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1.
BMC Plant Biol ; 21(1): 436, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563114

RESUMO

BACKGROUND: Nitrogen, as a limiting factor for net primary productivity in grassland ecosystems, is an important link in material cycles in grassland ecosystems. However, the nitrogen assimilation efficiency and mechanisms of grassland plants under grazing disturbance are still unclear. This study investigated Stipa breviflora desert steppe which had been grazed for 17 years and sampled the root system and leaf of the constructive species Stipa breviflora during the peak growing season under no grazing, light grazing, moderate grazing and heavy grazing treatments. The activities of enzymes related to nitrogen assimilation in roots and leaves were measured. RESULTS: Compared with no grazing, light grazing and moderate grazing significantly increased the activities of nitrate reductase (NR), glutamine synthetase (GS), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) in leaves, and GS, GOT and GPT in roots of Stipa breviflora, while heavy grazing significantly decreased the activities of GS in leaves and NR in roots of Stipa breviflora. NR, GOT and GPT activities in leaves and roots of Stipa breviflora were positively correlated with nitrogen content, soluble protein, free amino acid and nitrate content. CONCLUSIONS: Grazing disturbance changed the activities of nitrogen assimilation related enzymes of grassland plants, and emphasized that light grazing and moderate grazing were beneficial for nitrogen assimilation by grassland plants. Therefore, establishing appropriate stocking rates is of great significance for material flows in this grassland ecosystem and for the stability and sustainable utilization of grassland resources.


Assuntos
Ativação Enzimática/fisiologia , Pradaria , Herbivoria , Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Poaceae/metabolismo , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , China , Glutamato-Amônia Ligase/metabolismo , Nitrato Redutase/metabolismo
2.
Bratisl Lek Listy ; 122(10): 732-738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570575

RESUMO

BACKGROUND: The use of acetaminophen (APAP) is increasing recently, especially with COVID-19 outbreaks. APAP is safe at therapeutic levels, however, an overdose can cause severe liver injury. This study aims to explore possible mechanisms involved in APAP­induced hepatotoxicity and compare different hepatoprotective agents, namely vitamin E, hydrogen sulfide (H2S) and necrostatin-1 (NEC-1). METHODS: Adult male albino rats were divided into groups: Control group, APAP­induced hepatotoxicity group, Vitamin E­treated group, H2S­treated group and NEC-1­treated group. Serum levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF-α), reduced glutathione (GSH) and lipid profile were measured. Histopathological examinations of liver tissue with H(et)E stain and immunohistochemistry for activated caspase-3 were also done. RESULTS: APAP­treated group showed elevated liver transaminases, hyperlipidemia, and deficient liver anti-oxidative response together with disturbed hepatic architecture and increased immune-expression of activated caspase-3 in hepatic tissue. Pretreatment with vitamin E, H2S or NEC-1 reversed the affected parameters. Vitamin E and H2S showed greater improvement when compared to NEC-1. CONCLUSION: Vitamin E, H2S and NEC-1 showed protective effects against APAP-induced hepatotoxicity, thus they may be used as an adjuvant therapy when APAP is indicated for long periods as is the case in COVID-19 patients (Tab. 2, Fig. 2, Ref. 45). Text in PDF www.elis.sk Keywords: acetaminophen, hepatotoxicity, apoptosis, necrostatin-1, vitamin E, H2S.


Assuntos
COVID-19 , Doença Hepática Induzida por Substâncias e Drogas , Sulfeto de Hidrogênio , Acetaminofen/toxicidade , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Humanos , Sulfeto de Hidrogênio/metabolismo , Imidazóis , Indóis , Fígado/metabolismo , Masculino , Estresse Oxidativo , Ratos , SARS-CoV-2 , Vitamina E/farmacologia
3.
Life Sci ; 284: 119881, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389403

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin α5ß1, and human ACE2 to facilitate viral entry into host cells in vitro. We previously found that inhibition of integrin α5ß1 by the clinically validated small peptide ATN-161 inhibits these spike protein interactions and cell infection in vitro. In continuation with our previous findings, here we have further evaluated the therapeutic potential of ATN-161 on SARS-CoV-2 infection in k18-hACE2 transgenic (SARS-CoV-2 susceptible) mice in vivo. We discovered that treatment with single or repeated intravenous doses of ATN-161 (1 mg/kg) within 48 h after intranasal inoculation with SARS-CoV-2 lead to a reduction of lung viral load, viral immunofluorescence, and improved lung histology in a majority of mice 72 h post-infection. Furthermore, ATN-161 reduced SARS-CoV-2-induced increased expression of lung integrin α5 and αv (an α5-related integrin that has also been implicated in SARS-CoV-2 interactions) as well as the C-X-C motif chemokine ligand 10 (Cxcl10), further supporting the potential involvement of these integrins, and the anti-inflammatory potential of ATN-161, respectively, in SARS-CoV-2 infection. To the best of our knowledge, this is the first study demonstrating the potential therapeutic efficacy of targeting integrin α5ß1 in SARS-CoV-2 infection in vivo and supports the development of ATN-161 as a novel SARS-CoV-2 therapy.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Oligopeptídeos/uso terapêutico , SARS-CoV-2/fisiologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , COVID-19/virologia , Genoma Viral , Humanos , Integrinas/metabolismo , Fígado/enzimologia , Fígado/patologia , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oligopeptídeos/farmacologia , SARS-CoV-2/genética , Coloração e Rotulagem , Carga Viral/genética
4.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200394

RESUMO

Zinc is an effective anti-inflammatory and antioxidant trace element. The aim of this study was to analyse the protective effect of zinc and zinc-prolactin systems as additives of preservation solutions in the prevention of nephron damage caused during ischemia. The study used a model for storing isolated porcine kidneys in Biolasol®. The solution was modified with the addition of Zn at a dose of 1 µg/L and Zn: 1 µg/L with prolactin (PRL): 0.1 µg/L. After 2 h and 48 h of storage, the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatinine and total protein were determined. Zinc added to the Biolasol® composition at a dose of 1 µg/L showed minor effectiveness in the protection of nephrons. In turn, Zn2+ added to Biolasol + PRL (PRL: 0.1 µg/L) acted as a prolactin inhibitor. We do not recommend the addition of Zn(II) (1 µg/L) and Zn(II) (1 µg/L) + PRL (0.1 µg/L) to the Biolasol solution.


Assuntos
Isquemia/metabolismo , Rim/metabolismo , Prolactina/metabolismo , Zinco/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Creatinina/metabolismo , Criopreservação/métodos , L-Lactato Desidrogenase/metabolismo , Preservação de Órgãos/métodos , Perfusão/métodos , Potássio/metabolismo , Sódio/metabolismo , Suínos
5.
Arch Insect Biochem Physiol ; 108(2): e21836, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34288123

RESUMO

In Asian rice systems, Cyrtorhinus lividipennis Reuter is an important predator that preys on rice planthopper eggs and young nymphs, as a primary food source. Alanine aminotransferase (ALT) acts in many physiological and biochemical processes in insects. We cloned the full-length complementary DNA of C. lividipennis ClALT. Expression analysis showed higher expression in the fat body and midgut compared to other tissues. It is expressed in all C. lividipennis developmental stages and at least four organs. Silencing of ClALT by RNA interference significantly decreased the ClALT enzyme activity and ClALT expression compared to dsGFP-treated controls at 2 days after emergence (DAE). Silencing of ClALT influenced free hemolymph amino acid compositions, resulting in a reduction of Aspartic acid (Asp) and Alanine (Ala) proportions, and increased Cysteine (Cys) and Valine (Val) proportions in females at 2 DAE. dsClALT treatments led to decreased soluble total protein concentrations in ovary and fat body, and to lower reduced vitellogenin (Vg) expression, body weight, and the numbers of laid eggs. The double-stranded RNA viruse treatments also led to prolonged preoviposition periods and hindered ovarian development. Western blot analysis indicated that silencing ClALT also led to reduced fat body Vg protein abundance at 2 DAE. These data support our hypothesis that ClALT influences amino acid metabolism and fecundity in C. lividipennis.


Assuntos
Alanina Transaminase , Aminoácidos/metabolismo , Fertilidade , Heterópteros , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Aminoácidos/genética , Animais , Hemolinfa/metabolismo , Heterópteros/genética , Heterópteros/metabolismo , Heterópteros/fisiologia , Proteínas de Insetos/metabolismo , Interferência de RNA , Vitelogeninas/metabolismo
6.
Exp Cell Res ; 406(1): 112719, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34273405

RESUMO

Hepatic ischemia/reperfusion injury (IRI) is an adverse effect for liver transplantation which is characterized by immune response mediated inflammation. Recent studies report that neutrophil extracellular traps (NETs) are implicated in hepatic IRI. The aim of this study was to explore the mechanism of action of tetramethylpyrazine (TMP), the main chemical composition of Ligusticum chuanxiong in treatment of ischemic related diseases. Data showed that hepatic IRI increases the leak of alanine aminotransferase (ALT) and aspartate transaminase (AST), and stimulates formation of NETs. Extracellular DNA/NETs assay, hematoxylin-eosin (HE) staining, immunofluorescence assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot assay, showed that TMP significantly reduces formation of NETs and alleviates hepatic IRI. Moreover, TMP and Diphenyleneiodonium (DPI) suppressed ROS production in neutrophils. In addition, analysis showed that activation of NADPH oxidase plays a role in formation of NETs triggered by hepatic IRI. Notably, TMP inhibited formation of NETs though inhibition of NADPH oxidase. Additionally, Combination treatment using TMP and DPI was more effective compared with monotherapy of either of the two drugs. These findings show that combination therapy using TMP and DPI is a promising method for treatment hepatic IRI.


Assuntos
Antioxidantes/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Transplante de Fígado/reabilitação , Oniocompostos/farmacologia , Pirazinas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Ácidos Nucleicos Livres/antagonistas & inibidores , Ácidos Nucleicos Livres/sangue , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Armadilhas Extracelulares/metabolismo , Marcação In Situ das Extremidades Cortadas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/cirurgia , Transplante de Fígado/métodos , Masculino , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/cirurgia , Resultado do Tratamento
7.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069402

RESUMO

The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.


Assuntos
Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Polietilenoglicóis/farmacologia , Alanina Transaminase/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Criopreservação/métodos , Fígado Gorduroso/metabolismo , Glutationa/metabolismo , Fígado/citologia , Masculino , Microcirculação/efeitos dos fármacos , Mitocôndrias/metabolismo , Óxido Nítrico/metabolismo , Soluções para Preservação de Órgãos/farmacologia , Ratos , Ratos Zucker , Manejo de Espécimes/métodos
8.
Phytomedicine ; 87: 153588, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091148

RESUMO

BACKGROUND: Cholestasis is characterized by accumulation of bile components in liver and systemic circulation. Restoration of bile acid homeostasis via activating farnesoid x receptor (FXR) is a promising strategy for the treatment of cholestasis. FXR-SHP (small heterodimer partner) axis plays an important role in maintaining bile acid homeostasis. PURPOSE: To investigate the anti-cholestasis effect of Dolomiaea souliei (Franch.) C.Shih (D. souliei) and clarify its underlying mechanism against α-naphthylisothiocyanate (ANIT) induced acute intrahepatic cholestasis. METHODS: ANIT-induced Sprague-Dawley rats were employed to investigate the anti-cholestasis effect of D. souliei ethyl acetate extract (DSE). Ursodeoxycholic acid (UDCA) was used as positive control. Bile flow and blood biochemical parameters were measured. Liver histopathological examination was conducted via hematoxylin-eosin staining. Western blot analysis was carried out to evaluate the protein levels related to bile acids metabolism and inflammation. The interactions between FXR and costunolide or dehydrocostus lactone, were conducted by molecular docking experiments. The effect of costunolide and dehydrocostus lactone on aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and FXR expression were also evaluated using guggulsterone-induced L02 cells. RESULTS: DSE could promote bile excretions and protect against ANIT-induced liver damage in cholestasis rats. Protein levels of FXR, SHP, Na+/taurocholate cotransporter (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) were increased and the expressions of cholesterol 7α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) were decreased by DSE. Meanwhile, the anti-inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) were also significantly increased, and the pro-inflammatory factor, interleukin-10 (IL-10), was significantly decreased in rats of DSE groups. Molecular docking revealed that costunolide and dehydrocostus lactone could be well docked into the FXR protein molecule, and hydrophobic interactions played the main function. Costunolide could reverse the increased AST and ALT levels and increase the FXR expression in guggulsterone-induced L02 cells. CONCLUSION: DSE had an anti-cholestasis effect by activating FXR-SHP axis, inhibiting synthesis of bile acid, and increasing bile secretion, together with inflammatory response and improving liver injury. Costunolide may be the main active component. This study provided a potential therapeutic mechanism for D. souliei as an anti-cholestasis medicine in the treatment of cholestasis liver diseases.


Assuntos
Asteraceae/química , Ácidos e Sais Biliares/metabolismo , Colestase Intra-Hepática/tratamento farmacológico , Extratos Vegetais/farmacologia , 1-Naftilisotiocianato/toxicidade , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Acetatos/química , Alanina Transaminase/metabolismo , Animais , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Lactonas/química , Masculino , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Sesquiterpenos/química
9.
Ecotoxicol Environ Saf ; 220: 112398, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34116333

RESUMO

Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg·BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.


Assuntos
Anti-Infecciosos/toxicidade , Colistina/toxicidade , Enrofloxacina/toxicidade , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Quinoxalinas/toxicidade , Drogas Veterinárias/toxicidade , Alanina Transaminase/metabolismo , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Aspartato Aminotransferases/metabolismo , Colistina/administração & dosagem , Combinação de Medicamentos , Resíduos de Drogas , Enrofloxacina/administração & dosagem , Exposição Ambiental , Perfilação da Expressão Gênica , Humanos , Fígado/enzimologia , Fígado/patologia , Masculino , Quinoxalinas/administração & dosagem , Ratos Sprague-Dawley , Fatores de Tempo , Drogas Veterinárias/administração & dosagem
10.
Medicine (Baltimore) ; 100(22): e25817, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087824

RESUMO

INTRODUCTION: The efficacy of soy diet for nonalcoholic fatty liver disease remains controversial. We conduct a systematic review and meta-analysis to explore the influence of soy diet vs placebo on the treatment of non-alcoholic fatty liver disease. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through October 2020 for randomized controlled trials assessing the efficacy of soy diet vs placebo for nonalcoholic fatty liver disease. This meta-analysis is performed using the random-effect model. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group for nonalcoholic fatty liver disease, soy diet is associated with significantly reduced HOMA-IR (standard mean difference [SMD] = -0.42; 95% confidence interval [CI] = -0.76 to -0.08; P = .01), increased insulin (SMD = -0.64; 95% CI = -0.98 to -0.30; P = .0002) and decreased malondialdehyde (SMD = -0.43; 95% CI = -0.74 to -0.13; P = .005), but demonstrated no substantial impact on body mass index (SMD = 0.17; 95% CI = -0.20 to 0.53; P = .37), alanine aminotransferase (SMD = -0.01; 95% CI = -0.61 to 0.60; P = .98), aspartate-aminotransferase (SMD = 0.01; 95% CI = -0.47 to 0.49; P = .97), total cholesterol (SMD = 0.05; 95% CI = -0.25 to 0.35; P = .73) or low density lipoprotein (SMD = 0; 95% CI = -0.30 to 0.30; P = .99). CONCLUSIONS: Soy diet may benefit to alleviate insulin resistance for nonalcoholic fatty liver disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica/dietoterapia , Proteínas de Soja/uso terapêutico , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Humanos , Insulina/metabolismo , Lipídeos/sangue , Malondialdeído/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas de Soja/administração & dosagem
11.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073834

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid ß-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos/metabolismo , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores Purinérgicos P2Y2/metabolismo , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Peso Corporal , Antígenos CD36/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Insulina/sangue , Resistência à Insulina/fisiologia , Lipase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Obesidade/metabolismo , Receptores Purinérgicos P2Y2/deficiência , Receptores Purinérgicos P2Y2/genética , Estearoil-CoA Dessaturase/metabolismo
12.
Mol Cell Biochem ; 476(9): 3433-3448, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33973131

RESUMO

Amiodarone (AMD) is a widely used antiarrhythmic drug prescribed to treat cardiac tachyarrhythmias; however, AMD has been reported to provoke pulmonary fibrosis (PF) and hepatotoxicity. This study aimed to investigate the influence of alpha lipoic acid (ALA) on AMD-induced PF and hepatotoxicity in male Wistar rats. AMD administration resulted in elevated lung contents of hydroxyproline (Hyp), malondialdehyde (MDA), and increased serum levels of transforming growth factor beta-1 (TGF-ß1), interferon-γ (IFN-γ), alanine amino transaminase (ALT), aspartate amino transaminase (AST), total cholesterol (TC), and glucose. On the other side, lung content of glutathione reduced (GSH) and serum levels of total anti-oxidant capacity (TAC) were significantly decreased. Histopathologically, AMD caused PF, produced a mild hepatic injury, and increased expression of alpha smooth muscle actin (α-SMA). Treatment with ALA produced a significant reversal of the oxidative stress, fibrosis, and inflammation parameters with reductions in α-SMA expressions, leading to amelioration of histopathological lesions. ALA might provide supportive therapy in AMD-receiving cardiovascular patients.


Assuntos
Amiodarona/toxicidade , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Substâncias Protetoras/farmacologia , Fibrose Pulmonar/prevenção & controle , Ácido Tióctico/farmacologia , Alanina Transaminase/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos , Ratos Wistar , Vasodilatadores/toxicidade
13.
Fish Physiol Biochem ; 47(4): 1119-1132, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34057672

RESUMO

This study was conducted to assess the impacts of prolonged fasting (70 and 120 days) on the morphological, biochemical, oxidative stress responses, immune-related gene expression, histopathology, and DNA damage in rainbow trout. Final weight (FW), hepatosomatic index (HSI), and condition factor (CF) significantly decreased in both 70 and 120 days of fasting compared to the pre-fasting group (p < 0.05). Fasting led to a significant reduction in serum blood metabolites (glucose, total protein, triglyceride, T. cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)) and endogenous reserves (protein and lipid). However, plasma acetylcholinesterase (AChE) activity, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin (IL1), tumor necrosis factor (TNF1α), and transferrin (TF) increased significantly (p < 0.05). While malondialdehyde (MDA) levels compared to the pre-fasting group increased in the liver and muscle tissues (70 and 120 days), glutathione (GSH) enzyme activities decreased significantly in both tissues (p < 0.05). Histopathologically, both fasting groups (70 and 120 days) when compared to the pre-fasting group led to steatosis, necrosis and degeneration in hepatocytes, inflammation and hyperemia in the liver tissue and hyaline degeneration, atrophy, and inflammation in muscle tissue. Additionally, 8-OHdG levels of the liver and muscle tissues at 120 days' fasting were more severe according to 70 days' fasting. Finally, blood, the liver, and muscle tissues may be helpful to assess the impacts of fasting and fasting stress in rainbow trout.


Assuntos
Jejum/metabolismo , Oncorhynchus mykiss , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Acetilcolinesterase/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Dano ao DNA , Proteínas de Peixes/genética , Expressão Gênica , Glutationa/metabolismo , Interleucina-1/genética , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Músculos/metabolismo , Músculos/patologia , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/crescimento & desenvolvimento , Oncorhynchus mykiss/imunologia , Oncorhynchus mykiss/metabolismo , Estresse Oxidativo , Transferrina/genética , Fator de Necrose Tumoral alfa/genética
14.
Food Chem Toxicol ; 153: 112263, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34015426

RESUMO

In this study, the changes in oncogenic and tumor suppressor signaling pathways in liver and their association with serum and urinary biomarkers of aflatoxin exposure were evaluated in Wistar rats fed diets containing aflatoxin B1 (AFB1) for 90 days. Rats were divided into four groups (n = 15 per group) and assigned to dietary treatments containing 0 (control), 50 (AFB50), 100 (AFB100) and 200 µg AFB1 kg-1 diet (AFB200). Multiple preneoplastic foci of hepatocytes marked with glutathione-S-transferase-placental form (GST-P) were identified in AFB100 and AFB200 groups. Hepatocellular damage induced by AFB1 resulted in overexpression of cyclin D1 and ß-catenin. The liver expression of retinoblastoma (Rb) and p27Kip1 decreased in AFB100 and AFB200 groups, confirming the favorable conditions for neoplastic progression to hepatocellular carcinoma. All samples from rats fed AFB1-contaminated diets had quantifiable AFB1-lysine in serum or urinary AFM1 and AFB1-N7-guanine, with mean levels of 20.42-50.34 ng mL-1, 5.31-37.68 and 39.15-126.37 ng mg-1 creatinine, respectively. Positive correlations were found between AFB1-lysine, AFM1 or AFB1-N7-guanine and GST-P+, ß-catenin+ and cyclin D1+ hepatocytes, while Rb + cells negatively correlated with those AFB1 exposure biomarkers. The pathways evaluated are critical molecular mechanisms of AFB1-induced hepatocarcinogenesis in rats.


Assuntos
Aflatoxina B1/toxicidade , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteína do Retinoblastoma/metabolismo , beta Catenina/metabolismo , Aflatoxina B1/análogos & derivados , Aflatoxina B1/sangue , Aflatoxina B1/metabolismo , Aflatoxina B1/urina , Aflatoxina M1/urina , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Expressão Gênica/efeitos dos fármacos , Guanina/análogos & derivados , Guanina/urina , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Lisina/sangue , Masculino , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos Wistar
15.
Med Sci Monit ; 27: e930688, 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934098

RESUMO

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.


Assuntos
Encefalopatias/diagnóstico , Influenza Humana/diagnóstico , Doença Aguda , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aquaporinas/sangue , Aquaporinas/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Encefalopatias/sangue , Encefalopatias/metabolismo , Líquido Cefalorraquidiano/metabolismo , Pré-Escolar , Feminino , Glucocorticoides/sangue , Glucocorticoides/metabolismo , Humanos , Imunoglobulinas Intravenosas/sangue , Imunoglobulinas Intravenosas/metabolismo , Influenza Humana/sangue , Influenza Humana/metabolismo , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Neuroimagem/métodos , Convulsões/sangue , Convulsões/diagnóstico , Convulsões/metabolismo
16.
PLoS One ; 16(4): e0230833, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886563

RESUMO

Ischaemic Hepatitis (IH) or Hypoxic Hepatitis (HH) also known as centrilobular liver cell necrosis is an acute liver injury characterized by a rapid increase in serum aminotransferase. The liver injury typically results from different underlying medical conditions such as cardiac failure, respiratory failure and septic shock in which the liver becomes damaged due to deprivation of either blood or oxygen. IH is a potentially lethal condition that is often preventable if diagnosed timely. The role of mechanisms that cause IH is often not well understood, making it difficult to diagnose or accurately quantify the patterns of related biomarkers. In most patients, currently, the only way to determine a case of IH is to rule out all other possible conditions for liver injuries. A better understanding of the liver's response to IH is necessary to aid in its diagnosis, measurement, and improve outcomes. The goal of this study is to identify mechanisms that can alter associated biomarkers for reducing the density of damaged hepatocytes, and thus reduce the chances of IH. We develop a mathematical model capturing dynamics of hepatocytes in the liver through the rise and fall of associated liver enzymes aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) related to the condition of IH. The model analysis provides a novel approach to predict the level of biomarkers given variations in the systemic oxygen in the body. Using IH patient data in the US, novel model parameters are described and then estimated for the first time to capture real-time dynamics of hepatocytes in the presence and absence of IH condition. The results may allow physicians to estimate the extent of liver damage in an IH patient based on their enzyme levels and receive faster treatment on a real-time basis.


Assuntos
Hepatócitos/patologia , Isquemia/metabolismo , Hepatopatias/metabolismo , Fígado/enzimologia , Oxigênio/metabolismo , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Hepatite/metabolismo , Hepatite/patologia , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Humanos , Hipóxia/metabolismo , Hipóxia/patologia , Isquemia/patologia , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias/patologia , Modelos Biológicos
17.
Arch Virol ; 166(7): 1853-1858, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33871695

RESUMO

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log10 IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log10 IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-ß1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-ß1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-ß3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-ß3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-ß 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-ß2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-ß level might be an independent factor related to the occurrence of CHB.


Assuntos
Hepatite B Crônica/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adulto , Alanina Transaminase/metabolismo , Citocinas/metabolismo , DNA Viral/genética , Feminino , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Masculino , Estudos Prospectivos
18.
Med Sci Monit ; 27: e929438, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33850093

RESUMO

BACKGROUND Hepatic stellate cells (HSCs) play a vital role in hepatic fibrogenesis. Our recent clinical study indicated that the Zi Qi decoction, a Traditional Chinese Medicine formula, exhibited good efficacy in alleviating liver fibrosis, but the underlying mechanism remains elusive. MATERIAL AND METHODS Rats repeatedly injected with CCl4 and cells stimulated with lipopolysaccharide were used as in vivo and in vitro models for liver fibrosis, respectively. The viability of LX-2 cells was evaluated with MTT assay. Relative messenger RNA (mRNA) expression of representative extracellular matrix (ECM) components was detected with real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, total and phosphorylation levels of ECM proteins and pathway-related proteins were detected with western blotting. Immunofluorescent staining was used to show the nuclear translocation of nuclear factor kappa b (NF-kappaB) p65. Hematoxylin & eosin (H&E) and Masson trichrome staining and immunohistochemistry were performed to evaluate the extent of liver fibrosis. The levels of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), Hyp, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were tested with an enzyme-linked immunosorbent assay. In addition, 7.0T micro-magnetic resonance imaging (micro-MRI) was used to evaluate the severity of hepatic damage. RESULTS The Zi Qi decoction inhibited lipopolysaccharide-mediated upregulation of mRNA and protein levels of representative ECM proteins both in vivo and in vitro. The Zi Qi decoction also suppressed activation of the Toll-like receptor 4 (TLR4)-related NF-kappaB signaling pathway and subsequently inhibited the nuclear translocation of activated NF-kappaB. Moreover, another TLR4 downstream pathway, mitogen-activated protein kinase (MAPK), was simultaneously restrained. The results of liver pathology and MRI in rat models also suggested the efficacy of the Zi Qi decoction in attenuating liver damage. CONCLUSIONS The Zi Qi decoction inhibited liver fibrosis by inhibiting the TLR4-related NF-kB and MAPK signaling pathways and preventing activation of HSCs.


Assuntos
Misturas Complexas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Células Estreladas do Fígado/fisiologia , Cirrose Hepática/terapia , Fígado/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Medicina Tradicional Chinesa , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo
19.
PLoS One ; 16(4): e0249346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861750

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.


Assuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Síndrome do Desconforto Respiratório/virologia , Adulto , Idoso , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/virologia , Creatinina/sangue , Creatinina/metabolismo , Egito/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Contagem de Linfócitos , Linfopenia/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/epidemiologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
20.
Molecules ; 26(7)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800652

RESUMO

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.


Assuntos
Antídotos/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Clorpirifos/toxicidade , Inseticidas/toxicidade , Litsea/química , Acetilcolinesterase/metabolismo , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antídotos/isolamento & purificação , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/metabolismo , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Bilirrubina/metabolismo , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Clorpirifos/antagonistas & inibidores , Creatinina/metabolismo , Inseticidas/antagonistas & inibidores , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Fitoterapia/métodos , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/química
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