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1.
Acta Pharmaceutica Sinica ; (12): 266-273, 2021.
Article in Chinese | WPRIM | ID: wpr-872628

ABSTRACT

Xianling Gubao is a common and effective medicine in the treatment of orthopedic diseases. In recent years, it has been reported to be associated with liver injury. However, through the analysis of the adverse drug reaction reports and key hospital cases, we found that there is considerable incomplete information in the reports of Xianling Gubao-related liver injury cases retrieved from the literature. Thus, it is difficult to accurately judge causality between the drug and liver injury. Six cases of liver injury related to Xianling Gubao were identified in key hospitals, two of which achieved the clinical diagnosis according to the assessment of the integrated evidence chain method. We further analyzed the public health data of all residents in Yinzhou. The gross incidence rate of Xianling Gubao-related liver injury was 0.034%, which corresponds to a level of rare incidence. This revealed that Xianling Gubao-related liver injury has significant divergence in individuals and an idiosyncratic nature. The gross incidence of liver injury related to Xianling Gubao was lower than that of other medicines for the treatment of orthopedic diseases. Based on the idiosyncratic drug-induced liver injury model mediated by immune stress, it was found that Epimedii Folium and Psoraleae Fructus were the major components that lead to liver injury, and the liver injury caused by a full prescription was less serious than that encountered with only Epimedii Folium and Psoraleae Fructus. This suggests that the other 4 herbs (Dipsaci Radix, Anemarrhenae Rhizoma, Rehmanniae Radix,Salviae Miltiorrhizae Radix et Rhizoma) can prevent/alleviate the liver injury. Through disassembled prescription analysis, we found that the attenuation efficacy of Salviae Miltiorrhizae Radix et Rhizoma was the most significant. In conclusion, Xianling Gubao may cause idiosyncratic liver injury in a tiny minority of susceptible individuals, but the incidence risk is lower than that of other commonly used drugs for orthopedic disease. Xianling Gubao should be discreetly applied to patients with immune stress. The major components that induced liver injury in Xianling Gubao were Epimedii Folium and Psoraleae Fructus, and Salviae Miltiorrhizae Radix et Rhizoma appears to attenuate this toxicity. This study provides a reference for the rational clinical medication with Xianling Gubao.

2.
Article in English | WPRIM | ID: wpr-785830

ABSTRACT

BACKGROUND AND OBJECTIVES: The exosomes released by mesenchymal stromal cells (MSCs) in classical FBS-containing media have been demonstrated as an alternative, cell-free therapy in various diseases including inflammatory bowel disease (IBD). It has been found that the function of exosomes is affected by culture condition. We previously developed a serum-free, xeno-free and chemically defined medium, and umbilical cord-derived MSCs in this medium retained the immunosuppressive capability.METHODS: In this study, we evaluated the immunosuppressive function of exosomes from MSCs (MSC-Exo) in defined medium and their therapeutic effect on treating colitis.RESULTS AND CONCLUSIONS: In vitro studies indicated that MSC-Exo reduced the concentration of pro-inflammatory cytokines IFN-γ, TNF-α and IL-1β, and increased the secretion of anti-inflammatory cytokines TGF-β1 and IL-10, but no significant change of inhibitory effect on peripheral blood mononuclear cells proliferation was shown. In vivo experimental colitis showed that administration of MSC-Exo was able to significantly ameliorate the disease activity index score, weight loss, colon shortening, and the histological colitis score through up-regulation anti-inflammatory responses and down-regulation of inflammatory responses. Moreover, the use of MSC-Exo (200 μg) led to an improved therapeutic efficacy when compared with MSCs at a dose of 1×10⁶ cells. Our findings indicate that the exosomes from MSCs in defined medium possess a certain degree of immunosuppressive effect in vitro and exhibit a therapeutic capability in a mouse model of DSS-induced colitis through suppressing inflammation mechanism.


Subject(s)
Animals , Colitis , Colon , Cytokines , Down-Regulation , Exosomes , In Vitro Techniques , Inflammation , Inflammatory Bowel Diseases , Interleukin-10 , Mesenchymal Stem Cells , Mice , Up-Regulation , Weight Loss
3.
Article in Chinese | WPRIM | ID: wpr-773699

ABSTRACT

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.


Subject(s)
Animals , Anti-Inflammatory Agents , Pharmacology , Colitis, Ulcerative , Drug Therapy , Dextran Sulfate , Drugs, Chinese Herbal , Pharmacology , Glycyrrhiza , Chemistry , Mice , Plant Extracts , Pharmacology , Tripterygium , Chemistry
4.
Article in Chinese | WPRIM | ID: wpr-773696

ABSTRACT

The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.


Subject(s)
Animals , Cytokines , Blood , Dermatitis, Allergic Contact , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Glycyrrhiza , Chemistry , Plant Extracts , Pharmacology , Tripterygium , Chemistry
5.
Acta Pharmaceutica Sinica ; (12): 1077-1084, 2017.
Article in Chinese | WPRIM | ID: wpr-779697

ABSTRACT

In this study, rats were used to evaluate the effect of Radix glycyrrhiza on reducing liver toxicity of Tripterygium wilfordii. Metabonomics techniques were used to analyze the changes of small molecular metabolites and the metabolic pathways involved in the beneficial process. Different groups of rats were given for the extractions from Tripterygium wilfordii and Tripterygium wilfordii together with Radix glycyrrhiza. The general state, pathological changes of liver tissue, biochemical indexes of liver function and the changes of inflammatory factors in rats were observed. The results showed that the liver tissue injury of Tripterygium wilfordii group was significant, and the injury was reduced by Radix glycyrrhiza. Biochemical indexes and inflammatory factors also suggested that Tripterygium wilfordii together with Radix glycyrrhizaeffectively decreased the liver toxicity. HPLC-MS/MS-IT-TOF was used to characterize the difference of serum metabolism in rats. Multivariate statistical analysis was used to screen 15 potential biomarkers, such as fatty acid, glycerol ester, glycerol phosphate, phosphatidylethanolamine and phosphatidylcholine. It mainly involved in 7 metabolic pathways, such as glycerol phospholipid metabolism, linoleic acid metabolism, alpha linoleic acid metabolism, and glycosyl phosphatidylinositol terminal biosynthesis. The results showed that the Tripterygium wilfordii compatibility of Radix glycyrrhizaeffectively decreased the liver toxicity induced by Tripterygium wilfordii. Phospholipid metabolism may be the key metabolic pathway of Tripterygium wilfordii hepatotoxicity and the target of Radix glycyrrhiza. This study provides a reference for the control of liver toxicity of Tripterygium wilfordii.

6.
Acta Pharmaceutica Sinica ; (12): 1063-1068, 2017.
Article in Chinese | WPRIM | ID: wpr-779695

ABSTRACT

By using the drug metabolizing enzyme inhibitors, the effects of metabolic factors on potential liver injury induced by the main component, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(trans-SG), in Polygonum multiflorum was investigated. The main metabolic enzyme isoforms involved in trans-SG metabolism were also screened. The results showed that trans-SG at the dosage 31 mg·kg-1 did not cause liver injury; and the combination of trans-SG with the phase I metabolic enzyme inhibitor, 1-benzylimidazole (10 mg·kg-1), did not change the degree of liver injury(compared with LPS + trans-SG group, P > 0.05). However, the combination of trans-SG with phase II metabolic enzyme inhibitor, ketoconazole(35 mg·kg-1), significantly increased the degree of liver injury(compared with LPS + trans-SG group, P < 0.05). The phase I metabolites of trans-SG were not detected in human liver microsomes phase I metabolism system, while the phase II trans-SG metabolites were detected in recombinant human UGT isozymes phase II metabolism system. Six isoforms of uridine diphosphate glucuronate transferase(UGT)exhibited abilities to metabolize trans-SG and the order of metabolic ability was: UGT1A1 > UGT1A9 > UGT1A7 > UGT1A10 > UGT2B7 > UGT1A8. The results showed that trans-SG was mainly metabolized by UGT in phase II metabolism. The inhibition of drug metabolizing enzymes of phase II can increase the liver injury susceptibility of trans-SG, which provides a reference to the evaluation of susceptible factors and drug incompatibility research of Polygonum multiflorum.

7.
Article in Chinese | WPRIM | ID: wpr-335813

ABSTRACT

To screen potential biomarkers of curcumin related to treating depression rats by using metabolomics means, so as to explore the antidepressant action mechanism of curcumin. The healthy male SD rats were randomly divided into four groups. Chronic unpredictable mild stress (CUMS) stimulation was conducted for modeling for 2 weeks, and then curcumin (200 mg•kg⁻¹) or venlafaxine (40 mg•kg⁻¹) was given by gavage administration. The blank group and model group rats were given with the same volume of 1% CMCNa normal saline, once per day for two weeks. The rats serum for each group was collected and LC/MS-IT-TOF method was used to characterize the metabolic differences. Also multivariate statistical analysis was used to screen possible potential biomarkers and analyze the possible metabolic pathways. After administration of curcumin and venlafaxine respectively, the depression indexes of CUMS model rats were all improved significantly (P<0.05), but there were no significant differences between curcumin and venlafaxine groups. In PCA and PLS-DA analysis after curcumin or venlafaxine intervention on CUMS model group rats, the small molecule metabolites level reflects a normal trend, and particularly for the curcumin group. Through metabonomics technology, 11 biomarkers associated with curcumin antidepressant effect were screened, and at the same time seven metabolic pathways were involved. The results showed that curcumin had antidepressant effects, which was evident in both macro and micro levels, comparable with positive drug of venlafaxine. The antidepressant effect of curcumin may be associated with the glycerol phospholipid metabolism, linoleic acid metabolism, pentose and glucuronic acid ester and ether lipid metabolism, but still need further exploration in the future.

8.
Article in Chinese | WPRIM | ID: wpr-230984

ABSTRACT

To explore the effect of the licorice-processed Tripterygium wilfordii on reducing the liver toxicity. In animal experiments, the liver toxicity of T. wilfordii was evaluated both before and after processing, and the differences in liver tissue biopsy, serum biochemical indexes and inflammatory cell factor among blank group, T. wilfordii group and licorice-processed T. wilfordii group were observed. Liver tissue biopsy results showed that liver tissue injury was obvious in T. wilfordii group, and no obvious injury was found in licorice-processed T. wilfordii group. As compared with the blank group, the levels of AST, ALT and CRE were significantly increased (P<0.01), UREA was increased (P<0.05), and ALB level was significantly decreased (P<0.01) in the T. wilfordii group. As compared with T. wilfordii group, the levels of AST, ALT, CRE, and UREA were decreased (P<0.01), while ALB was increased (P<0.01) in the licorice-processed T. wilfordii group. The results of inflammatory factors in rats showed that the levels of IL-1β, IL-6, and TNF-α in T. wilfordii group were significantly higher than those in blank group (P<0.01); the levels of IL-1β, IL-6, and TNF-α in licorice-processed T. wilfordii group were significantly lower than those in T. wilfordii group (P<0.01). Overall, licorice processing of T. wilfordii can effectively reduce the liver toxicity and reduce the liver injury caused by T. wilfordii. The experiment can provide reference for the clinical rational use of the T. wilfordii, and provide data support for the studies on reducing the liver toxicity of T. wilfordii by licorice processing.

9.
Article in Chinese | WPRIM | ID: wpr-230978

ABSTRACT

Liquid chromatography-mass spectrometry method was used for determination of metabolic fingerprint spectrum in rat serum, and the method of multivariate statistical analysis was used to compare the metabolism spectrum difference and screen significantly related biomarkers. The dynamic change trend was investigated at the same time. The dynamic metabonomics changes of liver injury in rats caused by Polygonum multifulorum(PM) were investigated; significantly related biomarkers were found and their dynamic change trend was investigated to provide basis for internal mechanism and early clinical diagnosis. There was certain difference in serum metabolic profile of the rats at different time points. Six potential biomarkers were screened through comparative analysis, including oleamide, lysoPC(16∶0), leukotriene A4, trans-tetra-dec-2-enoic acid, dihydrocortisol and 7a-hydroxydehydroepiandrosterone. These markers presented the dynamic change trend in the process of PM causing liver damage. The biomarkers contents had a significant change after one week of drug administration, more sensitive than ALT and AST. It can reveal the dynamic mechanism of PM causing liver damage and hepatic self-healing performance to some extent, with important application value and significance for monitoring liver function and early detecting diagnosis for patients with PM.

10.
Article in Chinese | WPRIM | ID: wpr-258442

ABSTRACT

In this paper, the spectrum-effect correlation analysis method was used to explore the main effective components of Tripterygium wilfordii for liver toxicity, and provide reference for promoting the quality control of T. wilfordii. Chinese medicine T.wilfordii was taken as the study object, and LC-Q-TOF-MS was used to characterize the chemical components in T. wilfordii samples from different areas, and their main components were initially identified after referring to the literature. With the normal human hepatocytes (LO2 cell line)as the carrier, acetaminophen as positive medicine, and cell inhibition rate as testing index, the simple correlation analysis and multivariate linear correlation analysis methods were used to screen the main components of T. wilfordii for liver toxicity. As a result, 10 kinds of main components were identified, and the spectrum-effect correlation analysis showed that triptolide may be the toxic component, which was consistent with previous results of traditional literature. Meanwhile it was found that tripterine and demethylzeylasteral may greatly contribute to liver toxicity in multivariate linear correlation analysis. T. wilfordii samples of different varieties or different origins showed large difference in quality, and the T. wilfordii from southwest China showed lower liver toxicity, while those from Hunan and Anhui province showed higher liver toxicity. This study will provide data support for further rational use of T. wilfordii and research on its liver toxicity ingredients.

11.
Article in Chinese | WPRIM | ID: wpr-330182

ABSTRACT

To investigate the difference of liver injury in rats gavaged with crude and processed Polygoni Multiflori Radix. The 75% ethanol extract of crude and processed Polygoni Multiflori Radix (50 g · kg(-1) crude medicine weight/body weight) were continuous oral administered to rats for 6 weeks. Serum biochemical indicators were dynamically detected, the change of liver histopathology was assessed 6 weeks later. Principal component analysis (PCA) was adopted to screen sensitive indicator of the liver damage induced by polygoni multiflori radix. Biochemical tests showed that the crude Polygoni Multiflori Radix group had significant increase of serum ALT, AST, ALP, DBIL and TBIL (P < 0.01 or P < 0.05) and significant decreases of serum IBIL and TBA (P < 0.01 or P < 0.05), while the processed Polygoni Multiflori Radix group showed no obvious changes, compared to the untreated normal group. Histopathologic analysis revealed that crude Polygoni Multiflori Radix group exhibited significant inflammatory cells infiltration in portal area around the blood vessels, tissue destruction and local necrosis of liver cells. There were not obvious pathological changes in processed Polygoni Multiflori Radix group. The results demonstrated that the injury effect of processed Polygoni Multiflori Radix on liver injury of rats was significantly lower than that of unprocessed, and that processing can effectively reduce the hepatotoxicity of Polygoni Multiflori Radix. Traditional transaminase liver function indicators were not sensitive for crude Polygoni Multiflori Radix induced liver damage. The serum content of DBIL and TBIL can reflect the liver damage induced by crude Polygoni Multiflori Radix early and can be sensitive indicators for clinical monitoring the usage of it.


Subject(s)
Animals , Chemical and Drug Induced Liver Injury , Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Chemistry , Toxicity , Female , Liver , Wounds and Injuries , Male , Plant Roots , Chemistry , Toxicity , Polygonum , Chemistry , Toxicity , Rats
12.
Article in Chinese | WPRIM | ID: wpr-337936

ABSTRACT

Toxicity of different processed was evaluated Polygoni Multiflori Radix by determining the hepatotoxic potency for selecting processing technology. Process Polygoni Multiflori Radix using high pressure steamed, Black Bean high pressure steamed, atmospheric steamed for different time. Using normal human hepatocytes (L02) as evaluation model, hepatotoxic potency as index to evaluate hepatotoxic potency of different processed Polygoni Multiflori Radix. Analysis chemical composition of some processed products by UPLC-MS. Hepatotoxic bioassay method cloud evaluate the toxicity of different Polygoni Multiflori Radix samples. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix, high pressure steamed three hours attenuated was better. Different processing methods have different effects on chemical constituents of Polygoni Multiflori Radix. Comparing with crude sample, the contents of gallic acid, 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside, emodin-8-O-beta glucoside and emodin were decreased in processed products with 3 kinds of different methods. The change trend of 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside content was similar with hepatotoxic potency. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix. Processing methods and time attenuated obvious impact on toxicity. Recommended further research on the attehuated standard control of Polygoni Multiflori Radix concocted.


Subject(s)
Biological Assay , Cell Line , Chemistry, Pharmaceutical , Methods , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Toxicity , Fallopia multiflora , Chemistry , Toxicity , Hepatocytes , Humans , Plant Roots , Chemistry , Toxicity
13.
Acta Pharmaceutica Sinica ; (12): 973-979, 2015.
Article in Chinese | WPRIM | ID: wpr-257039

ABSTRACT

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.


Subject(s)
Alanine Transaminase , Blood , Animals , Aspartate Aminotransferases , Blood , Bile Acids and Salts , Metabolism , Bilirubin , Blood , Chemical and Drug Induced Liver Injury , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Fallopia multiflora , Chemistry , HMGB1 Protein , Metabolism , Hepatocytes , Interleukin-1beta , Metabolism , Liver , Pathology , Plant Extracts , Pharmacology , Rats , Tumor Necrosis Factor-alpha , Metabolism
14.
Article in Chinese | WPRIM | ID: wpr-237720

ABSTRACT

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.


Subject(s)
Animals , Celastraceae , Chemistry , Metabolism , Toxicity , Chromatography, Liquid , Methods , Drugs, Chinese Herbal , Metabolism , Toxicity , Liver , Metabolism , Male , Mass Spectrometry , Methods , Rats , Rats, Sprague-Dawley
15.
Acta Pharmaceutica Sinica ; (12): 28-33, 2015.
Article in Chinese | WPRIM | ID: wpr-251822

ABSTRACT

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.


Subject(s)
Alanine Transaminase , Blood , Animals , Aspartate Aminotransferases , Blood , Chemical and Drug Induced Liver Injury , Pathology , Hepatocytes , Pathology , Lipopolysaccharides , Polygonum , Toxicity , Rats , Rats, Sprague-Dawley
16.
Article in Chinese | WPRIM | ID: wpr-268746

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of transforming growth factor beta (TGF ) on c-fos gene expression in hepatic stellate cells.</p><p><b>METHODS</b>Hepatic stellate cells (HSC-T6) were cultured in the medium containing different concentrations of TGF (0.2, 1, and 5 ng/ml), and cells were collected at different time points of incubation (8, 24, 48, and 72 h). The total RNA of the HSCs was isolated and c-fos gene expression level were measured by reverse transcription polymerase chain reaction.</p><p><b>RESULTS</b>c-fos gene expression levels of HSCs cultured in the presence of low (0.2 ng/ml), moderate (1 ng/ml) and high (5 ng/ml) concentrations of TGF for 8, 24, 48 and 72 h were significantly greater than those of control group. The c-fos gene expression levels of HSCs increased gradually with the increment of TGF concentration, and significant differences in c-fos gene expression were found between the 3TGF groups.</p><p><b>CONCLUSION</b>TGF strongly up-regulates c-fos gene expression in hepatic stellate cells.</p>


Subject(s)
Animals , Cells, Cultured , Gene Expression , Genes, fos , Hepatic Stellate Cells , Proto-Oncogene Proteins c-fos , Genetics , Metabolism , Rats , Transforming Growth Factor beta , Pharmacology
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