RESUMO
Environmental pollutants, including polychlorinated biphenyls (PCBs), act as endocrine disruptors and impair various physiological processes. PCB 126 is associated with steatohepatitis, fibrosis, cirrhosis, and other hepatic injuries. These disorders can be regulated by microRNAs (miRNAs). Therefore, this study aimed to investigate the role of miRNAs in non-alcoholic fatty liver disease associated with exposure to PCB 126. Adult male C57BL/6 mice were exposed to PCB 126 (5 µmol/kg of body weight) for 10 weeks. The PCB group showed lipid accumulation in the liver in the presence of macro- and microvesicular steatosis and fibrosis with increased inflammatory and profibrotic gene expression, consistent with non-alcoholic steatohepatitis (NASH). PCB exposure also upregulated miR-155 and miR-34a, which induce the expression of proinflammatory cytokines and inflammation in the liver and reduce the expression of peroxisome proliferator-activated receptor α, which, in turn, impairs lipid oxidation and hepatic steatosis. Therefore, the present study showed that PCB 126 induced NASH via potential mechanisms involving miR-155 and miR-34a, which may contribute to the development of new diagnostic markers and therapeutic strategies.
Assuntos
Cirrose Hepática , Camundongos Endogâmicos C57BL , MicroRNAs , Bifenilos Policlorados , Regulação para Cima , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Bifenilos Policlorados/toxicidade , Masculino , Camundongos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Regulação para Cima/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Poluentes Ambientais/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genéticaRESUMO
BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.
Assuntos
Medula Óssea , Desferroxamina , Ferritinas , Sobrecarga de Ferro , Ferro , Fígado , Diálise Renal , Humanos , Masculino , Feminino , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/metabolismo , Medula Óssea/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Ferritinas/sangue , Ferritinas/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/diagnóstico por imagem , Pessoa de Meia-Idade , Desferroxamina/uso terapêutico , Desferroxamina/administração & dosagem , Ferro/metabolismo , Idoso , Imageamento por Ressonância Magnética , Estudos Prospectivos , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/sangue , Fator de Crescimento de Fibroblastos 23 , Hepcidinas/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera (Moringaceae family), commonly known as horseradish or tree of life, is traditionally used for various diseases, such as diabetes, hypercholesterolemia, neurological disorders, among others. AIM OF THE STUDY: To evaluate the toxicological profile of the oral use of an aqueous extract of Moringa oleifera leaves for 13 weeks in mice. MATERIALS AND METHODS: Initially, a factorial design (23) was carried out to optimize aqueous extraction using as variables; the extraction method and proportion of drug. The 13-week repeated-dose toxicity trial used female and male mice, with oral administration of aqueous extract of Moringa oleifera leaves at doses of 250, 500, and 1000 mg/kg. The animals were evaluated for body weight, water and feed intake, biochemical and hematological parameters, urinalysis, ophthalmology and histopathology of the liver, spleen and kidneys. RESULTS: The extraction efficiency was evidenced by the extraction by maceration at 5%, obtaining the optimized extract of Moringa oleifera (OEMo). The oral administration of OEMo did not promote significant difference (p > 0.05) in the weight gain, food and water consumption of the control animals and those treated with 250 and 500 mg/kg. However, treatment with 1000 mg/kg promoted a reduction (p < 0.05) in food intake and body weight from the 7th week onwards in male and female mice. No alterations were detected in the hematological and histological parameters in the concentrations tested for both sexes. The highest concentration treatment (1000 mg/kg) promoted an increase in transaminases in males and females. All concentrations promoted a significant decrease (p < 0.05) in the serum lipid profile of mice. CONCLUSION: This study developed an optimized extract of Moringa oleifera leaves, which should be used with caution in preparations above 500 mg/kg for the long term because it leads to significant changes in liver enzymes. On the other hand, the extract proved to be a promising plant preparation for hyperlipidemia in mice.
Assuntos
Moringa oleifera , Extratos Vegetais , Folhas de Planta , Animais , Moringa oleifera/química , Extratos Vegetais/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Masculino , Feminino , Camundongos , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/patologia , Administração Oral , Rim/efeitos dos fármacos , Rim/patologiaRESUMO
This study investigated the antitumoral, anti-inflammatory and oxidative effects of polysaccharides from tucum (Bactris setosa, TUC) using the Ehrlich carcinoma as a tumor model. Additionally, the glycogen content, cytochrome P levels, and gluconeogenesis from lactate were assessed in the liver of healthy animals. Tumor-bearing female mice were orally treated with 50 and 100 mg.kg-1 of TUC or vehicle, once a day, or with 1.5 mg.kg-1 methotrexate via i.p., every 3 days, along 21 days. Both doses of TUC reduced the tumor weight and volume. In the tumor tissue, it decreased GSH and IL-1ß levels, and increased LPO, NAG, NO and TNF-α levels. The tumor histology showed necrosis and leukocytes infiltration. The metabolic effects of TUC were investigated by measurement of total cytochrome P (CYP) and glycogen in tumor-bearing mice, and by ex vivo liver perfusion on non-bearing tumor male mice, using lactate as gluconeogenic precursor. Metabolically, the hepatic glucose and pyruvate productions, oxygen uptake, and the total CYP concentration were not modified by TUC. Thus, tucum-do-cerrado polysaccharides have antitumor effects through the modulation of oxidative stress and inflammation, without impairing glucose production from lactate in the liver, the main organ responsible for the metabolism of organic and xenobiotic compounds.
Assuntos
Gluconeogênese , Fígado , Polissacarídeos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Gluconeogênese/efeitos dos fármacos , Feminino , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/química , Estresse Oxidativo/efeitos dos fármacos , Frutas/química , Glicogênio/metabolismo , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
Senescent cells have been linked to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effectiveness of senolytic drugs in reducing liver damage in mice with MASLD is not clear. Additionally, MASLD has been reported to adversely affect male reproductive function. Therefore, this study aimed to evaluate the protective effect of senolytic drugs on liver damage and fertility in male mice with MASLD. Three-month-old male mice were fed a standard diet (SD) or a choline-deficient western diet (WD) until 9 months of age. At 6 months of age mice were randomized within dietary treatment groups into senolytic (dasatinib + quercetin [D + Q]; fisetin [FIS]) or vehicle control treatment groups. We found that mice fed choline-deficient WD had liver damage characteristic of MASLD, with increased liver size, triglycerides accumulation, fibrosis, along increased liver cellular senescence and liver and systemic inflammation. Senolytics were not able to reduce liver damage, senescence and systemic inflammation, suggesting limited efficacy in controlling WD-induced liver damage. Sperm quality and fertility remained unchanged in mice developing MASLD or receiving senolytics. Our data suggest that liver damage and senescence in mice developing MASLD is not reversible by the use of senolytics. Additionally, neither MASLD nor senolytics affected fertility in male mice.
Assuntos
Fertilidade , Flavonóis , Quercetina , Senoterapia , Animais , Masculino , Camundongos , Fertilidade/efeitos dos fármacos , Quercetina/farmacologia , Senoterapia/farmacologia , Flavonóis/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Senescência Celular/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Dieta Ocidental/efeitos adversos , Progressão da Doença , Deficiência de Colina/complicações , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Roundup Transorb® (RDT) is the most popular glyphosate-based herbicide (GHB) used in agriculture, and its impact extends to non-target organisms. The annual killifish Austrolebias charrua is an endangered species endemic to southern South America and inhabits temporary ponds. This study evaluates the effects of RDT concentrations (0.065 and 5 mg/L GAE) on A. charrua exposed for 96 h. Gene expression of cat, sod2, gstα, gclc, and ucp1 was evaluated on the liver and gills. Highlighting that even at low concentrations permitted by Brazilian legislation, the RDT can have adverse effects on A. charrua.
Assuntos
Antioxidantes , Glicina , Glifosato , Herbicidas , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Herbicidas/toxicidade , Glicina/análogos & derivados , Glicina/toxicidade , Projetos Piloto , Fundulidae/genética , Expressão Gênica/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Brasil , Brânquias/metabolismo , Peixes ListradosRESUMO
OBJECTIVE: Cisplatin, a widely used anticancer agent, induces hepatotoxicity alongside organ damage. Understanding Cisplatin's toxicity mechanism and developing preventive measures are crucial. Our study explores Myricetin, a flavonoid, for its protective effects against Cisplatin-induced hepatotoxicity. METHODS: In our study, a total of 32 Wistar albino male rats were utilized, which were categorized into four distinct groups: Control, Myricetin, Cisplatin, and Myricetin+Cisplatin. For the histological assessment of hepatic tissues, hematoxylin-eosin and periodic acid Schiff staining were employed, alongside immunohistochemical measurements of TNF-α, interleukin-17, and interleukin-6 immunoreactivity. Additionally, aspartate transaminase and alanine transaminase values were examined by biochemical analysis. RESULTS: In the histological evaluation of the tissues, a normal healthy cell structure and a strong periodic acid Schiff (+) reaction were observed in the hepatocyte cells in the tissues of the Control and Myricetin groups, while intense eosinophilia, minimal vacuolization, congestion, and sinusoidal expansions were observed in the hematoxylin-eosin stainings, and a decrease in the positive reaction in the periodic acid Schiff staining was observed in the Cisplatin group. Consistent with these histological findings, an increase in TNF-α, interleukin-17, and interleukin-6 expressions (p<0.0001) and a concomitant increase in aspartate transaminase and alanine transaminase values were observed in the Cisplatin group. In the group protected by Myricetin, a significant improvement was observed in all these histological and biochemical values. CONCLUSION: Cisplatin induces notable histopathological alterations in the liver. In this context, Myricetin exhibits the potential to alleviate Cisplatin-induced damage by modulating histological parameters and biochemical processes.
Assuntos
Alanina Transaminase , Antineoplásicos , Aspartato Aminotransferases , Doença Hepática Induzida por Substâncias e Drogas , Cisplatino , Flavonoides , Interleucina-6 , Ratos Wistar , Fator de Necrose Tumoral alfa , Animais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Cisplatino/toxicidade , Masculino , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/patologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/toxicidade , Interleucina-6/análise , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos , Interleucina-17/metabolismo , Imuno-HistoquímicaRESUMO
Producers of fish have been looking for viable alternatives for the management of Colossoma macropomum (tambaqui) in confinement systems in order to avoid the harm and subsequent losses caused by parasitic diseases. One alternative used by farmers is pesticides, such as trichlorfon, which has a genotoxic effect. Thus, this study aimed to evaluate the changes in gene expression due to the side effects of trichlorfon in tambaqui. Two treatments were used based on LC50-96h of 0.870 mg/L using 30% and 50% trichlorfon with exposure periods of 48, 72 and 96 h. For differential expression of the genes in the liver, real-time PCR was performed for the AChE, GST, CYP2J6, CYP2C8, 18S and GAPDH genes. After 96 h of exposure to trichlorfon, an alteration in the gene expression profile of the antioxidant defense system (GST) of the tambaqui was observed. It was also observed that this organophosphate did not affect the expression of genes related to the isoenzymes that are responsible for the biotransformation of xenobiotics in phase I (2J6 and 2C8) and cholinesterase AChE. It was concluded that the reduction in gene expression of GST suggests a decrease in metabolization capacity in phase II.
Assuntos
Caraciformes , Triclorfon , Animais , Triclorfon/toxicidade , Biomarcadores , Reação em Cadeia da Polimerase em Tempo Real , Poluentes Químicos da Água/toxicidade , Fígado/efeitos dos fármacos , Fatores de Tempo , Inseticidas/toxicidadeRESUMO
The objective of the present study was to explore the influence of dietary supplementation with a mixed additive (MA) containing a probiotic and anti-mycotoxin (Saccharomyces cerevisiae RC016 and Lactobacillus rhamnosus RC007) and its interaction on the performance and health (biochemistry and liver/intestine histopathology) of broilers fed diets contaminated with aflatoxin B1 (AFB1) at 506000±22.1ng/kg. The MA contained S. cerevisiae RC016 (1×107cells/g) and L. rhamnosus RC007 (1×108cells/g) in relation 1:1. A total of sixty-one-day-old Cobb broilers were randomly allocated into four treatment groups with three replicates of 5 birds each for a five-week-old feeding experiment. The experimental diet for each treatment (T) was formulated as follows: T1, a commercial diet (CD); T2, CD+AFB1; T3, CD+0.1% MA; T4, CD+AFB1+0.1% MA. The MA improved (p<0.01) production parameters (weight gain, conversion rate, and carcass yield) and reduced (p<0.01) the toxic effect of AFB1 on the relative weight of the livers. In addition, the macro and microscopic alterations of livers and the possible intestinal injury related to histological damage in the presence of mycotoxin were reduced. The use of probiotic MA based on S. cerevisiae RC016 and L. rhamnosus RC007 in animal feed provides greater protection against mycotoxin contamination and is safe for use as a supplement in animal feed, providing beneficial effects that improve animal health and productivity. This is of great importance at the economic level for the avian production system.
Assuntos
Aflatoxina B1 , Ração Animal , Galinhas , Contaminação de Alimentos , Lacticaseibacillus rhamnosus , Probióticos , Saccharomyces cerevisiae , Animais , Aflatoxina B1/toxicidade , Galinhas/microbiologia , Suplementos Nutricionais , Fígado/efeitos dos fármacos , Fígado/patologiaRESUMO
INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.