• CYP2E1
• Molecular simulation
• Organophosphorus flame retardant
• Species-specific metabolism

• Animals
• Carps/metabolism
• Humans
• Rats
• Flame Retardants/toxicity
• Flame Retardants/metabolism
• Molecular Docking Simulation
• Cytochrome P-450 CYP2E1/metabolism
• Hydroxylation
• Organophosphates/metabolism
• Organophosphates/toxicity
• Species Specificity
• Microsomes, Liver/metabolism
• Water Pollutants, Chemical/metabolism
• Water Pollutants, Chemical/toxicity

• P20 GM121310 NIGMS NIH HHS
• R03 NS136719 NINDS NIH HHS

• Alcoholic fatty liver disease
• Gut microbiotas
• Jiuzao polysaccharides
• Zebrafish larvae

• Alcoholic liver disease
• Endoplasmic reticulum stress
• Hepatocyte apoptosis
• Unfolded protein response

• Humans
• Endoplasmic Reticulum Stress
• Liver Diseases, Alcoholic/etiology
• Fatty Liver/complications
• Ethanol/adverse effects
• Inflammation/complications

• alcoholic liver disease
• gut-liver
• metabolism
• nanoparticle mediated treatment
• stress mechanism

• Humans
• Carcinoma, Hepatocellular/etiology
• Liver Neoplasms/etiology
• Liver Diseases, Alcoholic/etiology
• Liver Diseases, Alcoholic/therapy
• Ethanol

• Animals
• Child
• Humans
• Liver Cirrhosis/genetics
• Mannose-6-Phosphate Isomerase
• Phenotype
• Transcriptome/genetics
• Zebrafish/genetics

• R01 DK121154 NIDDK NIH HHS
• R01 DK123758 NIDDK NIH HHS
• National Institute of Diabetes and Digestive and Kidney Diseases

• alcoholic liver disease
• endotoxin
• hepatoprotective
• inflammation
• lipid metabolism
• the extract from Rumex hanus by.

• Animals
• Chemical and Drug Induced Liver Injury, Chronic
• Endotoxins
• Ethanol/adverse effects
• Ethanol/metabolism
• Humans
• Liver/metabolism
• Liver Diseases, Alcoholic/drug therapy
• Liver Diseases, Alcoholic/prevention & control
• Mice
• Plant Extracts/metabolism
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Rumex

Alcoholism is a well-known risk factor for liver injury and is one of the major causes of hepatic steatosis worldwide. Although many drugs have been reported to have protective effects against acute alcohol-induced hepatotoxicity, there is limited available treatment for alcoholic liver disease (ALD), indicating an urgent need for effective therapeutic options. Herein, we first reported the protective effects of magnesium isoglycyrrhizinate (MgIG) on acute alcohol-induced hepatic steatosis and its related mechanisms in a zebrafish model.

Alcohol was administered directly to embryo medium at 5 days post-fertilization (dpf) for up to 32 h. MgIG was given to the larvae 2 h before the administration of alcohol and then cotreated with alcohol starting at 5 dpf. Oil red O staining was used to determine the incidence of steatosis, and pathological features of the liver were assessed by hematoxylin–eosin staining. Biological indexes, total cholesterol (TC) and triacylglycerol (TG) were detected in the livers of zebrafish larvae. Morphological changes in the livers of zebrafish larvae were observed using liver-specific EGFP transgenic zebrafish (Tg(lfabp10a:eGFP)). The expression levels of critical molecules related to endoplasmic reticulum (ER) stress and lipid metabolism were detected by qRT–PCR, whole-mount in situ hybridization and western blotting.

Alcohol-treated larvae developed hepatomegaly and steatosis after 32 h of exposure. We found that MgIG improved hepatomegaly and reduced the incidence of steatosis in a dose-dependent manner by oil red O staining and diminished deposits of alcohol-induced fat droplets by histologic analysis. Moreover, MgIG significantly decreased the levels of TC and TG in the livers of zebrafish larvae. Furthermore, the expression levels of critical genes involved in ER stress (atf6, irela, bip, chop) and the key enzymes regulating lipid metabolism (acc1, fasn, hmgcs1 and hmgcra) were significantly higher in the alcohol-treated group than in the control group. However, in the MgIG plus alcohol-treated group, the expression of these genes was markedly decreased compared with that in the alcohol-treated group. Whole-mount in situ hybridization and western blotting also showed that MgIG had an effect on the expression levels of critical genes and proteins involved in lipid metabolism and ER stress. Our results revealed that MgIG could markedly regulate these genes and protect the liver from ER stress and lipid metabolism disorders.

Our study is the first to demonstrate that MgIG could protect the liver from acute alcohol stimulation by ameliorating the disorder of lipid metabolism and regulating ER stress in zebrafish larvae.

The online version contains supplementary material available at 10.1186/s12986-022-00655-7.

• Alcoholic liver disease
• Hepatic steatosis
• Magnesium isoglycyrrhizinate
• Zebrafish

• ER associated degradation
• ER-lysosomal degradation
• ER-phagy
• alcoholic liver disease
• alpha-1 antitrypsin disease
• fibrosis
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis

• K01 DK112915 NIDDK NIH HHS
• American Association for the Study of Liver Diseases
• National Institutes of Health

• 3R
• alternative methods
• danio rerio
• organ toxicity
• transgenic animals

• Animal Testing Alternatives/methods
• Animals
• Embryo, Nonmammalian/metabolism
• Humans
• Larva/metabolism
• Models, Animal
• Toxicity Tests/methods
• Zebrafish/metabolism

• P-066 Stiftung zur Förderung der Erforschung von Ersatz- und Ergänzungsmethoden zur Einschränkung von Tierversuchen

Since its debut in the biomedical research fields in 1981, zebrafish have been used as a vertebrate model organism in more than 40,000 biomedical research studies. Especially useful are zebrafish lines expressing fluorescent proteins in a molecule, intracellular organelle, cell or tissue specific manner because they allow the visualization and tracking of molecules, intracellular organelles, cells or tissues of interest in real time and in vivo. In this review, we summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, the nervous system, the urogenital system, the digestive system and intracellular organelles.

• Digestive
• Fluorescent
• Hematopoietic
• Nervous
• Organelle
• Signal
• Skeletal
• Transgenic
• Urogenital
• Zebrafish

To meet the needs of foetal growth and development, marked changes in lipid profiles occur during pregnancy. Abnormal lipid metabolism is often accompanied by adverse pregnancy outcomes, which seriously affect maternal and infant health. Further understanding of the mechanism of lipid metabolism during pregnancy would be helpful to reduce the incidence of adverse pregnancy outcomes.

Pregnant mice were euthanized in the virgin (V) state, on day 5 of pregnancy (P5), on day 12 of pregnancy (P12), on day 19 of pregnancy (P19) and on lactation day 2 (L2). Body weight and energy expenditure were assessed to evaluate the general condition of the mice. Triglyceride (TG) levels, the cholesterol content in the liver, liver histopathology, serum lipid profiles, serum β-hydroxybutyrate levels, fibroblast growth factor-21 (FGF21) levels and the levels of relevant target genes were analysed.

During early pregnancy, anabolism was found to play a major role in liver lipid deposition. In contrast, advanced pregnancy is an overall catabolic condition associated with both increased energy expenditure and reduced lipogenesis. Moreover, the accumulation of hepatic TG did not appear until P12, after the onset of endoplasmic reticulum (ER) stress on P5. Then, catabolism was enhanced, and FGF21 secretion was increased in the livers of female mice in late pregnancy. We further found that the expression of sec23a, which as the coat protein complex II (COPII) vesicle coat proteins regulates the secretion of FGF21, in the liver was decreased on P19.

With the activation of ER stress and increased FGF21 secretion during pregnancy, the hepatic TG content changes, suggesting that ER stress and FGF21 may play an important role in balancing lipid homeostasis and meeting maternal and infant energy requirements in late pregnancy.

• Endoplasmic reticulum stress
• FGF21
• Lipid metabolism
• Pregnancy

• Acute hepatic injury
• Ethanol
• Liver
• Zebrafish

• Adverse outcome pathways
• Alkoxy alcohols
• Developmental toxicity
• Metabolism
• Zebrafish embryos

• Bisphenol S
• Long-term exposure
• Male zebrafish
• Non-alcoholic fatty liver
• Unfolded protein response

• Animals
• Endoplasmic Reticulum Stress
• Lipid Metabolism
• Liver
• Male
• Non-alcoholic Fatty Liver Disease
• Phenols
• Sulfones
• Unfolded Protein Response
• Zebrafish

• Biofuels
• Ectoine
• Entropy
• Ethanol
• Fermentation
• Urea
• Vanillin

The present work investigated the anti-inflammatory, antioxidant, and lung protection effects of acetylated Pleurotus geesteranus polysaccharides (AcPPS) on acute lung injury (ALI) mice. The acetylation of AcPPS was successfully shown by the peaks of 1737 cm⁻¹ and 1249 cm⁻¹ by FTIR. The animal experiments demonstrated that lung damage can be induced by zymosan. However, the supplementation of AcPPS had potential effects on reducing lung index, remitting inflammatory symptoms (TNF-α, IL-1β, and IL-6), inhibiting NF-κB signal pathway based on up-regulating the level of IκBα and down-regulating p-IκBα level by Western blotting and immunofluorescence assay, preventing oxidative stress (ROS, SOD, GSH-Px, CAT, T-AOC, and MDA), reducing lipid accumulation (TC, TG, LDL-C, HDL-C, and VLDL-C), and alleviating lung functions by histopathologic observation. These results demonstrated that AcPPS might be suitable for natural food for prevention or remission in ALI.

• Acetylated polysaccharides
• Acute lung injury
• Antioxidant
• Pleurotus geesteranus

Alcoholic liver disease (ALD), which is recognized as an important health problem worldwide, is a direct consequence of alcohol consumption, which can induce alcoholic fatty liver, alcoholic steatohepatitis, fibrosis and cirrhosis. P-Hydroxyacetophenone (p-HAP) is mainly used as a choleretic and hepatoprotective compound and has anti-hepatitis B, antioxidative and anti-inflammatory effects. However, no experimental report has focused on p-HAP in ALD, and the effect and mechanism of p-HAP in ALD remain unknown. In addition, there is no research on p-HAP in the treatment of ALD. The potential molecular mechanisms of p-HAP against acute alcoholic liver injury remain unknown. In this study, we aimed to investigate whether p-HAP alleviates ALD and to clarify the potential molecular mechanisms. Zebrafish larvae were soaked in 350 mmol/l ethanol for 32 h at 4 days post fertilization (dpf) and then treated with p-HAP for 48 h. We chose various outcome measures, such as liver histomorphological changes, antioxidation and antiapoptosis capability and expression of inflammation-related proteins, to elucidate the essential mechanism of p-HAP in the treatment of alcohol-induced liver damage. Subsequently, we applied pathological hematoxylin and eosin (H&E) staining, Nile red staining and oil red O staining to detect the histomorphological and lipid changes in liver tissues. We also used TUNEL staining, immunochemistry and Western blot analysis to reveal the changes in apoptosis- and inflammation-related proteins. In particular, we used a variety of fluorescent probes to detect the antioxidant capacity of p-HAP in live zebrafish larvae in vivo. In addition, we discovered that p-HAP treatment relieved alcoholic hepatic steatosis in a dose-dependent manner and that the 50 μM dose had the best therapeutic effect. Generally, this research indicated that p-HAP might reduce oxidative stress and cell apoptosis in vivo and in vitro via the NF-κB signaling pathway.

• alcoholic liver disease
• apoptosis
• oxidative stress
• p-HAP
• zebrafish larvae

• ALD
• NAFLD
• hepatocellular carcinoma
• kupffer cells
• monocytes
• regeneration

• Animals
• Disease Models, Animal
• Hematopoiesis
• Liver Diseases/immunology
• Liver Diseases, Alcoholic/immunology
• Liver Neoplasms/immunology
• Liver Regeneration
• Macrophages/physiology
• Zebrafish

• R01 DK090311 NIDDK NIH HHS
• R01 DK095721 NIDDK NIH HHS
• R01 DK117266 NIDDK NIH HHS
• R24 OD017870 NIH HHS

• CYP
• Cytochrome P450
• Liver
• Transcript expression
• Zebrafish

• Bax
• Bcl-2
• Hepatocyte apoptosis
• Liver injury
• MAPK/p53 signaling pathway
• Triclosan exposure

• Animals
• Biomarkers
• Chemical and Drug Induced Liver Injury/metabolism
• Chemical and Drug Induced Liver Injury/pathology
• Chemical and Drug Induced Liver Injury/veterinary
• Fish Diseases/chemically induced
• Gene Expression Regulation/drug effects
• Hepatocytes/drug effects
• Hepatocytes/metabolism
• Larva/drug effects
• Mitogen-Activated Protein Kinase Kinases/genetics
• Mitogen-Activated Protein Kinase Kinases/metabolism
• Triclosan/toxicity
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism
• Zebrafish

• Ethanol
• Hepatic injury
• Liver
• Steatosis
• Zebrafish

• Autophagy
• Cirrhosis
• Drug-Induced Liver Injury
• Inflammation
• Model Organisms
• Tumor Microenvironment

• Animals
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Disease Models, Animal
• Gene Regulatory Networks
• Genetic Predisposition to Disease
• Hormones/metabolism
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Mutation
• Tumor Microenvironment
• Zebrafish

• R03 DK085445 NIDDK NIH HHS
• R24 OD017870 NIH HHS
• F32 AA025271 NIAAA NIH HHS
• F32 AA027135 NIAAA NIH HHS
• R01 DK105198 NIDDK NIH HHS
• R01 DK090311 NIDDK NIH HHS

• developmental biology
• metabolomics
• non-alcoholic fatty liver disease
• obesity
• oncogenesis
• transcriptomics

• Hepatotoxicity
• Mechanisms of toxicity
• Zebrafish larvae

• Animals
• Chemical and Drug Induced Liver Injury/diagnosis
• Chemical and Drug Induced Liver Injury/genetics
• Disease Models, Animal
• Environmental Exposure/adverse effects
• Gene Expression Profiling
• Gene Expression Regulation, Developmental/drug effects
• Larva/drug effects
• Larva/growth & development
• Larva/metabolism
• Sequence Analysis, RNA
• Zebrafish

• K08 DK101340 NIDDK NIH HHS
• T32 HD049311 NICHD NIH HHS

• Animals
• Appetite/drug effects
• Appetite/physiology
• Appetite Depressants/pharmacology
• Appetite Stimulants/pharmacology
• Behavior, Animal/drug effects
• Drug Discovery
• Drug Evaluation, Preclinical
• High-Throughput Screening Assays/methods
• Male
• Mice
• Mice, Inbred C57BL
• Models, Animal
• Swimming
• Zebrafish

• R24 NS086601 NINDS NIH HHS
• R43 OD024879 NIH HHS
• T32 HL007208 NHLBI NIH HHS
• U19 NS104653 NINDS NIH HHS
• R01 MH086867 NIMH NIH HHS
• R01 GM088040 NIGMS NIH HHS

The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in vitro thus causing membrane remodeling—changes in membrane fluidity and lipid-raft characteristics. In this study, the possible involvement of membrane remodeling in the in vivo progression of steatosis to a steatohepatitis-like state upon co-exposure to B[a]P and ethanol was tested in obese zebrafish larvae. Larvae bearing steatosis as the result of a high-fat diet were exposed to ethanol and/or B[a]P for seven days at low concentrations coherent with human exposure in order to elicit hepatotoxicity. In this condition, the toxicant co-exposure raised global membrane order with higher lipid-raft clustering in the plasma membrane of liver cells, as evaluated by staining with the fluoroprobe di-4-ANEPPDHQ. Involvement of this membrane’s remodeling was finally explored by using the lipid-raft disruptor pravastatin that counteracted the effects of toxicant co-exposure both on membrane remodeling and toxicity. Overall, it can be concluded that B[a]P/ethanol co-exposure can induce in vivo hepatotoxicity via membrane remodeling which could be considered as a good target mechanism for developing combination therapy to deal with steatohepatitis.

• benzo[a]pyrene
• co-exposure
• ethanol
• high-fat diet
• lipid raft
• liver steatosis
• membrane remodeling
• pravastatin
• steatohepatitis
• zebrafish larva

• Animals
• Benzo(a)pyrene/toxicity
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/metabolism
• Chemical and Drug Induced Liver Injury/pathology
• Ethanol/toxicity
• Fatty Liver/etiology
• Fatty Liver/metabolism
• Fatty Liver/pathology
• Hepatocytes/drug effects
• Hepatocytes/pathology
• Membrane Microdomains/drug effects
• Zebrafish

The rapid increase in fatty liver disease (FLD) incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs) is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD). We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf), including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR) caused by endoplasmic reticulum (ER) stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin), suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease.

This article has an associated First Person interview with the first author of the paper.

Summary: Using zebrafish, the authors show that exposure to a common environmental contaminant, inorganic arsenic, increases the risk of alcoholic liver disease.

• Arsenic
• Environmental exposure
• Ethanol
• Fatty liver disease

The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD). Alcohol was administered to healthy female rats starting from 6% (v/v) and gradually increased to 20% (v/v) by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity). Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

Previous studies have established the anticancer effect of vitamin K2 (VK2). However, its effect on lymphoma induced by UBIAD1/heix mutation in Drosophila remains unknown. Therefore, we aimed to develop an in vivo model of lymphoma for the precise characterization of lymphoma phenotypes. We also aimed to improve the understanding of the mechanisms that underlie the preventative effects of VK2 on lymphoma. Our results demonstrated that VK2 prevents lymphoma by acting as an electron carrier and by correcting the function and structure of mitochondria by inhibiting mitochondrial reactive oxygen species production mtROS. Our work identifies mitochondria as a key player in cancer therapy strategies.

• 4-Nitrophenol
• CYP2E1
• Ethanol
• Zebrafish

• Animals
• Brain/metabolism
• Cytochrome P-450 CYP2E1
• Enzyme Induction
• Ethanol/pharmacology
• Liver/metabolism
• Male
• Microsomes, Liver/metabolism
• Mitochondria/metabolism
• Mixed Function Oxygenases/biosynthesis
• Mixed Function Oxygenases/metabolism
• Myocardium/metabolism
• Nitrophenols/metabolism
• Rats
• Zebrafish
• Zebrafish Proteins/biosynthesis
• Zebrafish Proteins/metabolism

• F32 ES027306 NIEHS NIH HHS
• P42 ES010356 NIEHS NIH HHS
• T32 ES021432 NIEHS NIH HHS

• ALD, alcoholic liver disease
• ALT, alanine aminotransferase
• ARE, antioxidant response element
• AST, aspartate aminotransferase
• Alcoholic liver injury
• CYP2E1, cytochrome P450 2E1 enzyme
• EtOH, ethanol
• GCLC, glutamate–cysteine ligase catalytic subunit
• GCLM, glutamate–cysteine ligase modifier subunit
• GSH, glutathione
• H&E, hematoxylin and eosin
• HO-1, heme oxygenase-1
• NRF2, nuclear factor erythroid 2-related factor 2
• NRF2-ARE
• Oxidative stress
• SOD, superoxide dismutase
• Schisandra sphenanthera
• WZ, Wuzhi Tablet.
• Wuzhi Tablet

• developmental biology
• issue 123
• histology
• alcoholic liver disease
• animal model
• hepatology
• steatosis
• hematoxylin
• eosin

• Animals
• Blood Vessels/pathology
• Coloring Agents
• Eosine Yellowish-(YS)
• Ethanol/toxicity
• Fatty Liver, Alcoholic/pathology
• Fatty Liver, Alcoholic/veterinary
• Fibrosis
• Hematoxylin
• Histological Techniques
• Larva
• Liver/blood supply
• Liver/drug effects
• Liver/pathology
• Zebrafish

• P30 DK078392 NIDDK NIH HHS
• R00 AA020514 NIAAA NIH HHS

Alcoholic liver disease (ALD) is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP) zebrafish larvae (4 dpf). The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1). In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism.

• Alcoholic liver disease
• Cholestasis
• Fibrosis
• Liver regeneration
• Non-alcoholic fatty liver disease
• Steatosis

• ZeGlobalTox
• adverse drug reaction
• cardiotoxicity
• drug toxicity
• hepatotoxicity
• high-throughput
• neurotoxicity
• zebrafish

• Animals
• Cardiotoxicity
• Drug Evaluation, Preclinical/methods
• Drug-Related Side Effects and Adverse Reactions
• Liver/drug effects
• Liver/pathology
• Locomotion/drug effects
• Models, Animal
• Organ Specificity/drug effects
• Toxicity Tests
• Toxicity Tests, Acute
• Zebrafish

To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genes in zebrafish.

Zebrafish (n = 104), wild type, adult, male and female, were divided into two groups: Control and ethanol (0.05 v/v). The ethanol was directly added into water; tanks water were changed every two days and the ethanol replaced. The animals were fed twice a day with fish food until satiety. After two and four weeks of trial, livers were dissected, histological analysis (hematoxilin-eosin and Oil Red staining) and gene expression assessment of adiponectin, adiponectin receptor 2 (adipor2), sirtuin-1 (sirt-1), tumor necrosis factor-alpha (tnf-a), interleukin-1b (il-1b) and interleukin-10 (il-10) were performed. Ultrastructural evaluations were conducted at fourth week.

Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks, as demonstrated by oil red staining. In ethanol-treated animals, the main ultrastructural changes were related to cytoplasmic lipid particles and droplets, increased number of rough endoplasmic reticulum cisterns and glycogen particles. Between two and four weeks, hepatic mRNA expression of il-1b, sirt-1 and adipor2 were upregulated, indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses. Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol, and il-10 did not show significant difference.

Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

• Ethanol
• Hepatic steatosis
• Inflammation
• Zebrafish
• Alcoholic fatty liver

• Saccharomyces
• UPR
• ethanol stress
• signaling
• yeasts

• chemical agents
• hepatotoxicity
• in vivo model
• membrane remodeling
• zebrafish larva