiments. Liver function, histopathology, terminal deoxynulceotidyl transferase nick-end-labeling staining, cell viability, mitochondrial membrane potential, and cell death were measured to evaluate liver tissue and hepatocyte injury. Ferroptosis was assessed by detecting the levels of IREB2, Fe2+, malondialdehyde, glutathione, lipid reactive oxygen species, glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2 mRNA, and mitochondrial morphology. The results revealed that HO-1/BMMSCs improved liver tissue and hepatocyte injury and suppressed ferroptosis in vivo and in vitro. The expression of IREB2 was increased in steatotic liver IRI and SHP-HR. Knocking down Ireb2 reduced the level of Fe2+ and inhibited ferroptosis. HO-1/BMMSC exosomes reduced the expression of IREB2 and inhibited ferroptosis and cell damage. Furthermore, we confirmed high levels of miR-29a-3p in HO-1/BMMSCs exosomes. Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis. Downregulation of miR-29a-3p blocked the protective effect of HO-1/BMMSC exosomes on SHP-HR cell injury. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic liver IRI. HO-1/BMMSCs could suppress ferroptosis by targeting Ireb2 via the exosomal transfer of miR-29a-3p.


Assuntos
Exossomos , Fígado Gorduroso , Ferroptose , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Animais , Apoptose , Exossomos/metabolismo , Fígado Gorduroso/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Proteína 2 Reguladora do Ferro/metabolismo , Fígado/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Traumatismo por Reperfusão/patologia
14.
Front Immunol ; 13: 788935, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720395

RESUMO

Background: Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP. Methods: Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student's t-test. Results: Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion. Conclusions: Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.


Assuntos
Transplante de Fígado , Citocinas , Humanos , Fígado , Doadores Vivos , Preservação de Órgãos , Perfusão
15.
Adipocyte ; 11(1): 366-378, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35734881

RESUMO

High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance.


Assuntos
Resistência à Insulina , Receptor IGF Tipo 1 , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Anticorpos Monoclonais Humanizados , Dieta Hiperlipídica/efeitos adversos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores
16.
Food Chem ; 393: 133443, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751216

RESUMO

Polyphenols in vinegar are benefit to human health. The purpose of this research was to identify the polyphenols-rich vinegar extract (VE) and evaluate the anti-diabetic mechanisms in vivo. The results showed that 29 polyphenols were identified by UPLC-Q/Trap-MS/MS analysis. 4-Hydroxybenzoic acid, ferulic acid, and ethyl ferulate were the main polyphenols. In addition, VE relieved the symptoms of type 2 diabetes mellitus (T2DM) by down-regulating blood glucose and lipemia. VE reduced inflammation by inhibiting TLR4/NF-κB signaling pathway. Furthermore, VE treatment restored gut microbiota dysbiosis (upregulating Bacteroidetes, Lactobacillus, Bifidobacterium, and Bacteroides and downregulating Firmicutes, Proteobacteria, and Enterorhabdus abundances), and increased short chain fatty acids contents in diabetic mice, which participated in anti-diabetic effect of VE by correlation analysis. These findings suggest that VE may be a candidate for T2DM intervention by regulating gut microbiota and inflammation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Ácido Acético/farmacologia , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/tratamento farmacológico , Fígado/metabolismo , Camundongos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Espectrometria de Massas em Tandem
17.
J Pak Med Assoc ; 72(6): 1080-1085, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35751313

RESUMO

OBJECTIVE: To evaluate the pattern of equiliberative nucleoside transporters in viral hepatitis responding and non-responding patients, to correlate the liver fibrosis stage with the pattern among the non-responders, and to correlate the equiliberative nucleoside transporter status with housekeeping hypoxanthine-guanine phosphoribosyltransferase gene. Method: The comparative cross-sectional study was conducted at the Molecular Biology and Genetics Department, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, from March to August 2018, and comprised adult hepatitis C virus patients of either gender who completed six months of treatment. They were assessed for response to therapy in terms of the presence of the viral load in their serum by using real time polymerase chain reaction, and divided into responder group A and non-responder group B. The groups were compared and correlation between equiliberative nucleoside transporter expressions and liver fibrosis was evaluated. Data was analysed using SPSS 23. RESULTS: Of the 80 patients, 33(41.3%) were males and 47(58.8%) were females. The overall mean age was 37.46±10.61 years. In terms of response to treatment, there were 40(50%) in each of the two groups. Mean post-treatment duration was 15.38±30.09 weeks. Age was not significantly different with respect to gender (p>0.05), but the age pattern was significantly different between the two groups (p<0.001). Also, non-responders had significant post-treatment duration compared to the responders (p<0.001). Hypoxanthine-guanine phosphoribosyltransferase gene showed no significant difference between the groups (p=0.144). Equiliberative nucleoside transporter was significantly down-regulated in the non-responders (p<0.001) and showed correlation with the degree of liver fibrosis (p<0.034) compared to the responders. CONCLUSIONS: There was a significant association between equiliberative nucleoside transporters and liver fibrosis stage in hepatitis C virus non-responding patients.


Assuntos
Hepatite C Crônica , Hepatite C , Adulto , Antivirais/uso terapêutico , Estudos Transversais , Feminino , Hepacivirus/genética , Hepatite C/complicações , Hepatite C Crônica/complicações , Humanos , Hipoxantina Fosforribosiltransferase , Fígado/patologia , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte de Nucleosídeos/genética , Nucleosídeos/uso terapêutico
18.
Comput Intell Neurosci ; 2022: 7954333, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755754

RESUMO

Liver segmentation and recognition from computed tomography (CT) images is a warm topic in image processing which is helpful for doctors and practitioners. Currently, many deep learning methods are used for liver segmentation that takes a long time to train the model which makes this task challenging and limited to larger hardware resources. In this research, we proposed a very lightweight convolutional neural network (CNN) to extract the liver region from CT scan images. The suggested CNN algorithm consists of 3 convolutional and 2 fully connected layers, where softmax is used to discriminate the liver from background. Random Gaussian distribution is used for weight initialization which achieved a distance-preserving-embedding of the information. The proposed network is known as Ga-CNN (Gaussian-weight initialization of CNN). General experiments are performed on three benchmark datasets including MICCAI SLiver'07, 3Dircadb01, and LiTS17. Experimental results show that the proposed method performed well on each benchmark dataset.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
19.
J Environ Public Health ; 2022: 7826396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755887

RESUMO

Background: Intentional ingestion of organophosphate (OP) and carbamate is a significant health issue worldwide. It causes adverse health effects on the liver. This study aimed to determine liver transaminases (AST and ALT) and bilirubin levels to assess the severity of poisoning in patients with acute OP and carbamate poisoning. Methods: A descriptive cross-sectional study was conducted on patients admitted to a selected hospital in Sri Lanka with acute OP and carbamate poisoning. The severity of poisoning was measured by RBC cholinesterase and Peradeniya Organophosphorus Poisoning scale (POP), where six clinical features were assessed based on a 3-point scale. A score of 0-3 was considered mild, 4-7 to be moderate, and 8-11 to be severe poisoning. Liver parameters such as AST, ALT, and total and direct bilirubin were measured. Results: Among the 188 screened patients, 166 were recruited. Majority were males (112, 67.5%). Kruskal-Wallis test showed significant differences in AST and ALT on admission and AST on discharge, across POP groups ((χ 2 (2, n = 166) = 26.48, p ≤ 0.001), (χ 2 (2, n = 166) = 14.31, p=0.001), and (χ 2 (2, n = 157) = 11.34, p=0.003), respectively)). Mann-Whitney U test showed significantly higher AST and ALT in the moderate POP group compared to the mild POP group (AST: U = 1709, z = -4.50, p ≤ 0.001, r = 0.36; ALT: U = 2114, z = -3.04, p=0.002, r = 0.26) on admission. In addition, the treatment outcomes (duration of hospital stay and duration of ventilator assistance) were significantly correlated (p ≤ 0.001) with the severity of poisoning and serum AST and ALT at the time of admission. Conclusion: AST and ALT levels on admission and AST level at discharge showed significant correlations with the severity of poisoning. Treatment outcomes significantly correlated with the severity of poisoning and serum AST and ALT levels.


Assuntos
Carbamatos , Organofosfatos , Bilirrubina , Estudos Transversais , Feminino , Humanos , Fígado , Masculino , Estudos Prospectivos
20.
Front Endocrinol (Lausanne) ; 13: 868572, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757434

RESUMO

Obesity, altered glucose homeostasis, hyperinsulinism, and reproductive dysfunction develops in female humans and mammals with hyperandrogenism. We previously reported that low dose dihydrotestosterone (DHT) administration results in metabolic and reproductive dysfunction in the absence of obesity in female mice, and conditional knock-out of the androgen receptor (Ar) in the liver (LivARKO) protects female mice from DHT-induced glucose intolerance and hyperinsulinemia. Since altered metabolic function will regulate reproduction, and liver plays a pivotal role in the reversible regulation of reproductive function, we sought to determine the reproductive phenotype of LivARKO mice under normal and hyperandrogenemic conditions. Using Cre/Lox technology, we deleted the Ar in the liver, and we observed LivARKO female mice have normal puberty timing, cyclicity and reproductive function. After DHT treatment, like control mice, LivARKO experience altered estrous cycling, reduced numbers of corpus lutea, and infertility. Liver Ar is not involved in hyperandrogenemia-induced reproductive dysfunction. The reproductive dysfunction in the DHT-treated LivARKO lean females with normal glucose homeostasis indicates that androgen-induced reproductive dysfunction is independent from metabolic dysfunction.


Assuntos
Hiperandrogenismo , Síndrome do Ovário Policístico , Animais , Di-Hidrotestosterona , Feminino , Glucose , Humanos , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/genética , Hiperandrogenismo/metabolismo , Fígado/metabolismo , Mamíferos/metabolismo , Camundongos , Obesidade , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Receptores Androgênicos/metabolismo
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