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1.
Mol Nutr Food Res ; : e2000003, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32438504

RESUMO

SCOPE: [6]-gingerol is one of the primary pungent constituents of ginger. While [6]-gingerol has many pharmacological effects, its benefits for myocardial fibrosis, including its exact role and underlying mechanisms, remain largely unexplored. The present study was designed to characterize the cardio-protective effects of [6]-gingerol in myocardial fibrosis mice and possible underlying mechanisms. SCOPE: [6]-gingerol is one of the primary pungent constituents of ginger. While [6]-gingerol has many pharmacological effects, its benefits for myocardial fibrosis, including its exact role and underlying mechanisms, remain largely unexplored. The present study was designed to characterize the cardio-protective effects of [6]-gingerol in myocardial fibrosis mice and possible underlying mechanisms METHODS AND RESULTS: Mice were subcutaneously injected with isoproterenol (ISO, 10mg/kg) and gavaged with [6]-gingerol (10, 20 mg/kg/day) for 14 days. Pathological alterations, fibrosis, oxidative stress, inflammation response, and apoptosis were examined. In ISO-induced myocardial fibrosis, [6]-gingerol treatment decreased the J-point, heart rate, cardiac weight index (CWI), left ventricle weight index (LVWI), creatine kinase (CK) and lactate dehydrogenase (LDH) serum levels, calcium concentration, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione disulfide (GSSG), increased levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and GSH/GSSG. Further, [6]-gingerol improved ISO-induced morphological pathologies, reduced the expression of TNF-α, IL-6, c-fos, c-jun, Bax, Caspase-3, TLR4, NF-κB, p38, p-p38, ERK1/2, p-ERK1/2, JNK, and p-JNK, and increased Bcl-2 protein expression. CONCLUSION: The protective effect of [6]-gingerol in mice with ISO-induced myocardial fibrosis may be related to the inhibition of oxidative stress, inflammation, and apoptosis, potentially through the TLR4/MAPKs/NF-κB signaling pathway. This article is protected by copyright. All rights reserved.

2.
Sci Rep ; 8(1): 5423, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29615664

RESUMO

Polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. 4-bromodiphenyl ether (BDE-3), the photodegradation products of higher brominated PBDEs, is the most fundamental mono-BDE in environment but is less studied. The purpose of this study was to investigate the reproductive toxicity induced by BDE-3 and explore the mechanism by metabolomics approach. In this study, mice were treated intragastrically with BDE-3 for consecutive six weeks at the dosages of 0.0015, 1.5, 10 and 30 mg/kg. The reproductive toxicity was evaluated by sperm analysis and histopathology examinations. UPLC-Q-TOF/MS was applied to profile the metabolites of testis tissue, urine and serum samples in the control and BDE-3 treated mice. Results showed the sperm count was dose-dependently decreased and percentage of abnormal sperms increased by the treatment of BDE-3. Histopathology examination also revealed changes in seminiferous tubules and epididymides in BDE-3 treated mice. Metabolomics analysis revealed that different BDE-3 groups showed metabolic disturbances to varying degrees. We identified 76, 38 and 31 differential metabolites in testis tissue, urine and serum respectively. Pathway analysis revealed several pathways including Tyrosine metabolism, Purine metabolism and Riboflavin metabolism, which may give a possible explanation for the toxic mechanism of BDE-3. This study indicates that UHPLC-Q-TOFMS-based metabolomics approach provided a better understanding of PBDEs-induced toxicity dynamically.


Assuntos
Éteres Difenil Halogenados/toxicidade , Metabolômica , Reprodução/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Contagem de Espermatozoides , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/fisiologia
3.
Toxicol Mech Methods ; 27(9): 687-696, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28701067

RESUMO

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fígado/efeitos dos fármacos , Espectrometria de Massas/métodos , Metabolômica , Extratos Vegetais/toxicidade , Veratrum/química , Animais , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
Biomed Chromatogr ; 31(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28544073

RESUMO

The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analyzing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry and hydrophilic interaction liquid chromatography mass spectrometry that are based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram and echocardiograph monitoring of cardiac function and pathological examination were performed on mice in both the control and VN groups, and it was verified that acute heart injury was caused. Meanwhile, comparing the results of the control and VN groups, we detected 36 differential endogenous metabolites of heart tissue, including taurine, riboflavin, purine and lipids, which are related to many possible pathways such as purine metabolism, taurine and hypotaurine metabolism and energy metabolism. Our study provides a scientific approach for evaluating and revealing the mechanisms of VN-induced cardiotoxicity via the metabolomic strategy.


Assuntos
Cardiotoxinas/toxicidade , Cromatografia Líquida de Alta Pressão/métodos , Metaboloma/efeitos dos fármacos , Extratos Vegetais/toxicidade , Veratrum/química , Animais , Cardiotoxicidade/metabolismo , Cardiotoxinas/química , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Espectrometria de Massas/métodos , Redes e Vias Metabólicas , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/química
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