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1.
Int J Mol Sci ; 25(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38891998

RESUMO

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.


Assuntos
Proteínas do Citoesqueleto , Doxorrubicina , Camundongos Knockout , Podócitos , Animais , Humanos , Masculino , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , Podócitos/metabolismo , Podócitos/patologia , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética
2.
Molecules ; 28(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38138517

RESUMO

Obesity is an emerging global health issue with an increasing risk of disease linked to lifestyle choices. Previously, we reported that the hexane extract of Citrus sphaerocarpa (CSHE) suppressed lipid accumulation in differentiated 3T3-L1 adipocytes. In this study, we conducted in vivo experiments to assess whether CSHE suppressed obesity in zebrafish and mouse models. We administered 10 and 20 µg/mL CSHE to obese zebrafish juveniles. CSHE significantly inhibited visceral fat accumulation compared to untreated obese fish. Moreover, the oral administration (100 µg/g body weight/day) of CSHE to high-fat-diet-induced obese mice significantly reduced their body weight, visceral fat volume, and hepatic lipid accumulation. The expression analyses of key regulatory genes involved in lipid metabolism revealed that CSHE upregulated the mRNA expression of lipolysis-related genes in the mouse liver (Pparα and Acox1) and downregulated lipogenesis-related gene (Fasn) expression in epididymal white adipose tissue (eWAT). Fluorescence immunostaining demonstrated the CSHE-mediated enhanced phosphorylation of AKT, AMPK, ACC, and FoxO1, which are crucial factors regulating adipogenesis. CSHE-treated differentiated 3T3L1 adipocytes also exhibited an increased phosphorylation of ACC. Therefore, we propose that CSHE suppresses adipogenesis and enhances lipolysis by regulating the PI3K/AKT/FoxO1 and AMPK/ACC signaling pathways. These findings suggested that CSHE is a promising novel preventive and therapeutic agent for managing obesity.


Assuntos
Fármacos Antiobesidade , Citrus , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos Obesos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Peixe-Zebra/metabolismo , Adiposidade , Citrus/metabolismo , Fármacos Antiobesidade/farmacologia , Hexanos/farmacologia , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Adipogenia , Peso Corporal , Transdução de Sinais , Lipídeos/farmacologia , Dieta , Dieta Hiperlipídica/efeitos adversos , Células 3T3-L1 , Camundongos Endogâmicos C57BL
3.
Ecotoxicol Environ Saf ; 231: 113211, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35051758

RESUMO

Ultraviolet (UV) rays can be both harmful and beneficial to humans. This study aimed to investigate the toxicity and safety of ultraviolet C (UVC) exposure in living organisms and the corresponding biodefense molecular mechanisms. Zebrafish embryos, at an early developmental stage (5-6 h post-fertilization), were irradiated with increasing UVC dosages using high-efficiency deep-ultraviolet light-emitting diodes (278 nm). Morphological phenotypes including survival rate, hatching rate, heart rate, and malformation rate were evaluated. Compared to un-irradiated controls, all zebrafish embryos exposed to 4.5 mJ/cm2 UVC survived and showed no significant difference in hatching and heart rate. However, 7.5 mJ/cm2 of UVC irradiation caused a significantly decreased survival rate (37.5%) and an increased malformation rate (81.8%). Therefore, 4.5 mJ/cm2 was chosen as the limit dosage that the internal biodefense system of zebrafish embryos can protect against UVC radiation. Transcriptome analysis (RNA sequencing) performed on 3 min and 3 days post-irradiation embryos (4.5 mJ/cm2) revealed the molecular mechanisms underlying the response of zebrafish embryos to irradiation. The embryos quickly responded to UVC-induced stress by activating the p53 signaling pathway. In addition, after 3 days of recuperation, the embryos showed activation of signal transducer and activator of transcription (STAT) signaling pathway. To our knowledge, this is the first study to evaluate the toxicological effects and the molecular mechanism of biodefense in zebrafish embryos upon 278 nm UVC irradiation.


Assuntos
Embrião não Mamífero/efeitos da radiação , Transcriptoma , Raios Ultravioleta , Peixe-Zebra , Animais , Perfilação da Expressão Gênica , Peixe-Zebra/genética
4.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946279

RESUMO

Various natural products (NPs) have been used to treat obesity and related diseases. However, the best way to fight obesity is preventive, with accurate body weight management through exercise, diet, or bioactive NPs to avoid obesity development. We demonstrated that green tea extract (GTE) is an anti-obesity NP using a zebrafish obesity model. Based on a hypothesis that GTE can prevent obesity, the objective of this study was to assess GTE's ability to attenuate obesity development. Juvenile zebrafish were pretreated with GTE for seven days before obesity induction via a high-fat diet; adult zebrafish were pretreated with GTE for two weeks before obesity induction by overfeeding. As a preventive intervention, GTE significantly decreased visceral adipose tissue accumulation in juveniles and ameliorated visceral adiposity and plasma triglyceride levels in adult zebrafish obesity models. RNA sequencing analysis was performed using liver tissues from adult obese zebrafish, with or without GTE administration, to investigate the underlying molecular mechanism. Transcriptome analysis revealed that preventive GTE treatment affects several pathways associated with anti-obesity regulation, including activation of STAT and downregulation of CEBP signaling pathways. In conclusion, GTE could be used as a preventive agent against obesity.


Assuntos
Extratos Vegetais/farmacologia , Chá/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Biomarcadores , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
5.
Molecules ; 25(17)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878194

RESUMO

In recent decades, zebrafish (Danio rerio) has become a widely used vertebrate animal model for studying development and human diseases. However, studies on skin medication using zebrafish are rare. Here, we developed a novel protocol for percutaneous absorption of molecules via the zebrafish tail skin, by applying a liquid solution directly, or using a filter paper imbibed with a chemical solution (coating). Human skin is capable of absorbing felbinac and loxoprofen sodium hydrate (LSH), but not glycyrrhetinic acid (GA) and terbinafine hydrochloride (TH). To evaluate the possibility and the quality of transdermal absorption in zebrafish, we transdermally administered these four drugs to zebrafish. Pharmacokinetics showed that felbinac was present in the blood of zebrafish subjected to all administration methods. Felbinac blood concentrations peaked at 2 h and disappeared 7 h after administration. GA was not detected following transdermal administrations, but was following exposure. LSH was not found in the circulatory system after transdermal administration, but TH was. A dose-response correlation was observed for felbinac blood concentration. These findings suggest that zebrafish are capable of absorbing drug molecules through their skin. However, the present data cannot demonstrate that zebrafish is a practical model to predict human skin absorption. Further systemic studies are needed to observe the correlations in percutaneous absorption between humans and zebrafish.


Assuntos
Preparações Farmacêuticas/metabolismo , Absorção Cutânea , Administração Cutânea , Animais , Ácido Glicirretínico/administração & dosagem , Ácido Glicirretínico/farmacocinética , Peixe-Zebra
6.
Molecules ; 25(7)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244349

RESUMO

Ceramides have several well-known biological properties, including anti-pigmentation and anti-melanogenesis, which make them applicable for use in skincare products in cosmetics. However, the efficacy of ceramides is still limited. Dermal or transdermal drug delivery systems can enhance the anti-pigmentation properties of ceramides, although there is currently no systemic evaluation method for the efficacy of these systems. Here we prepared several types of lecithin-based emulsion of maize-derived glucosylceramide, determining PC70-ceramide (phosphatidylcholine-base) to be the safest and most effective anti-pigmentation agent using zebrafish larvae. We also demonstrated the efficacy of PC70 as a drug delivery system by showing that PC70-Nile Red (red fluorescence) promoted Nile Red accumulation in the larval bodies. In addition, PC70-ceramide suppressed melanin in mouse B16 melanoma cells compared to ceramide alone. In conclusion, we developed a lecithin-based dermal delivery method for ceramide using zebrafish larvae with implications for human clinical use.


Assuntos
Ceramidas/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lecitinas/química , Pigmentação/efeitos dos fármacos , Zea mays/química , Animais , Ceramidas/química , Melanoma Experimental , Camundongos , Pigmentação da Pele/efeitos dos fármacos , Peixe-Zebra
7.
Molecules ; 25(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33322023

RESUMO

(1) Background: The obesity epidemic has been drastically progressing in both children and adults worldwide. Pharmacotherapy is considered necessary for its treatment. However, many anti-obesity drugs have been withdrawn from the market due to their adverse effects. Instead, natural products (NPs) have been studied as a source for drug discovery for obesity, with the goal of limiting the adverse effects. Zebrafish are ideal model animals for in vivo testing of anti-obesity NPs, and disease models of several types of obesity have been developed. However, the evidence for zebrafish as an anti-obesity drug screening model are still limited. (2) Methods: We performed anti-adipogenic testing using the juvenile zebrafish obesogenic test (ZOT) and mouse 3T3-L1 preadipocytes using the focused NP library containing 38 NPs and compared their results. (3) Results: Seven and eleven NPs reduced lipid accumulation in zebrafish visceral fat tissues and mouse adipocytes, respectively. Of these, five NPs suppressed lipid accumulation in both zebrafish and 3T3-L1 adipocytes. We confirmed that these five NPs (globin-digested peptides, green tea extract, red pepper extract, nobiletin, and Moringa leaf powder) exerted anti-obesity effects in diet-induced obese adult zebrafish. (4) Conclusions: ZOT using juvenile fish can be a high-throughput alternative to ZOT using adult zebrafish and can be applied for in vivo screening to discover novel therapeutics for visceral obesity and potentially also other disorders.


Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Camundongos , Peixe-Zebra
8.
Molecules ; 24(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500159

RESUMO

Green tea is a popular beverage that is rich in polyphenolic compounds such as catechins. Its major content, (-)-epigallocatechin-3-gallate, has been shown to have beneficial effects on several diseases including cancer, metabolic syndrome, cardiovascular diseases, and neurodegenerative diseases. The aim of this study was to assess the anti-obesity effects and the underlying molecular mechanisms of green tea extract (GTE) using zebrafish larva and adult obesity models. We administered 100 µg/mL GTE to zebrafish larvae and performed a short-term obesogenic test. GTE significantly decreased the visceral adipose tissue volume induced by a high-fat diet. Oral administration (250 µg/g body weight/day) of GTE to adult diet-induced obese zebrafish also significantly reduced their visceral adipose tissue volume, with a reduction of plasma triglyceride and total cholesterol levels. To investigate the molecular mechanism underlying the GTE effects, we conducted RNA sequencing using liver tissues of adult zebrafish and found that GTE may ameliorate the obese phenotypes via the activation of Wnt/ß-catenin and adenosine monophosphate-activated protein kinase (AMPK) pathway signaling. In addition, the comparative transcriptome analysis revealed that zebrafish and mammals may share a common molecular response to GTE. Our findings suggest that daily consumption of green tea may be beneficial for the prevention and treatment of obesity.


Assuntos
Antioxidantes/farmacologia , Obesidade/dietoterapia , Chá/química , Transcriptoma/efeitos dos fármacos , Quinases Proteína-Quinases Ativadas por AMP , Animais , Antioxidantes/química , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Obesidade/genética , Obesidade/patologia , Proteínas Quinases/genética , RNA-Seq , Transcriptoma/genética , Via de Sinalização Wnt/genética , Peixe-Zebra
9.
Dis Model Mech ; 17(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747698

RESUMO

Diabetic nephropathy (DN), as a complication of diabetes, is a substantial healthcare challenge owing to the high risk of morbidity and mortality involved. Although significant progress has been made in understanding the pathogenesis of DN, more efficient models are required to develop new therapeutics. Here, we created a DN model in zebrafish by crossing diabetic Tg(acta1:dnIGF1R-EGFP) and proteinuria-tracing Tg(l-fabp::VDBP-GFP) lines, named zMIR/VDBP. Overfed adult zMIR/VDBP fish developed severe hyperglycemia and proteinuria, which were not observed in wild-type zebrafish. Renal histopathology revealed human DN-like characteristics, such as glomerular basement membrane thickening, foot process effacement and glomerular sclerosis. Glomerular dysfunction was restored upon calorie restriction. RNA sequencing analysis demonstrated that DN zebrafish kidneys exhibited transcriptional patterns similar to those seen in human DN pathogenesis. Notably, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated, a phenomenon observed in the early phase of human DN. In addition, metformin improved hyperglycemia and proteinuria in DN zebrafish by modulating Akt phosphorylation. Our results indicate that zMIR/VDBP fish are suitable for elucidating the mechanisms underlying human DN and could be a powerful tool for therapeutic discovery.


Assuntos
Nefropatias Diabéticas , Modelos Animais de Doenças , Hiperglicemia , Proteinúria , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Peixe-Zebra , Animais , Hiperglicemia/complicações , Hiperglicemia/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Animais Geneticamente Modificados , Metformina/farmacologia , Metformina/uso terapêutico , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Ativação Enzimática/efeitos dos fármacos
10.
Food Sci Nutr ; 12(6): 4342-4352, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873438

RESUMO

Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as Monostroma nitidum that exhibits various biological functions, including anticoagulant, antitumour, antiviral, and anti-obesity properties. In our previous clinical trial, we demonstrated that RS intake improves constipation. However, no specific bacteria showed a significant (p < .05) change. Notably, these results were obtained after a short RS inoculation period of only 2 weeks. In the present study, to evaluate the long-term effects of RS on the gut microbiota, we orally administered RS to BALB/c mice for 11 weeks, analyzed their blood biochemical data, and performed 16s rRNA-sequencing. Oral administration of RS increased body weight with increased food intake, whereas plasma total cholesterol and fasting plasma glucose levels decreased. RS-fed mice showed lower fasting insulin levels (p < .1) and decreased homeostatic model assessment for insulin resistance (HOMA-IR, p < .0001), suggesting that RS improved insulin resistance. In the feces of mice, the amounts of acetic and propionic acids increased. In the gut microbiota, predictive metagenomic profiling using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) revealed functional alterations in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways in RS-fed mice. Corresponding to the blood glucose-lowering effect, the glycolysis and tricarboxylic acid (TCA) cycle pathways were activated. In addition, the Firmicutes/Bacteroides (F/B) ratio, which may be associated with various health outcomes, was also reduced. These results suggest that the blood glucose-lowering effect, improvement in insulin resistance, and lipid-lowering effect of RS may be due to changes in the intestinal microbiota.

11.
Front Nutr ; 10: 1173225, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396125

RESUMO

Metabolic syndrome comprises a group of conditions that collectively increase the risk of abdominal obesity, diabetes, atherosclerosis, cardiovascular diseases, and cancer. Gut microbiota is involved in the pathogenesis of metabolic syndrome, and microbial diversity and function are strongly affected by diet. In recent years, epidemiological evidence has shown that the dietary intake of seaweed can prevent metabolic syndrome via gut microbiota modulation. In this review, we summarize the current in vivo studies that have reported the prevention and treatment of metabolic syndrome via seaweed-derived components by regulating the gut microbiota and the production of short-chain fatty acids. Among the surveyed related articles, animal studies revealed that these bioactive components mainly modulate the gut microbiota by reversing the Firmicutes/Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria, such as Bacteroides, Akkermansia, Lactobacillus, or decreasing the abundance of harmful bacteria, such as Lachnospiraceae, Desulfovibrio, Lachnoclostridium. The regulated microbiota is thought to affect host health by improving gut barrier functions, reducing LPS-induced inflammation or oxidative stress, and increasing bile acid production. Furthermore, these compounds increase the production of short-chain fatty acids and influence glucose and lipid metabolism. Thus, the interaction between the gut microbiota and seaweed-derived bioactive components plays a critical regulatory role in human health, and these compounds have the potential to be used for drug development. However, further animal studies and human clinical trials are required to confirm the functional roles and mechanisms of these components in balancing the gut microbiota and managing host health.

12.
Front Microbiol ; 14: 1079187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36876090

RESUMO

Interventions to the gut microbiome manipulate the gut-brain axis and could be useful in the treatment of anxiety and depression. In this study, we demonstrated that administration of the bacterium Paraburkholderia sabiae reduces anxiety-like behavior in adult zebrafish. P. sabiae administration increased the diversity of the zebrafish gut microbiome. Linear discriminant analysis Effect Size (LEfSe) analysis revealed that the populations of Actinomycetales including Nocardiaceae, Nocardia, Gordoniaceae, Gordonia, Nakamurellaceae, and Aeromonadaceae were reduced, whereas those of Rhizobiales including Xanthobacteraceae, Bradyrhizobiaceae, Rhodospirillaceae, and Pirellulaceae were increased in the gut microbiome. Functional analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) predicted that P. sabiae administration altered taurine metabolism in the zebrafish gut, and we demonstrated that P. sabiae administration increased the taurine concentration in the brain. Since taurine functions as an antidepressant neurotransmitter in vertebrates, our results suggest that P. sabiae could improve anxiety-like behavior in zebrafish via the gut-brain axis.

13.
Cells ; 12(22)2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37998401

RESUMO

Oral administration of rhamnan sulfate (RS), derived from the seaweed Monostroma nitidum, markedly suppresses inflammatory damage in the vascular endothelium and organs of lipopolysaccharide-treated mice. This study aimed to analyze whether orally administered RS inhibits the development of atherosclerosis, a chronic inflammation of the arteries. ApoE-deficient female mice were fed a normal or high-fat diet (HFD) with or without RS for 12 weeks. Immunohistochemical and mRNA analyses of atherosclerosis-related genes were performed. The effect of RS on the migration of RAW264.7 cells was also examined in vitro. RS administration suppressed the increase in blood total cholesterol and triglyceride levels. In the aorta of HFD-fed mice, RS reduced vascular smooth muscle cell proliferation, macrophage accumulation, and elevation of VCAM-1 and inhibited the reduction of Robo4. Increased mRNA levels of Vcam1, Mmp9, and Srebp1 in atherosclerotic areas of HFD-fed mice were also suppressed with RS. Moreover, RS directly inhibited the migration of RAW264.7 cells in vitro. Thus, in HFD-fed ApoE-deficient mice, oral administration of RS ameliorated abnormal lipid metabolism and reduced vascular endothelial inflammation and hyperpermeability, macrophage infiltration and accumulation, and smooth muscle cell proliferation in the arteries leading to atherosclerosis. These results suggest that RS is an effective functional food for the prevention of atherosclerosis.


Assuntos
Aterosclerose , Clorófitas , Animais , Feminino , Camundongos , Dieta Hiperlipídica , Sulfatos , Aterosclerose/metabolismo , Inflamação/metabolismo , Clorófitas/genética , Administração Oral , Apolipoproteínas E , RNA Mensageiro/uso terapêutico , Receptores de Superfície Celular
14.
Sci Total Environ ; 835: 155436, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35461948

RESUMO

The ubiquity of microplastic/nanoplastics (MP/NPs) provides an opportunity for their interaction with other widely spread environmental contaminants. MP/NP and nanoparticles share a similar transport route from sources, production, and disposal. Metal oxide nanoparticles (nMOx) have varied industrial applications, and limited knowledge is available on their interaction with MP/NPs. The present study investigated the effect of NPs (1 mg/L) on the efflux of two nMOx, aluminium oxide nanoparticles (nAl2O3, 1 mg/L) and cerium oxide nanoparticles (nCeO2, 1 mg/L), and their combined toxicity to zebrafish embryos. The results illustrated increased accumulation of aluminium and cerium in the combined exposure group compared to the nMOx alone treatment. The presence of NPs exacerbated the oxidative stress caused by nAl2O3 and nCeO2, as evidenced by an increase in the concentration of reactive oxygen species (ROS), alteration of antioxidants, and lipid peroxidation. The integrated biomarker response (IBRv2) values showed the induction of an antioxidative response in NP + nAl2O3, whereas a decline in IBRv2 values was observed in NP + nCeO2. Our results indicate that NPs aggravated the accumulation of nMOx and their toxicity. The present work highlights that more attention should be paid to the discharge of these contaminants into the natural environment.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Animais , Antioxidantes/metabolismo , Nanopartículas Metálicas/toxicidade , Microplásticos , Nanopartículas/toxicidade , Estresse Oxidativo , Óxidos/toxicidade , Plásticos , Peixe-Zebra/metabolismo
15.
Food Sci Nutr ; 10(4): 1248-1256, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35432980

RESUMO

The zebrafish obesogenic test (ZOT) is a powerful tool for identifying anti-adipogenic compounds for in vivo screening. In our previous study, we found that Moringa oleifera (MO) leaf powder suppressed the accumulation of visceral adipose tissue (VAT) in ZOT. MO demonstrates a wide range of pharmacological effects; however, little is known about its functional constituents. To identify the anti-adipogenic components of MO leaves, we prepared extracts using different extraction methods and tested the obtained extracts and fractions using ZOT. We found that the dichloromethane extract and its hexane:EtOAc = 8:2 fraction reduced VAT accumulation in young zebrafish fed a high-fat diet. We also performed gene expression analysis in the zebrafish VAT and found that CCAAT/enhancer-binding protein beta and CCAAT/enhancer-binding protein delta (associated with early stages of adipogenesis) gene expression was downregulated after fraction 2 administration. We identified a new MO fraction that suppressed VAT accumulation by inhibiting early adipogenesis using the ZOT. Phenotype-driven zebrafish screening is a reasonable strategy for identifying bioactive components in natural products.

16.
Sci Total Environ ; 800: 149463, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399343

RESUMO

The ubiquity of nanoplastics (NPs) raises concerns about their interactions and combined toxicity with other common contaminants. Although azoles are present throughout the natural environment, their interactions with NP are not well known. We investigated the effects of polystyrene (PS) NP on the toxicity of ketoconazole (KCZ) and fluconazole (FCZ) in zebrafish embryos using the developmental toxicity, oxidative-stress-related biochemical parameters, and expression of genes related to neurotoxicity (ache), cardiotoxicity (gata4, bmp4), inflammation (il1b), oxidative stress (sod1, sod2, cyp1a), and apoptosis (bax, bcl2). Co-exposure to NP (1 mg/L) and KCZ/FCZ (1 mg/L) for 96 h reduced the hatching rate, survival rate, and heart rate and increased the malformation rate and catalase activity. The bax/bcl2 ratio, an apoptosis indicator, was higher after NP, KCZ, or FCZ treatment. However, the bax/bcl2 ratio after exposure to NP + KCZ or NP + FCZ was much higher than that after single exposure. Overall, the results indicated that NP aggravated the toxicity of azole by significantly increasing the reactive oxygen species, lipid peroxidation and altering the expression of oxidative-stress- and apoptosis-related genes. The interactive toxicity of PS NP with KCZ/FCZ reported in this study emphasises the need for caution in the release of azole fungicides in the environment.


Assuntos
Azóis , Fungicidas Industriais , Microplásticos , Poluentes Químicos da Água , Animais , Azóis/metabolismo , Azóis/toxicidade , Embrião não Mamífero/metabolismo , Fluconazol/metabolismo , Fluconazol/toxicidade , Fungicidas Industriais/metabolismo , Fungicidas Industriais/toxicidade , Cetoconazol/metabolismo , Cetoconazol/toxicidade , Estresse Oxidativo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
17.
Sci Rep ; 11(1): 13384, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226572

RESUMO

Rhamnan sulphate (RS), a sulphated polysaccharide from Monostroma nitidum, possesses several biological properties that help in treating diseases such as viral infection, thrombosis, and obesity. In the present study, we first administered RS (0.25 mg/g food volume) orally to high-fat diet-treated mice for 4 weeks. RS increased the faecal volume and calorie excretion with decreased plasma lipids, which was in accordance with the results of our previous zebrafish study. Notably, as the excretion amount by RS increased in the mice, we hypothesised that RS could decrease the chance of constipation in mice and also in human subjects because RS is considered as a dietary fibre. We administrated RS (100 mg/day) to subjects with low defaecation frequencies (3-5 times/week) for 2 weeks in double-blind placebo-controlled manner. As a result, RS administration significantly increased the frequency of dejection without any side effects, although no effect was observed on the body weight and blood lipids. Moreover, we performed 16s rRNA-seq analysis of the gut microbiota in these subjects. Metagenomics profiling using PICRUSt revealed functional alternation of the KEGG pathways, which could be involved in the therapeutic effect of RS for constipation.


Assuntos
Bactérias/isolamento & purificação , Clorófitas/química , Constipação Intestinal/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Adulto , Idoso , Animais , Constipação Intestinal/microbiologia , Código de Barras de DNA Taxonômico , Método Duplo-Cego , Feminino , Humanos , Masculino , Metagenômica , Camundongos , Pessoa de Meia-Idade , Adulto Jovem
18.
Front Cell Dev Biol ; 9: 588093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748100

RESUMO

Osteoporosis is the most common aging-associated bone disease and is caused by hyperactivation of osteoclastic activity. We previously reported that the hexane extract of ginger rhizome [ginger hexane extract (GHE)] could suppress receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. However, the anti-osteoclastic components in GHE have not yet been identified. In this study, we separated GHE into several fractions using silica gel column chromatography and evaluated their effects on osteoclastogenesis using a RAW264.7 cell osteoclast differentiation assay (in vitro) and the zebrafish scale model of osteoporosis (in vivo). We identified that the fractions containing 10-gingerol suppressed osteoclastogenesis in RAW264.7 cells detected by tartrate-resistant acid phosphatase (TRAP) staining. In zebrafish, GHE and 10-gingerol suppressed osteoclastogenesis in prednisolone-induced osteoporosis regenerated scales to promote normal regeneration. Gene expression analysis revealed that 10-gingerol suppressed osteoclast markers in RAW264.7 cells [osteoclast-associated immunoglobulin-like receptor, dendrocyte-expressed seven transmembrane protein, and matrix metallopeptidase-9 (Mmp9)] and zebrafish scales [osteoclast-specific cathepsin K (CTSK), mmp2, and mmp9]. Interestingly, nuclear factor of activated T-cells cytoplasmic 1, a master transcription regulator of osteoclast differentiation upstream of the osteoclastic activators, was downregulated in zebrafish scales but showed no alteration in RAW264.7 cells. In addition, 10-gingerol inhibited CTSK activity under cell-free conditions. This is the first study, to our knowledge, that has found that 10-gingerol in GHE could suppress osteoclastic activity in both in vitro and in vivo conditions.

19.
Front Nutr ; 8: 650975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646848

RESUMO

Globin digest (GD), a bioactive oligopeptide derived from porcine hemoglobin proteins, has been demonstrated to have beneficial effects on improving postprandial hyperlipidemia, hyperglycemia, and liver injury. We previously reported the lipid-lowering effects of GD using a zebrafish obesogenic test. Here, we sought to evaluate the effect of GD on visceral adiposity and the underlying molecular mechanisms using zebrafish and mouse obesity models. GD ameliorated dyslipidemia and suppressed the accumulation of visceral adipose tissue (VAT) in adult obese zebrafish. Transcriptomic analysis by RNA sequencing of GD-treated adult zebrafish revealed that GD upregulated UCP1-related pathways. Further, we performed mouse experiments and found that GD intake (2 mg/g body weight/day) was associated with lowered plasma triglyceride and total cholesterol levels, decreased VAT accumulation, and improved adipocyte hypertrophy with the upregulation of Ucp1 expression in white adipose tissue at both the mRNA and protein levels. Taken together, these results indicate that GD improves visceral adiposity by upregulating UCP1 expression, providing a novel perspective on combating obesity.

20.
BMC Physiol ; 10: 21, 2010 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-20961460

RESUMO

BACKGROUND: Obesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO). RESULTS: Zebrafish were assigned into two dietary groups. One group of zebrafish was overfed with Artemia (60 mg dry weight/day/fish), a living prey consisting of a relatively high amount of fat. The other group of zebrafish was fed with Artemia sufficient to meet their energy requirements (5 mg dry weight/day/fish). Zebrafish were fed under these dietary protocols for 8 weeks. The zebrafish overfed with Artemia exhibited increased body mass index, which was calculated by dividing the body weight by the square of the body length, hypertriglyceridemia and hepatosteatosis, unlike the control zebrafish. Calorie restriction for 2 weeks was applied to zebrafish after the 8-week overfeeding period. The increased body weight and plasma triglyceride level were improved by calorie restriction. We also performed comparative transcriptome analysis of visceral adipose tissue from DIO zebrafish, DIO rats, DIO mice and obese humans. This analysis revealed that obese zebrafish and mammals share common pathophysiological pathways related to the coagulation cascade and lipid metabolism. Furthermore, several regulators were identified in zebrafish and mammals, including APOH, IL-6 and IL-1ß in the coagulation cascade, and SREBF1, PPARα/γ, NR1H3 and LEP in lipid metabolism. CONCLUSION: We established a zebrafish model of DIO that shared common pathophysiological pathways with mammalian obesity. The DIO zebrafish can be used to identify putative pharmacological targets and to test novel drugs for the treatment of human obesity.


Assuntos
Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Obesidade/etiologia , Obesidade/fisiopatologia , Animais , Modelos Animais de Doenças , Humanos , Mamíferos , Transdução de Sinais , Peixe-Zebra
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