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1.
Food Chem ; 336: 127729, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768914

RESUMO

The roles of lipid oxidation substrates and muscle microstructure in lipid oxidation were investigated in two muscle models (cod and pig). Added myoglobin (Mb) promoted lipid oxidation in washed cod muscle (WCM) but not in washed pig muscle (WPM). The differing microstructure of WCM e.g. more exposed fat cells or membrane of muscle cells compared to the "denseness" or "wrapped" structure of WPM, may have contributed to the better ability of Mb to facilitate lipid oxidation in the WCM. Added phospholipids with polyenoic indexes of 282 and 24 activated Mb as an oxidant similarly in WPM while added neutral lipids and added free fatty acids had little effect. It is suggested that muscle microstructure and accessibility of Mb to phospholipids play critical roles in relation to Mb-mediated lipid oxidation while the degree of unsaturation in the phospholipids was less important.


Assuntos
Gadiformes/metabolismo , Lipídeos/química , Músculos/metabolismo , Mioglobina/química , Animais , Cromatografia Gasosa , Peroxidação de Lipídeos , Lipídeos/análise , Suínos , alfa-Tocoferol/análise
2.
Nat Commun ; 11(1): 5432, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116134

RESUMO

Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, we create three independent libraries comprising 183 different AAV variants including widely used benchmarks and screened them in all major tissues in adult mice. Thereby, we discover a peptide-displaying AAV9 mutant called AAVMYO that exhibits superior efficiency and specificity in the musculature including skeletal muscle, heart and diaphragm following peripheral delivery, and that holds great potential for muscle gene therapy. Our comprehensive methodology is compatible with any capsids, targets and species, and will thus facilitate and accelerate the stratification of optimal AAV vectors for human gene therapy.


Assuntos
Proteínas do Capsídeo/genética , Dependovirus/genética , Vetores Genéticos , Músculos/metabolismo , Músculos/virologia , Animais , Capsídeo , Código de Barras de DNA Taxonômico , Feminino , Biblioteca Gênica , Terapia Genética/métodos , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Especificidade de Órgãos
3.
PLoS One ; 15(9): e0238208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881928

RESUMO

INTRODUCTION: Peripheral nerve injury (PNI) often leads to significant functional loss in patients and poses a challenge to physicians since treatment options for improving functional outcomes are limited. Recent studies suggest that erythropoietin and glucocoticoids have beneficial effects as mediators of neuro-regenerative processes. We hypothesized that combination treatment with erythropoietin and glucocoticoids would have a synergistic effect on functional outcome after PNI. MATERIALS AND METHODS: Sciatic nerve crush injury was simulated in ten-week-old male C57BL/6 mice. The mice were divided into four groups according to the type of drugs administered (control, erythropoietin, dexamethasone, and erythropoietin with dexamethasone). Motor functional recovery was monitored by walking track analysis at serial time points up to 28 days after injury. Morphological analysis of the nerve was performed by immunofluorescent staining for neurofilament (NF) heavy chain and myelin protein zero (P0) in cross-sectional and whole-mount nerve preparations. Additionally, morphological analysis of the muscle was performed by Hematoxylin and eosin staining. RESULTS: Combination treatment with erythropoietin and dexamethasone significantly improved the sciatic functional index at 3, 7, 14, and 28 days after injury. Fluorescence microscopy of cross sectional nerve revealed that the combination treatment increased the ratio of P0/NF-expressing axons. Furthermore, confocal microscopy of the whole-mount nerve revealed that the combination treatment increased the fluorescence intensity of P0 expression. The cross-sectional area and minimum Feret's diameter of the muscle fibers were significantly larger in the mice which received combination treatment than those in the controls. CONCLUSION: Our results demonstrated that combination treatment with erythropoietin and dexamethasone accelerates functional recovery and reduces neurogenic muscle atrophy caused by PNI in mice, which may be attributed to the preservation of myelin and Schwann cell re-myelination. These findings may provide practical therapeutic options for patients with acute PNI.


Assuntos
Dexametasona/uso terapêutico , Eritropoetina/uso terapêutico , Músculos/metabolismo , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/metabolismo , Doença Aguda , Animais , Axônios/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Eritropoetina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Músculos/patologia , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Proteína P0 da Mielina/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Células de Schwann/citologia , Células de Schwann/metabolismo , Nervo Isquiático/patologia
4.
PLoS One ; 15(9): e0239358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970715

RESUMO

There is an extensive literature establishing, validating, and quantifying a wide range of responses of fishes to fasting. Our study complements this work by comparing fed and unfed treatments of hatchery-raised Delta Smelt (Hypomesus transpacificus)-an imperiled fish that is endemic to the San Francisco Estuary and its tributaries in California, USA-across a diverse suite of endpoints over a two-month time series. The experiment was conducted at 15.9°C, and individuals were sampled at 12 time points as starvation became increasingly severe. We found that hepatosomatic index and condition factor were relatively sensitive to starvation, becoming significantly depressed at Day 4 and 7, respectively. Histological analysis of liver showed elevated cytoplasmic inclusion bodies at Day 7, followed by increased glycogen depletion, single cell necrosis, and hydropic vacuolar degeneration at Day 14, 21, and 28, respectively. Of four antioxidants measured, glutathione decreased at Day 4, superoxide dismutase increased at Day 14, catalase increased at Day 56, and glutathione peroxidase was not affected by starvation. The net result was a ~2-fold increase in lipid peroxidation (malondialdehyde) in fasted fish that was highly inconsistent through time. RNA to DNA ratio and triglycerides in muscle were relatively insensitive to starvation, only consistently decreasing with fasting after mortality began increasing in the 'No Feeding' treatment, at Day 21. Together, these results suggest that Delta Smelt mobilize hepatic energy stores far more rapidly than lipids in muscle when subjected to fasting, leading to rapid atrophy of liver and the development of cytoplasmic inclusion bodies-possibly autophagosomes-in hepatocytes.


Assuntos
Osmeriformes/metabolismo , Inanição , Animais , Catalase/metabolismo , Glutationa/metabolismo , Glicogênio/metabolismo , Corpos de Inclusão/metabolismo , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Músculos/metabolismo , Músculos/patologia , Necrose , Osmeriformes/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo , Fatores de Tempo
5.
PLoS One ; 15(9): e0239143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941478

RESUMO

Feed efficiency (FE) is a key trait in pig production, as improvement in FE has positive economic and environmental impact. FE is a complex phenotype and testing animals for FE is costly. Therefore, there has been a desire to find functionally relevant single nucleotide polymorphisms (SNPs) as biomarkers, to improve our biological understanding of FE as well as accuracy of genomic prediction for FE. We have performed a cis- and trans- eQTL (expression quantitative trait loci) analysis, in a population of Danbred Durocs (N = 11) and Danbred Landrace (N = 27) using both a linear and ANOVA model based on muscle tissue RNA-seq. We analyzed a total of 1425x19179 or 2.7x107 Gene-SNP combinations in eQTL detection models for FE. The 1425 genes were from RNA-Seq based differential gene expression analyses using 25880 genes related to FE and additionally combined with mitochondrial genes. The 19179 SNPs were from applying stringent quality control and linkage disequilibrium filtering on genotype data using a GGP Porcine HD 70k SNP array. We applied 1000 fold bootstrapping and enrichment analysis to further validate and analyze our detected eQTLs. We identified 13 eQTLs with FDR < 0.1, affecting several genes found in previous studies of commercial pig breeds. Examples include MYO19, CPT1B, ACSL1, IER5L, CPT1A, SUCLA2, CSRNP1, PARK7 and MFF. The bootstrapping results showed statistically significant enrichment (p-value<2.2x10-16) of eQTLs with p-value < 0.01 in both cis and trans-eQTLs. Enrichment analysis of top trans-eQTLs revealed high enrichment for gene categories and gene ontologies associated with genomic context and expression regulation. This included transcription factors (p-value = 1.0x10-13), DNA-binding (GO:0003677, p-value = 8.9x10-14), DNA-binding transcription factor activity (GO:0003700,) nucleus gene (GO:0005634, p-value<2.2x10-16), negative regulation of expression (GO:0010629, p-value<2.2x10-16). These results would be useful for future genome assisted breeding of pigs to improve FE, and in the improved understanding of the functional mechanism of trans eQTLs.


Assuntos
Cruzamento , Locos de Características Quantitativas , Sus scrofa/genética , Transcriptoma , Criação de Animais Domésticos , Animais , Dinamarca , Genes Mitocondriais , Masculino , Músculos/metabolismo , Polimorfismo de Nucleotídeo Único
6.
PLoS One ; 15(9): e0239467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970731

RESUMO

Dystrophin plays a vital role in maintaining muscle health, yet low mRNA expression, lengthy transcription time and the limitations of traditional in-situ hybridization (ISH) methodologies mean that the dynamics of dystrophin transcription remain poorly understood. RNAscope is highly sensitive ISH method that can be multiplexed, allowing detection of individual transcript molecules at sub-cellular resolution, with different target mRNAs assigned to distinct fluorophores. We instead multiplex within a single transcript, using probes targeted to the 5' and 3' regions of muscle dystrophin mRNA. Our approach shows this method can reveal transcriptional dynamics in health and disease, resolving both nascent myonuclear transcripts and exported mature mRNAs in quantitative fashion (with the latter absent in dystrophic muscle, yet restored following therapeutic intervention). We show that even in healthy muscle, immature dystrophin mRNA predominates (60-80% of total), with the surprising implication that the half-life of a mature transcript is markedly shorter than the time invested in transcription: at the transcript level, supply may exceed demand. Our findings provide unique spatiotemporal insight into the behaviour of this long transcript (with implications for therapeutic approaches), and further suggest this modified multiplex ISH approach is well-suited to long genes, offering a highly tractable means to reveal complex transcriptional dynamics.


Assuntos
Distrofina/genética , Expressão Gênica/genética , Hibridização In Situ/métodos , Animais , Distrofina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Multiplex/métodos , Músculos/metabolismo , RNA Mensageiro/genética , Transcrição Genética/genética
7.
PLoS One ; 15(8): e0231364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804943

RESUMO

Phosphoinositides (PIPs) and their regulatory enzymes are key players in many cellular processes and are required for aspects of vertebrate development. Dysregulated PIP metabolism has been implicated in several human diseases, including a subset of skeletal myopathies that feature structural defects in the triad. The role of PIPs in skeletal muscle formation, and particularly triad biogenesis, has yet to be determined. CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) catalyzes the formation of phosphatidylinositol, which is the base of all PIP species. Loss of CDIPT should, in theory, result in the failure to produce PIPs, and thus provide a strategy for establishing the requirement for PIPs during embryogenesis. In this study, we generated cdipt mutant zebrafish and determined the impact on skeletal myogenesis. Analysis of cdipt mutant muscle revealed no apparent global effect on early muscle development. However, small but significant defects were observed in triad size, with T-tubule area, inter terminal cisternae distance and gap width being smaller in cdipt mutants. This was associated with a decrease in motor performance. Overall, these data suggest that myogenesis in zebrafish does not require de novo PIP synthesis but does implicate a role for CDIPT in triad formation.


Assuntos
CDP-Diacilglicerol-Inositol 3-Fosfatidiltransferase/metabolismo , Fosfatidilinositóis/biossíntese , Fosfatidilinositóis/metabolismo , Animais , CDP-Diacilglicerol-Inositol 3-Fosfatidiltransferase/biossíntese , Fosfatos de Inositol/metabolismo , Lipogênese , Desenvolvimento Muscular/genética , Músculos/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
8.
Ecotoxicol Environ Saf ; 205: 111127, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32846293

RESUMO

Trichlorfon is an organophosphate insecticide that is widely used on fish farms to control parasitic infections. It has been detected in freshwater ecosystems as well as in fishery products. There is a growing body of evidence to suggest that certain feed additives may reduce or prevent pesticide-induced toxicity in fish. The aim of the present study was to determine whether acute exposure to trichlorfon would alter bioenergetic homeostasis and alter fatty acid profiles in muscles of silver catfish (Rhamdia quelen). We also sought to determine whether rutin prevents or reduces these effects. Cytosolic and mitochondrial creatine kinase (CK) and activities of complexes II-III and IV in muscle were significantly inhibited by exposure to 11 mg/L trichlorfon for 48 h compared to effects in the unexposed group. Total content of polyunsaturated fatty acids (omega-3 and omega-6) were significantly lower in muscle of silver catfish exposed to 11 mg/L trichlorfon for 48 h than in the unexposed group. Addition of 3 mg rutin/kg feed increased CK activity and prevented inhibition of complex IV activity, as well as preventing all alterations of muscle fatty acid profiles elicited by exposure to trichlorfon. No significant differences were observed between groups with respect to muscle adenylate kinase or pyruvate kinase activities, as well as total content of saturated and monounsaturated fatty acids. Our findings suggest that exposure (48 h) to 11 mg trichlorfon/L water inhibits cytosolic and mitochondrial CK activity in muscle. Trichlorfon also affects activities of complexes II-III and IV in respiratory chain, with important consequences for adenosine triphosphate production. The pesticide alters fatty acid profiles in the fish and endangers human consumers of the product. The most important finding of the present study is that inclusion of rutin improves bioenergetic homeostasis and muscle fatty acid profiles, suggesting that it reduces trichlorfon-induced muscle damage.


Assuntos
Peixes-Gato/metabolismo , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Inseticidas/toxicidade , Músculos/efeitos dos fármacos , Rutina/farmacologia , Triclorfon/toxicidade , Trifosfato de Adenosina/metabolismo , Adenilato Quinase/metabolismo , Ração Animal , Animais , Peixes-Gato/crescimento & desenvolvimento , Creatina Quinase/metabolismo , Dieta , Aditivos Alimentares , Homeostase , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Músculos/metabolismo
9.
J Chromatogr A ; 1626: 461311, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797814

RESUMO

Comprehensive two-dimensional gas chromatography (GC×GC) is a powerful tool for complex separations. The selectivity and sensitivity benefits from thermally modulated GC×GC were applied to the analysis of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Thermodynamic indices of 50 PCDD/Fs, including the 17 toxic 2378-substituted congeners, were collected and used to model one-dimensional and two-dimensional separations with the Rtx-Dioxin2 and Rxi-17SilMS capillary GC columns. Thermodynamic modeling was used to determine the optimal conditions to take advantage of the selectivity differences between the Rxi-17SilMS and Rtx-Dioxin2 to separate all PCDD/Fs congeners from the 2378-substituted compounds by GC×GC. The modeled elution order patterns closely matched the experimental elution order in 40 of the 45 tetrachlorinated through hexchlorinated compounds analyzed. The heptachlorinated and octachlorinated congeners were not included in the elution order modeling as they are readily resolved from other dioxin congeners. The Rxi-17SilMS crossed with the Rtx-Dioxin2 was able to separate all 2378-substituted compounds in a single separation in a fish matrix. Thirty-three additional PCDD/F congeners were added to the fish matrix that coelute with the 2378-substituted congeners. The Rxi-17SilMS crossed with the Rtx-Dioxin2 was able to fully resolve 11 of the 2378-substituted congeners with the other six congeners exhibiting coelutions with only one other congener.


Assuntos
Cromatografia Gasosa/métodos , Dibenzofuranos Policlorados/análise , Músculos/química , Dibenzodioxinas Policloradas/análise , Animais , Monitoramento Ambiental , Peixes/metabolismo , Músculos/metabolismo , Termodinâmica
10.
Ecotoxicol Environ Saf ; 202: 110954, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800228

RESUMO

Current study aims to determine difference in metal accumulation pattern in muscle of Liza parsia (pelagic, omnivore), Amblypharyngodon mola (surface feeder, herbivore) and Mystus gulio (benthic, carnivore) depending on their niche and feeding habit and how it affects the endogenous antioxidants and glucose metabolism in fish muscle. Fishes were collected from Malancha, Diamond Harbour and Chandanpiri, West Bengal, India. Concentrations of lead, zinc, cadmium, chromium were measured in water, sediment and fish muscle. Metal pollution index (MPI) and bioconcentration factor (BCF) was calculated to evaluate the ability of fish to accumulate specific metals in muscle tissue from the aquatic environment. Metal concentrations were found significantly higher (P < 0.05) in water, sediment, fish muscles from Malancha than Chandanpiri and Diamond Harbour. L. parsia (MPI: 0.4-1.6) showed highest metal deposition in their muscle followed by A. mola (MPI: 0.37-1.38) and M. gulio (MPI: 0.2-1.2). Malondealdehyde, superoxide dismutase, catalase, glutathione S transferase, glutathione reductase and cortisol levels increased in case of L. parsia from Malancha and Chandanpiri. Succinate dehydrogenase, lactate dehydrogenase, Ca+2 ATPase and cytochrome C oxidase levels were significantly (P < 0.05) lower at Malancha and Chandanpiri than Diamond Harbour. Heat shock protein (HSP70) expression was significantly (P < 0.05) higher in all fish species at Malancha followed by Chandanpiri and Diamond Harbour. Glucose, glycogen, hexokinase, phosphofructokinase and glycogen phosphorylase levels varied between sites and selected fish species. Serum cortisol level was measured and found to be the highest in L. parsia from Malancha (2.94 ± 0.12 ng/ml) and the lowest in M. gulio from Diamond Harbour (0.7 ± 0.05 ng/ml). The results indicate that metal toxicity alters antioxidant levels, oxidative status and energy production in fish in species specific manner. Our results also indicate that Mystus has the highest degree of adaptability in response to metal toxicity possibly due to its specific food habit and niche position. Therefore, it can be concluded that maintenance of oxidative and metabolic status to combat metal-induced oxidative load will be helpful for the fishes to acquire better resistance under such eco-physiological stress. Alteration of niche and interactive segregation in aquatic organism may be one of the key modulator of resistance against such stress.


Assuntos
Antioxidantes/metabolismo , Cyprinidae/metabolismo , Comportamento Alimentar/fisiologia , Glucose/metabolismo , Metais Pesados/toxicidade , Músculos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Cyprinidae/fisiologia , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Índia , Metais Pesados/metabolismo , Músculos/enzimologia , Músculos/metabolismo , Oxirredução , Especificidade da Espécie , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo
11.
Gene ; 758: 144986, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32711100

RESUMO

Myostatin (Mstn) inhibits muscle growth in vertebrates with endoskeleton, but it is still inconclusive that Mstn is a positive or negative regulator in crustacean with exoskeleton, and little information was available for its function on myogenesis. In this study, we identified and characterized the Mstn from Fenneropenaeus chinensis (FcMstn), and investigated its function on myogenesis and muscle growth. Two different cDNA sequences (2628 bp and 2604 bp) encoding for slightly different sizes of proteins were obtained for FcMstn, containing 86 bp of 5' untranslated regions (UTR) and 1258 bp of 3' UTR. The open reading frame of the long sequence and the short sequence contain 1284 bp and 1260 bp cDNA, encoding 427 and 419 amino acid sequence, respectively. Sequence analysis revealed that the overall protein sequence and specific functional sites of FcMstn were highly conserved with those in other crustacean species. In the early development stage, the muscle firstly appeared in nauplius stage and developed gradually until post larval, but the expression of FcMstn at mRNA and protein levels decreased from nauplius stage to post larval stage, indicating that Mstn involved in myogenesis as a negative regulator in shrimp. In the adult shrimp, the expression of FcMstn at mRNA and protein levels in muscle were significantly lower in the larger group than in the smaller group, and the diameter and number of muscle fiber of the muscle were significantly different between the two groups. Moreover, the shrimp with reduced level of FcMstn by RNAi displayed a dramatic faster growth rate compared with the control group. The present study demonstrates that FcMstn involved in myogenesis and muscle growth probably also as a negative regulator in shrimp like in vertebrates.


Assuntos
Desenvolvimento Muscular/genética , Músculos/metabolismo , Miostatina/genética , Miostatina/metabolismo , Penaeidae/genética , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Perfilação da Expressão Gênica , Fases de Leitura Aberta/genética , Filogenia , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Alinhamento de Sequência
12.
Chemosphere ; 257: 127183, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32497841

RESUMO

Here, we evaluate maternal offloading of 16 trace elements (Essential: Co, Cr, Cu, Fe, Mn, Ni, Se and Zn; Nonessential: Al, As, Ba, Cd, Hg, Pb, Tl and U) and determine mother-offspring isotopic fractionation of δ13C and δ15N in muscle and liver tissue of four pregnant Mustelus higmani and 18 associated embryos sampled from the Amazon Coast of Brazil. Embryo muscle tissue had significantly higher concentrations of most trace elements when compared to mothers, with the exception of Hg. Embryo liver accumulated more nonessential elements than muscle (n = 7 vs. 0, respectively), while the Se:Hg molar ratio was >1 in liver and muscle of both mothers and embryos. Livers of embryos were moderately enriched in δ13C and δ15N when compared to that of their mother. Negative correlations were observed between embryo body length and δ13C and trace elements concentrations. We conclude that mothers offload a large portion of all essential elements and Al, As and Pb to their young and that the isotopic fractionation of embryos reflects maternal diet and habitat occupied, with δ13C diluted with embryonic growth. We also show that muscle and liver accumulate trace elements at different rates relative to the body length of embryos. The Se:Hg molar ratio suggests that Se could play a protective role against Hg toxicity during early stages of M. higmani embryonic development.


Assuntos
Monitoramento Ambiental , Músculos/metabolismo , Tubarões/metabolismo , Oligoelementos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Brasil , Ecossistema , Feminino , Isótopos , Fígado/química , Mercúrio , Músculos/química , Gravidez , Oligoelementos/análise
13.
PLoS One ; 15(6): e0234571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525922

RESUMO

Metformin, an anti-diabetes drug, has been recently emerging as a potential "anti-aging" intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while, ~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at ~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state metformin levels in plasma, liver, muscle, kidney, and brain of normoglycemic mice treated with a clinically relevant dose, providing insight into future metformin preclinical studies for potential clinical translation.


Assuntos
Metformina/farmacocinética , Animais , Encéfalo/metabolismo , Cromatografia Líquida , Feminino , Rim/metabolismo , Fígado/metabolismo , Masculino , Metformina/administração & dosagem , Metformina/sangue , Camundongos , Camundongos Endogâmicos C57BL , Músculos/metabolismo , Espectrometria de Massas em Tandem , Distribuição Tecidual
14.
J Environ Sci Health B ; 55(8): 749-755, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558613

RESUMO

This study assessed the hematological, enzymatic and osmoregulatory responses of silver catfish (Rhamdia quelen) exposed to sublethal concentrations (1.125 and 3.750 µg/L) of a commercial thiamethoxam-containing insecticide used on rice crops. Groups of 6 fish per tank (in triplicate, n = 3, total 54 fish) were exposed for up to 96 h to different concentrations of the compound. After this period, fish were placed in clean water for 48 h. Two fish from each tank (6 per treatment) that had been exposed to the insecticide for 24 h were anesthetized with eugenol and blood was collected to evaluate hematological and biochemical parameters. Blood, liver and muscle were collected for determination of metabolic parameters, plasma cortisol, Cl-, Na+ and K+ levels and H+-ATPase and Na+/K+-ATPase activity in the gill. H+-ATPase activity was higher in fish exposed to 1.125 µg/L insecticide at 24 h compared to control (0.0 µg/L). Differences in cortisol levels were evidenced throughout the experimental period. These results indicated that exposure to the insecticide changed the hematological, biochemical and metabolic profile of the animals, suggesting concern about environmental safety. Therefore, we discourage the use of this pesticide in areas that come into contact with water bodies inhabited by fish.


Assuntos
Peixes-Gato/fisiologia , Inseticidas/toxicidade , Tiametoxam/toxicidade , Adenosina Trifosfatases/metabolismo , Animais , Peixes-Gato/sangue , Ecotoxicologia/métodos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hidrocortisona/sangue , Fígado/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Testes de Toxicidade Aguda , Poluentes Químicos da Água/toxicidade
15.
Bull Environ Contam Toxicol ; 104(6): 763-769, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32356000

RESUMO

The lower Melet River is a drinking water source that is surrounded by hazelnut grove, agricultural lands, resulting in the accumulation of genotoxic agents such as mining activities, various domestic and agricultural wastes. Therefore, it receives many domestic and agricultural wastes that contain the genotoxic agent. This study was aimed to assess the heavy metal concentrations in water, sediment, and bioaccumulation in the tissues of Alburnus chalcoides. Comet assay and micronucleus test were used to evaluate the genotoxic effects on the blood cells of A. chalcoides. The concentrations of heavy metals and metalloid in the water, in the sediments and in the muscle of fish were in the order of Fe > Al > Mn > As > Zn > Cu > Ni > Cr > Cd = Pb = Co, Fe > Al > Mn > Zn > Cu > Pb > Cr > As > Co > Ni > Cd and Fe > Zn > Al > Mn > Cu > Pb > As > Cr > Ni > Co > Cd, respectively. The blood cells of fish collected from the polluted location showed significantly higher DNA damage and micronucleus frequency compared to the reference location (p < 0.05). The study indicated that the DNA integrity of A. chalcoides was affected by heavy metals which originated from many anthropogenic sources.


Assuntos
Cyprinidae/genética , Dano ao DNA , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Agricultura , Animais , Bioacumulação/efeitos dos fármacos , Ensaio Cometa , Cyprinidae/metabolismo , Sedimentos Geológicos/química , Metais Pesados/análise , Mineração , Músculos/efeitos dos fármacos , Músculos/metabolismo , Rios/química , Turquia , Poluentes Químicos da Água/análise
16.
Chemosphere ; 255: 126941, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32388259

RESUMO

With the aim of evaluating health risk to hake consumers, mercury and selenium were measured in muscle, liver, gonads, kidney, and gills of 62 specimens of Merluccius productus from northern Gulf of California. Means ± confidence interval (95% confidence level) concentrations (mg kg-1 wet weight) of Hg in tissues were: gonads (1.01 ± 0.25) > muscle (0.44 ± 0.06) > gills (0.29 ± 0.04) > kidneys (0.20 ± 0.07) > liver (0.02 ± 0.004). No significant differences between sexes were found for Hg. The distribution of mean concentrations of Se (mg kg-1 wet weight) were: kidneys (4.61 ± 1.27) > liver (1.66 ± 0.22) > gonads (1.66 ± 0.75) > gills (0.86 ± 0.04) > muscle (0.40 ± 0.09). Se in gonads showed a significant difference between sex (females > males). Positive significant correlations with total length (p < 0.05) and total weight (p < 0.05) were found in the same tissue for both morphological variables: Hg in muscle, Se in muscle and Se in liver. An excess of Se over Hg (molar ratio Se:Hg > 1) was found in all tissues. The Hazard Quotient health risk index was evaluated for humans that consume muscle and gonads. The recommended Hg safe intake for adults and children were 110.0 and 33.0 g week-1, respectively for muscle; for gonads weekly consumption portions of 35.0 and 14.0 g for adults and children represent no Hg risk. There was no risk of exposure to Se.


Assuntos
Monitoramento Ambiental , Gadiformes/metabolismo , Mercúrio/metabolismo , Selênio/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Bioacumulação , California , Criança , Exposição Dietética/estatística & dados numéricos , Feminino , Peixes , Gônadas , Humanos , Masculino , Mercúrio/análise , Músculos/metabolismo , Perciformes , Medição de Risco , Selênio/análise , Poluentes Químicos da Água/análise
17.
Aquat Toxicol ; 223: 105482, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371337

RESUMO

The use of online remote control for 24/7 behavioural monitoring can play a key role in estimating the environmental status of aquatic ecosystems. Recording the valve activity of bivalve molluscs is a relevant approach in this context. However, a clear understanding of the underlying disturbances associated with behaviour is a key step. In this work, we studied freshwater Asian clams after exposure to crude oil (measured concentration, 167 ± 28 µg·L-1) for three days in a semi-natural environment using outdoor artificial streams. Three complementary approaches to assess and explore disturbances were used: behaviour by high frequency non-invasive (HFNI) valvometry, tissue contamination with polycyclic aromatic hydrocarbons (PAH), and proteomic analysis. Two tissues were targeted: the pool adductor muscles - retractor pedal muscle - cerebral and visceral ganglia, which is the effector of any valve movement and the gills, which are on the frontline during contamination. The behavioural response was marked by an increase in valve closure-duration, a decrease in valve opening-amplitude and an increase in valve agitation index during opening periods. There was no significant PAH accumulation in the muscle plus nervous ganglia pool, contrary to the situation in the gills, although the latter remained in the low range of data available in literature. Major proteomic changes included (i) a slowdown in metabolic and/or cellular processes in muscles plus ganglia pool associated with minor toxicological effect and (ii) an increase of metabolic and/or cellular processes in gills associated with a greater toxicological effect. The nature of the proteomic changes is discussed in terms of unequal PAH distribution and allows to propose a set of explanatory mechanisms to associate behaviour to underlying physiological changes following oil exposure. First, the first tissues facing contaminated water are the inhalant siphon, the mantle edge and the gills. The routine nervous activity in the visceral ganglia should be modified by nervous information originating from these tissues. Second, the nervous activity in the visceral ganglia could be modified by its own specific contamination. Third, a decrease in nervous activity of the cerebral ganglia close to the mouth, including some kind of narcosis, could contribute to a decrease in visceral ganglia activity via a decrease or blockage of the downward neuromodulation by the cerebro-visceral connective. This whole set of events can explain the decrease of metabolic activity in the adductor muscles, contribute to initiate the catch mechanism and then deeply modify the valve behaviour.


Assuntos
Comportamento Animal/efeitos dos fármacos , Corbicula/efeitos dos fármacos , Corbicula/metabolismo , Petróleo/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Proteoma/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Ecossistema , Água Doce/química , Gânglios/efeitos dos fármacos , Gânglios/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Proteômica
18.
PLoS One ; 15(5): e0233636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442227

RESUMO

This study assesses the respiratory dynamics related to stress parameters and resting time before slaughter, in the quality of surubim (Pseudopatystoma spp.) fillets. A completely randomized design was conducted using five treatments: resting time before slaughter of 0, 2, 4, 8 and 24 hours, with 15 fish sampled per treatment. Time 0 corresponded to the treatment without resting time, where the fish were slaughtered immediately after arriving at the processing plant. The resting time did not affect the electrolyte balance, hemoglobin, plasma, hepatic glycogen, myofibrillar fragmentation index (MFI) and water holding capacity (WHC) of surubins. However, with increased resting time, there was a significant decrease in muscle glycogen and an increase in blood pH and blood bicarbonate levels. Additionally, respiratory parameters showed an increase in pO2 and, consequently, in O2 saturation and a decrease in pCO2.The hematocrit and MCV values of the surubins after 24 hours of resting decreased significantly. In the first hours of resting, the highest values of erythrocytes and CHCM were observed. The lowest level of stress was observed for fish having 24 hours of resting. Fish having longer resting periods (8 and 24 hours) presented fillets with a higher pH (P <0.05) and the rigor mortis establishment time was shorter for the first 2 hours and 24 hours of resting time. There was a linear decrease in fillet lightness and an increase in the intensity of red (CIE a*) color up to 24 hours when resting was increased. In CIE b*, a linear decrease (P <0.05) of the yellow intensity of the fillets was observed as the surubim resting time increased. A resting time of 4 to 8 hours before slaughter is effective in reestablishing homeostasis after transporting surubim, providing fillets with higher quality and a greater length of the pre-rigor mortis period.


Assuntos
Peixes-Gato/metabolismo , Manipulação de Alimentos , Qualidade dos Alimentos , Alimentos Marinhos/análise , Animais , Cor , Homeostase , Concentração de Íons de Hidrogênio , Músculos/metabolismo , Descanso , Rigor Mortis
19.
Gene ; 752: 144782, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32442577

RESUMO

The branched-chain amino acids (BCAA) play an important role in muscle energy metabolism, and Krüppel-like factor 15 (KLF15) is an essential regulator of BCAA metabolism in muscle under nutritional deficiency. In this study, we analyzed the effect of normal feeding (starvation for 0 day), starvation for 3, 7, 10, 15 days, and refeeding for 7 days after 15 days of starvation on the expression of KLF15 and BCAA metabolism in muscle of Chinese soft-shelled turtles by a fasting-refeeding trial. The results showed that the level of KLF15 transcription was increased first and then decreased in muscle during short-term starvation, and the protein level was gradually increased. Both the mRNA and protein level of the KLF15 returned to normal feeding level after refeeding for 7 days. The changing trend of the activities of branched-chain aminotransferase (BCAT) and alanine aminotransferase (ALT) was consistent to that of KLF15 mRNA, but at the transcription level, the expression of BCAT mRNA was consistent with the change of enzyme activity as well as ALT continued to increase in muscle under starvation. In addition, BCAA content showed a trend that decreased first and then increased under starvation, while the alanine (Ala) was the contrary. The above results indicated that the regulatory role of KLF15 in BCAA catabolism of muscle in Chinese soft-shelled turtles under nutritional deficiency, which might be activated the catabolism of BCAA in muscle to provide energy and maintain the homeostasis by KLF15-BACC signaling axis.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Músculo Esquelético/metabolismo , Alanina Transaminase/metabolismo , Aminoácidos de Cadeia Ramificada/genética , Animais , Metabolismo Energético/fisiologia , Jejum , Fatores de Transcrição Kruppel-Like/genética , Músculos/metabolismo , Transdução de Sinais/fisiologia , Inanição/metabolismo , Tartarugas/genética , Tartarugas/metabolismo
20.
Chemosphere ; 256: 127134, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32460163

RESUMO

This study assesses arsenic (As) fractionation in sediments and speciation in muscle tissues of Bagrid catfish, Chrysichthys nigrodigitatus from Lagos Lagoon, southwest Nigeria to determine risks to ecological receptors and humans. Residual As was the predominant geochemical fraction (86.2%) in sediments. Arsenite [As (III)] concentrations which ranged from 0.06 to 0.53 mg kg-1 in catfish muscle tissue, accounting for 25.9% of total As was the dominant species. Less toxic dimethylarsinic acid (DMA) which varied between 0.06 and 0.27 mg kg-1 made up to 10.8% of total As in catfish muscle tissue. Estimated human average daily intake (ADI) of As as As (III) and DMA were 1.35 × 10-4 and 0.62 × 10-4 mg kg-1 BW with corresponding hazard quotients (HQs) of 0.45 and 0.21, respectively, indicate no apparent health hazard to adult consumers. The incremental lifetime cancer risks (ILCR) of 0.78 × 10-3 for total As, 0.20 × 10-3 for As (III), and 0.93 × 10-3 for DMA, for adults from the consumption of catfish is slightly higher than the US EPA threshold and indicates moderate carcinogenic risk. Furthermore, 12.5% bioavailable fraction of As in sediment and relatively higher levels of As (III) in fish tissues has ecological and public health implications.


Assuntos
Arsênico/análise , Ácido Cacodílico/análise , Peixes-Gato/metabolismo , Sedimentos Geológicos/química , Músculos/metabolismo , Poluentes Químicos da Água/análise , Adulto , Animais , Arsênico/metabolismo , Ácido Cacodílico/metabolismo , Humanos , Nigéria , Medição de Risco , Poluentes Químicos da Água/metabolismo
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