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1.
Biosci Biotechnol Biochem ; 84(1): 171-177, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31476130

RESUMO

We tested the hypothesis that α-lactalbumin inhibits the disruption of intestinal barrier function and liver cirrhosis by restoring gut-liver axis function in thioacetamide (TAA) -treated rats. Rat diets were supplemented with α-lactalbumin replacing 50% of dietary protein. After consuming α-lactalbumin for one week, rats were intraperitoneally injected with TAA twice a week for 14 weeks. The α-lactalbumin-enriched diet significantly inhibited the elevation of plasma alanine aminotransferase, aspartate aminotransferase, and hyaluronic acids. The supplement significantly reduced plasma lipopolysaccharide levels and increased occludin mRNA level. Hepatic fibrosis and regenerative nodules was developed and intestinal villi were shortened by TAA; α-Lactalbumin attenuated these histopathological changes. These results indicated that α-lactalbumin improved intestinal barrier function, suppressing endotoxin levels. These data also suggested that α-lactalbumin ameliorated the impairment of the gut-liver axis by TAA, inhibiting the development of liver cirrhosis.


Assuntos
Suplementos Nutricionais , Trato Gastrointestinal/efeitos dos fármacos , Lactalbumina/uso terapêutico , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/dietoterapia , Fígado/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tioacetamida/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Fibrose/tratamento farmacológico , Trato Gastrointestinal/metabolismo , Expressão Gênica/efeitos dos fármacos , Ácido Hialurônico/sangue , Injeções Intraperitoneais , Lipopolissacarídeos/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/prevenção & controle , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Tioacetamida/administração & dosagem , Proteínas de Junções Íntimas/genética
2.
Chemosphere ; 239: 124747, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31514003

RESUMO

BACKGROUNDS: Polychlorinated biphenyls are persistent environmental pollutants associated with the onset of non-alcoholic fatty liver disease in humans, but there is limited information on the underlying mechanism. In the present study, we investigated the alterations in gene expression profiles in normal human liver cells L-02 following exposure to 2, 3, 3', 4, 4', 5 - hexachlorobiphenyl (PCB 156), a potent compound that may induce non-alcoholic fatty liver disease. METHODS: The L-02 cells were exposed to PCB 156 for 72 h and the contents of intracellular triacylglyceride and total cholesterol were subsequently measured. Microarray analysis of mRNAs and long non-coding RNAs (lncRNAs) in the cells was also performed after 3.4 µM PCB 156 treatment. RESULTS: Exposure to PCB 156 (3.4 µM, 72 h) resulted in significant increases of triacylglyceride and total cholesterol concentrations in L-02 cells. Microarray analysis identified 222 differentially expressed mRNAs and 628 differentially expressed lncRNAs. Gene Ontology and pathway analyses associated the differentially expressed mRNAs with metabolic and inflammatory processes. Moreover, lncRNA-mRNA co-expression network revealed 36 network pairs comprising 10 differentially expressed mRNAs and 34 dysregulated lncRNAs. The results of bioinformatics analysis further indicated that dysregulated lncRNA NONHSAT174696, lncRNA NONHSAT179219, and lncRNA NONHSAT161887, as the regulators of EDAR, CYP1B1, and ALDH3A1 respectively, played an important role in the PCB 156-induced lipid metabolism disorder. CONCLUSION: Our findings provide an overview of differentially expressed mRNAs and lncRNAs in L-02 cells exposed to PCB 156, and contribute to the field of polychlorinated biphenyl-induced non-alcoholic fatty liver disease.


Assuntos
Fígado/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Transcriptoma/efeitos dos fármacos , Aldeído Desidrogenase/genética , Linhagem Celular , Colesterol/metabolismo , Citocromo P-450 CYP1B1/genética , Receptor Edar/genética , Perfilação da Expressão Gênica , Humanos , Fígado/citologia , Fígado/fisiologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante , RNA Mensageiro/metabolismo , Testes de Toxicidade , Triglicerídeos/metabolismo
3.
Adv Exp Med Biol ; 1182: 217-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777021

RESUMO

Ganoderma lucidum (G. lucidum, Lingzhi) has a wide range of hepatoprotective effects. Its bioactive substances include triterpenoids, polysaccharides, sterols, steroids, peptides, and other bioactive ingredients. Based on our research and other references, this chapter discusses the hepatoprotective effects of G. lucidum in different liver diseases, including hepatocellular carcinoma, nonalcoholic liver disease, alcoholic liver disease, hepatitis B, inflammation, fibrosis, and toxicant-induced liver injury. The liver protective mechanisms of G. lucidum vary from diseases to diseases. This chapter will summarize the hepatoprotective effects of G. lucidum on different liver injury and their clinical applications.


Assuntos
Produtos Biológicos/farmacologia , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Reishi/química , Humanos
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 684-687, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762238

RESUMO

OBJECTIVE: To explore the protective effects of quercetin (QE) on triptolide (TP) induced liver injury and the relevant mechanism. METHODS: Forty C57BL/6 mice were equally divided into 4 groups, control group, TP model group, 20 mg/kg QE treatment group and 80 mg/kg QE treatment group randomly. The 20 mg/kg and 80 mg/kg QE groups were gastrointestinal administration with QE at the dose of 0.2 mL/10 g for 10 d, twice daily, while other groups were administrated with equivalent normal saline. Four hours post the last dose, animals were gastrointestinal administered with TP at a dose of 500 µg/kg per mouse, except for NS control. All the mice were sacrificed 22 h later, blood and liver tissue samples were collected. The pathologic change of liver tissue was detected by HE staining. The level of aminotransferase (AST) and aspartate alanine aminotransferase (ALT) in serum, and the level of glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue homogenates were detected using the commercial kits. The level of interleukin (IL)-17, IL-10 and IL-6 in liver tissue homogenates was measured by ELISA. Hepatic expression of Toll-like receptor 4 (TLR4) was detected by Western blot. RESULTS: Compared with the control group, in the TP model group, hepatic lobule structure atrophied and even disappeared, hepatic cell necrosis and inflammatory cell infiltration are obvious. Additionally, in TP model group, serum ALT, AST and MDA levels were significantly increased, SOD and GSH levels were decreased, IL-6 and IL-17 levels were increased, IL-10 levels were decreased, and TLR4 protein levels were increased (P < 0.05). Compared with the TP model group, liver tissue injury and inflammatory cell infiltration were reduced in the QE group, and serum levels of ALT, AST, MDA, IL-6 and IL-17 were all decreased. TLR4 expression was down-regulated (P < 0.05) in both QE groups, and the decease levle was more significant in the high-dose QE group (P < 0.05, compared with the low-dose QE group). CONCLUSION: Quercetin can reduce TP-induced liver injury by reducing oxidative damage, promoting antioxidant and regulating cytokine secretion.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Quercetina/farmacologia , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Diterpenos , Compostos de Epóxi , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Fenantrenos , Distribuição Aleatória
5.
Biochemistry (Mosc) ; 84(9): 1093-1106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31693469

RESUMO

Differential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome profiling on a microchip. Relative mRNA expression levels of the Asah2, Crot, Crtc2, Fmo3, GSTA2, LOC1009122026, LOC102551184, NpY, NqO1, Prom1, Retsat, RGD1305464, Tmem104, and Whsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs). Significant changes in the expression of steroid metabolism gene were observed in the liver of animals fed with the tested diets (except the high-fat high fructose diet). Both high-fat and high-fructose diets caused a significant decrease in the expression of squalene synthase (FDFT1 gene) responsible for the initial stage of cholesterol synthesis. On the contrary, in animals fed with the high-cholesterol diet (0.5% cholesterol), expression of the FDFT1 gene did not differ from the control group; however, these animals were characterized by changes in the expression of glucose and glycogen synthesis genes, which could lead to the suppression of glycogen synthesis and gluconeogenesis. At the same time, this group demonstrated different liver tissue morphology in comparison with the animals fed with the high-fructose high-fat diet, manifested as the presence of lipid vacuoles of a smaller size in hepatocytes. The high-fructose and high-fructose high-fat diets affected the metabolic pathways associated with intracellular protein catabolism (endocytosis, phagocytosis, proteasomal degradation, protein processing in the endoplasmic reticulum), tight junctions and intercellular contacts, adhesion molecules, and intracellular RNA transport. Rats fed with the high-fructose high-fat or high-cholesterol diets demonstrated consistent changes in the expression of the Crot, Prom1, and RGD1305464 genes, which reflected a coordinated shift in the regulation of lipid and carbohydrate metabolisms.


Assuntos
Colesterol/farmacologia , Gorduras na Dieta/farmacologia , Açúcares da Dieta/farmacologia , Frutose/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , RNA/genética , Transcriptoma/efeitos dos fármacos , Animais , Colesterol/administração & dosagem , Colesterol/metabolismo , Biologia Computacional , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Açúcares da Dieta/administração & dosagem , Açúcares da Dieta/metabolismo , Feminino , Frutose/administração & dosagem , Frutose/metabolismo , Perfilação da Expressão Gênica , Fígado/citologia , RNA/análise , RNA/isolamento & purificação , Ratos , Ratos Wistar , Transcriptoma/genética
6.
Biochemistry (Mosc) ; 84(10): 1197-1203, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694515

RESUMO

Here, we suggested that the epigenetic mechanism of benzo(a)pyrene (BP) action might be based on the aryl hydrocarbon receptor (AhR)-mediated transcription of the target genes, including miRNAs, that have the dioxin response element (DRE) in their promoters. The effect of BP on the expression of the oncogenic miR-483-3p, its host gene IGF2, and target gene IGF1 in primary hepatocytes and in the liver of Wistar female rats was investigated. The activation of AhR was confirmed using selective AhR inhibitor CH-223191 and by evaluating expression of the target CYP1A1 gene. The lack of coordination between the expression of miR-483-3p and its host gene IGF2 was revealed, which may be due to the presence of the binding site for the estrogen receptor alpha (ERα), which is a negative expression regulator. Our results confirm the existence of the AhR-mediated pathway in the regulation of expression of miR-483-3p, IGF1, and IGF2 under BP exposure, which is of considerable interest for understanding the epigenetic mechanisms of the carcinogenic effect of BP.


Assuntos
Benzo(a)pireno/farmacologia , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Animais , Células Cultivadas , Biologia Computacional , Feminino , Hepatócitos/metabolismo , Fígado/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Ratos Wistar
7.
J Photochem Photobiol B ; 201: 111643, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31698218

RESUMO

Diabetes is a major emerging health consequence across the world which directly associated with the obesity. Contemporary anti-diabetic drugs have numeral limitations, and investigation of herbal remedies for diabetes give novel guide for the expansion of new drugs that can be used as harmonizing to present anti-diabetic allopathic medications. Gold nanoparticles (AuNPs) of 21 nm have been formerly well portrayed in vitro for their capability to intend active uptake in cell. Our present study was dealing with the synthesis of gold nanoparticles by means of Smilax glabra rhizome amend the anti-obesity constraints in high-fat diet by streptozotocin provoked obese diabetes in rat model. Characterization studies like UV -Spectroscopy, XRD analysis, SEM, TEM microscopy, Energy Dispersive X-Ray Spectroscopy, and FT-IR investigation confirms the availability of dimension, shape and size. Biochemical parameters like blood glucose and insulin sufferance and its release, lipid profile, aterogenic & coronary index, liver markers, inflammatory markers, hormones like leptin, resistin, adiponectin indicates the therapeutic effect of gold nanoparticles harvested from Smilax glabra on obese and diabetic rats. Histopathological examinations displayed the disturbed internal structures of obese and diabetic rats liver and heart tissues. Whereas, treatment with gold nanoparticles synthesized from Smilax glabra restored the internal membrane, nuclei and cytoplasm. All these findings confirmed the anti-obesity and anti-diabetic effect of synthesized gold nanoparticles from Smilax glabra.


Assuntos
Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Ouro/química , Nanopartículas Metálicas/química , Smilax/química , Animais , Glicemia/análise , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/química , Ratos , Ratos Wistar , Rizoma/química , Rizoma/metabolismo , Smilax/metabolismo , Estreptozocina/toxicidade
8.
Biomed Khim ; 65(5): 388-397, 2019 Aug.
Artigo em Russo | MEDLINE | ID: mdl-31666411

RESUMO

Fibrates are well-known agonists of the PPAR family (peroxisome proliferator-activated receptors). This class of drugs is used for the treatment of dyslipidemia and atherosclerosis. Fenofibrate is one of the members of this class of synthetic PPARα receptor ligands. The oral administration of 0.3% fenofibrate caused a decrease in strength due to loss of body weight in laboratory animals when improving behavioural features. Analysis of the mitochondrial DNA of liver cells showed a genotoxic effect of fenofibrate, due to accumulation of reactive oxygen species, which could be attributed to activation of peroxisomal ß-oxidation processes, as well as to the lack of increase in the expression of genes encoding antioxidant defense proteins. Treatment with fenofibrate did not cause brain mtDNA damage. It has been shown that fenofibrate induced mitochondrial ß-oxidation in the brain, as indicated by the increased expression of the Acadm and Cpt1a and Ppargc1a and Ppara. The study found no effect of fenofibrate on the increase of mitochondrial biogenesis in brain and liver cells. Thus, we can conclude that fenofibrate significantly affects lipid metabolism in the liver and brain, but in the liver it is associated with an increase of oxidative stress, resulting in mtDNA oxidative damage. However, fenofibrate-induced increase in the expression of Ppargc1a is not associated with an increase of mitochondrial biogenesis. This is consistent with the recent suggestion that PGC-1α might not be a master regulator of mitochondrial biogenesis.


Assuntos
Encéfalo/efeitos dos fármacos , Dano ao DNA , Ácidos Graxos/metabolismo , Fenofibrato/farmacologia , Fígado/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Regulação da Expressão Gênica , Fígado/metabolismo , Camundongos
9.
Bratisl Lek Listy ; 120(11): 843-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31747765

RESUMO

INTRODUCTION: The aim of this study is to investigate the effects of obstructive jaundice on the liver and effectivity of alpha­lipoic acid on liver damage and oxidative stress. MATERIALS AND METHODS: Thirty­six male Sprague­Dawley rats were divided into 3 groups per 12 animals, namely into Group I (control group): the bile duct was only mobilized by laparotomy, Group II (bile duct ligation group - BDL): the common bile duct was closed with clips and OJ was caused after laparotomy, and Group III (bile duct ligation and alpha­lipoic acid group - BDL+LA): after closing the common bile duct, LA was administered in an intramuscular dose of 50 mg/kg for 10 days. On the 10th day, malondialdehyde, glutathione and superoxide dismutase levels were measured in liver and histopathological evaluation was performed. RESULTS: AST (U/L)/ALT(U/L) in groups I, II and III were 155.33/51.83, 445.28/165.89, 380.78/173.33, respectively (p < 0.005). Superoxide dismutase and glutathione levels were lower in patient groups than in the control group (0.31 µl/g vs 0.36 µl/g; p < 0.05). After the lipoic acid treatment, none of the biochemical markers of liver improved. Only the increase in superoxide dismutase (0.31 µl/g and 0.34 µl/g in groups II and III, respectively) and glutathione levels (0.16 µl/g and 0.22 µl/g in groups II and III, respectively) was statistically significant (p < 0.05). CONCLUSIONS: Histopathological damage was statistically significantly decreased and antioxidant levels were statistically significantly increased after LA treatment (Tab. 1, Fig. 6, Ref. 23).


Assuntos
Icterícia Obstrutiva/tratamento farmacológico , Estresse Oxidativo , Ácido Tióctico/farmacologia , Animais , Antioxidantes/análise , Ductos Biliares , Glutationa/análise , Humanos , Ligadura , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/análise , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Superóxido Dismutase/análise
10.
An Acad Bras Cienc ; 91(4): e20180975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721920

RESUMO

This study investigated the ability of formulation containing Zingiber officinale (ginger) to reverse health changes promoted by unhealthy diet in Wistar rats. Five compounds from the gingerol family and three from the shogaol family were identified in the chromatographic analyzes of the extract. The animals were fed a combination of unhealthy foods, the cafeteria diet, which promoted increases in body weight, hepatocyte nucleus area, total hepatocyte area and liver fat accumulation, as well as reduced hepatic glutathione S-transferase concentration, compared to the control group, which received commercial chow. The treatment with ginger improved all these results, highlighting the reduction of 10% of body weight and 66% of the total area of lipid droplets deposited, compared to the group that received the cafeteria diet. Ginger treatments also attenuated lipid peroxidation, with a mean reduction of 41% in malondialdehyde levels and a mean increase of 222% in glutathione S-transferase activity in the liver. The cafeteria diet and ginger extract did not promote significant changes in glycemic and lipid profile, liver weight and liver enzymes compared to the control group. We suggest that ginger can have beneficial effects on health complications associated with unhealthy diet, such as excessive adiposity, oxidative stress and hepatic injury.


Assuntos
Antioxidantes/farmacologia , Gengibre/química , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ganho de Peso/etnologia , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/lesões , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
11.
Acta Cir Bras ; 34(8): e201900805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618405

RESUMO

PURPOSE: To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury. METHODS: Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. RESULTS: The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. CONCLUSION: The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Isquemia/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , Peroxidase/análise , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
12.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2947-2952, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602838

RESUMO

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1ß) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1ß and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citocinas/metabolismo , Eleutherococcus/química , Polissacarídeos/farmacologia , Animais , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Peptídeos Cíclicos , Distribuição Aleatória , Transdução de Sinais
13.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2953-2959, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602839

RESUMO

This study aimed to investigate the protective effect and preliminary mechanism of Danzhi Jiangtang Capsules( DJC) on liver of hyperlipidemic rats. The hyperlipidemia models were successfully made by high-fat diet for 12 weeks in male SD rats,and then divided into model control group and DJC treatment groups( 500 and 1 000 mg·kg~(-1)·d-1) via gavage administration for additional 8 weeks.The levels of serum lipid and liver metabolism indices were detected; HE and oil red O staining were used to observe the pathological changes of liver. Expression levels of extracellular regulated protein kinase 1/2( ERK1/2),c-Jun N-terminal kinase( JNK),and p38 mitogen-activated protein kinase( p38 MAPK) were detected by real-time polymerase chain reaction( RT-PCR). Expression of MCP-1,phosphorylated ERK( p-ERK),phosphorylated JNK( p-JNK),and phosphorylated p38 MAPK( p-p38) were analyzed by immunohistochemistry and Western blot. The results showed that DJC decreased body weight and serum levels of total cholesterol( TC),triglyceride( TG),alanine aminotransferase( ALT),aspartate aminotransferase( AST),increased serum high-density lipoprotein cholesterol( HDL-C) level,ameliorate injury and lipid deposition in the liver induced by the high-fat diet,decreased mRNA expression of ERK1/2,JNK and p-38 MAPK as well as protein expression of p-ERK,p-JNK,p-p38,and MCP-1,somewhat showing a dose-dependent effect. Therefore,DJC has an obvious protective effect on liver of hyperlipidemic rats with certain dose-dependent effect,and the mechanism may be related with inhibiting MAPK pathways and inflammation.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/tratamento farmacológico , Sistema de Sinalização das MAP Quinases , Animais , Cápsulas , Dieta Hiperlipídica , Inflamação , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2960-2965, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602840

RESUMO

The study aimed to investigate the mechanism of hepatoprotective effect of C-21 steroidal glucosides from Cynanchum auriculatum( Baishouwu) on oxidative stress in mice with liver injury. Mice were randomly divided into normal group,model group,positive control group,Baishouwu high group and Baishouwu low group. The liver injury model was induced by intraperitoneal injection of CCl4 peanut oil solution. All mice were sacrificed to collect blood and liver specimens. The activities of serum levels of ALT and AST were detected. The content of MDA and the activity of SOD in liver homogenate were examined by colorimetry method. Tissues were stained with hematoxylin-eosin for histological examination. The hepatic protein expressions of NF-κB p65,p-IκBα,i NOS and COX-2 were detected by Western blot. The mRNA expressions of TNF-α and IL-6 were determined by RT-PCR. It was found that treatment with C-21 steroidal glucosides from Baishouwu successfully attenuated liver injury induced by CCl4,as shown by decreased levels of serum biochemical indicators( AST,ALT)( P<0. 01). Administration of total C-21 steroidal glucosides enhanced the activity of SOD( P<0. 01) and decreased the content of MDA( P<0. 01) in liver homogenate. Microscopic features suggested that treatment with C-21 steroidal glucosides from Baishouwu was effective in inhibiting CCl4-induced hepatocyte edema and degeneration. Further studies showed that NF-κB p65 overexpression induced by CCl4 was decreased by C-21 steroidal glucosides,leading to the markedly down-regulated protein expression levels of p-IκBα,i NOS and COX-2,as well as the depression of TNF-α and IL-6 mRNA expressions. In conclusion,total C-21 steroidal glucosides from Baishouwu exhibited potent effect on oxidative stress pathway in mice with liver injury induced by CCl4,with enhanced activity of SOD,decreased content of MDA,and down-regulated levels of NF-κB p65,p-IκBα,i NOS and COX-2.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cynanchum/química , Glucosídeos/farmacologia , Estresse Oxidativo , Animais , Tetracloreto de Carbono , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos , Distribuição Aleatória
15.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2966-2971, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602841

RESUMO

To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1ß( IL-1ß) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1ß,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Metabolismo Energético , Inflamação/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , Citocinas/metabolismo , Galactosamina , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Distribuição Aleatória , Sirtuínas/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3468-3477, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602911

RESUMO

Tripterygium wilfordii multiglycoside( GTW),an extract derived from T. wilfordii,has been used for rheumatoid arthritis and other immune diseases in China. However its potential hepatotoxicity has not been investigated completely. Firstly,the content of triptolid( TP) in GTW was 0. 008% confirmed by a LC method. Then after oral administration of GTW( 100,150 mg·kg-1) and TP( 12 µg·kg-1) in female Wistar rats for 24 h,it was found that 150 mg·kg-1 GTW showed more serious acute liver injury than 12 µg·kg-1 TP,with the significantly increased lever of serum ALT,AST,TBA,TBi L,TG and bile duct hyperplasia even hepatocyte apoptosis. The expression of mRNA and proteins of liver bile acid transporters such as BSEP,MRP2,NTCP and OATP were down-regulated significantly by GTW to inhibit bile acid excretion and absorption,resulting in cholestatic liver injury. Moreover,GTW was considered to be involved in hepatic oxidative stress injury,although it down-regulated SOD1 and GPX-1 mRNA expression without significant difference in MDA and GSH levels. In vitro,we found that TP was the main toxic component in GTW,which could inhibit cell viability up to 80% in Hep G2 and LO2 cells at the dose of 0. 1 µmol·L-1. Next a LC-MS/MS method was used to detect the concentration of triptolid in plasma from rats,interestingly,we found that the content of TP in GTW was always higher than in the same amount of TP,suggesting the other components in GTW may affect the TP metabolism. Finally,we screened the substrate of p-glycoprotein( p-gp) in Caco-2 cells treated with components except TP extrated from GTW,finding that wilforgine,wilforine and wilfordine was the substrate of p-gp. Thus,we speculated that wilforgine,wilforine and wilfordine may competitively inhibit the excretion of TP to bile through p-gp,leading to the enhanced hepatotoxity caused by GTW than the same amount of TP.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Diterpenos/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/toxicidade , Fenantrenos/toxicidade , Tripterygium/toxicidade , Animais , Células CACO-2 , Cromatografia Líquida , Compostos de Epóxi/toxicidade , Feminino , Humanos , Fígado/efeitos dos fármacos , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem
17.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3494-3501, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602914

RESUMO

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , Apoptose , Feminino , Heme Oxigenase-1/metabolismo , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Distribuição Aleatória , Comprimidos , Proteína X Associada a bcl-2/metabolismo
18.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3526-3532, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602918

RESUMO

This paper aims to investigate the effect of oral administration of Tripterygium Glycosides Tablets combined with traditional Chinese medicine on immune inflammatory index in patients with rheumatoid arthritis,in order to explore the compatibility mode of traditional Chinese medicine in the treatment of rheumatoid arthritis. Medical records of hospitalized patients with rheumatology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2012 to December 2017 were collected. The combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine was adopted for the experimental group,while the simply administration of Tripterygium Glycosides Tablets were adopted for the control group. SPSS 21. 0 was used to analyze the changes of general conditions and immune inflammatory metabolic indexes in the two groups of RA patients. The association rules were analyzed by SPSS Clementine 14. 2 software Apriori module,and the random walk model was evaluated by ORACLE 10 g tool. The results showed that a total of 1 220 patients with rheumatoid arthritis met the requirements of this study,including 322 in the experimental group and 898 in the control group. Before treatment,there was no significant difference in age and duration between the two groups. The difference value of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR in the two groups of RA patients decreased before and after treatment,and the experimental group was superior to the control group in reduction of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR.The control group was superior to the experimental group in reduction of Ig M( P<0. 01 or P<0. 05). Compared with before treatment,ALT,AST,ALP,GGT,CREA,BUN,b-MG,MA,TRU and Ig U all increased,with statistically significant differences( P<0. 01).The UA of the two groups of RA patients decreased after treatment,with statistically significant differences( P<0. 01). The experimental group was superior to the control group in reduction of UA,with statistically significant differences( P < 0. 05 or P < 0. 01). The herbs adopted in the prescriptions of 1 220 patients were mainly classified into four categories,namely spleen-sweating herbs,blood-activating and stasis-relieving herbs,phlegm and phlegm-relieving herbs,and heat-clearing and antidote herbs. The results of association rule analysis indicated a significant correlation between the single-flavored Tripterygium Glycosides Tablets,oral Chinese medicine and immune inflammation,and improvement of liver and kidney function indexes. The results of the random walk model analysis indicated that the experimental group's Ig M and hs-CRP were superior to those of the control group in terms of random fluctuation maximum,walking positive growth rate,comprehensive evaluation index increasing rate,comprehensive improvement rate,comprehensive evaluation index recording times,and expected improvement value. The results of this study showed that the single administration of Tripterygium Glycosides Tablets can effectively improve the immune inflammatory metabolic index of patients with rheumatoid arthritis,and the combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine could alleviate the immune inflammatory index of RA patients and reduce liver and kidney dysfunction compared with simple oral administration. The comprehensive evaluation Ig M and hs-CRP in the group of combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine were better than those in the group of the Tripterygium Glycosides Tablets. There was a long-term correlation between the comprehensive evaluation index and the intervention measures of the two groups of patients.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Mineração de Dados , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Tripterygium/química , Humanos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Medicina Tradicional Chinesa , Comprimidos
19.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 628-633, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594081

RESUMO

Objective: To investigate the change in expression of anti-senescence marker protein calmodulin (RGN) in liver tissues of rats with immune hepatic fibrosis, and to observe the effect of compound glutathione inosine injection (CGII) on it. Methods: Rat liver fibrosis model was induced by intraperitoneal injection of porcine serum, and CGII intervention was administered at the appropriate time. Rat liver tissues were stained with HE and Masson. RGN and protein expression at mRNA in liver tissues was detected by fluorescence quantitative PCR and immunohistochemistry. One-way Anova was used for measurement data. LDS test was used for two-way comparison, and pathological semi-quantitative results were analyzed by rank-sum test. Results: The relative expression of RGN mRNA and protein in liver tissue of fibrotic rats was 82.23 ± 15.21 and 12.52 ± 3.23, respectively, which were significantly lower than that of normal rats 176.39 ± 11.35 and 59.23 ± 9.13 (P < 0.01). The degree of liver fibrosis in fibrotic rats after CGII intervention was significantly lower than fibrotic rats. The relative expression of RGN mRNA and protein in the intervention group was 168.78 ± 21.31 and 46.42 ± 4.71, respectively, which were significantly higher than fibrosis and spontaneous recovery group. The difference was statistically significant (P < 0.01). The relative expression of RGN mRNA and protein in the spontaneous recovery group was 86.23 ± 17.16 and 14.34 ± 5.16, which was higher than model group. The difference was not statistically significant (P > 0.05). Conclusion: The expression of RGN in liver tissue of rats with hepatic fibrosis induced by porcine serum is decreased, while the expression of RGN increases with the decrease of fibrosis after CGII intervention, suggesting that the protein may play an important role in the development of liver fibrosis.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Glutationa/farmacologia , Inosina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Cirrose Hepática Experimental/tratamento farmacológico , Animais , Hidrolases de Éster Carboxílico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática Experimental/metabolismo , Ratos , Ratos Sprague-Dawley , Suínos
20.
Anticancer Res ; 39(10): 5495-5504, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570443

RESUMO

BACKGROUND/AIM: Most patients with hepatocellular carcinoma (HCC) cannot be treated using traditional therapies. Boron neutron capture therapy (BNCT) may provide a new treatment for HCC. In this study, the therapeutic efficacy and radiobiological effects of boric acid (BA)-mediated BNCT in a VX2 multifocal liver tumor-bearing rabbit model are investigated. MATERIALS AND METHODS: Rabbits were irradiated with neutrons at the Tsing Hua Open Pool Reactor 35 min following an intravenous injection of BA (50 mg 10B/kg BW). The tumor size following BNCT treatment was determined by ultrasonography. The radiobiological effects were identified by histopathological examination. RESULTS: A total of 92.85% of the tumors became undetectable in the rabbits after two fractions of BNCT treatment. The tumor cells were selectively eliminated and the tumor vasculature was collapsed and destroyed after two fractions of BA-mediated BNCT, and no injury to the hepatocytes or blood vessels was observed in the adjacent normal liver regions. CONCLUSION: Liver tumors can be cured by BA-mediated BNCT in the rabbit model of a VX2 multifocal liver tumor. BA-mediated BNCT may be a breakthrough therapy for hepatocellular carcinoma.


Assuntos
Ácidos Bóricos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/efeitos da radiação , Terapia por Captura de Nêutron de Boro/métodos , Hepatócitos/efeitos dos fármacos , Hepatócitos/efeitos da radiação , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Masculino , Coelhos
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