1.Evaluation on hepatotoxicity caused by Dioscorea bulbifera based on analysis of bile acids.
Ying XU ; Chong-Chong CHEN ; Li YANG ; Jun-Ming WANG ; Li-Li JI ; Zheng-Tao WANG ; Zhi-Bi HU
Acta Pharmaceutica Sinica 2011;46(1):39-44
Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.
Animals
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Bile Acids and Salts
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metabolism
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Chemical and Drug Induced Liver Injury
;
metabolism
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Cholic Acid
;
metabolism
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Chromatography, High Pressure Liquid
;
methods
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Dioscorea
;
toxicity
;
Drugs, Chinese Herbal
;
isolation & purification
;
toxicity
;
Heterocyclic Compounds, 4 or More Rings
;
isolation & purification
;
toxicity
;
Least-Squares Analysis
;
Male
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Mice
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Mice, Inbred ICR
;
Plants, Medicinal
;
toxicity
;
Principal Component Analysis
;
Rhizome
;
toxicity
;
Tandem Mass Spectrometry
;
methods
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Taurochenodeoxycholic Acid
;
metabolism
;
Taurocholic Acid
;
metabolism
;
Taurodeoxycholic Acid
;
metabolism
2.Study on preparing taurine and some taurat salts
Pharmaceutical Journal 2004;34(11):15-19
Study was performed on the preparation of taurine and some taurate salts in the bile of cow/ox from vissan but chery firm. Average weight of bile adder get 80 g for each. From ethamlanin and die thylcarbonate, 2- oxzolidinon was prepared, after the heating with hydrogene sulphide, taurine was obtained with a productivity of 67,15%. The investigation and extraction of taurine in laboratory scale gave a productivity of 64,5%. From taurine, calcium taurate was prepared at a productivity of 90% and magnesium taurate- 83,5%
Taurine
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Salts
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Pharmaceutical Preparations
3.Effect of Tauroursodeoxycholic acid on cytochrome C-mediated apoptosis in HepG2 cells.
Qing XIE ; Guang-ming LI ; Xia-qiu ZHOU ; Dan LIAO ; Hong YU ; Qing GUO
Chinese Journal of Hepatology 2003;11(5):298-301
OBJECTIVETo investigate the effect of Tauroursodeoxycholic acid (TUDCA) on Taurodeoxycholic acid (TDCA)-induced HepG2 cell apoptosis and to clarify the molecular mechanism of its anti-apoptosis effect of TUDCA.
METHODSMorphologic evaluation of apoptotic cells was performed by Hoechst 33258 staining and electron microscope. DNA fragment was detected by electrophoresis on 1.5% agarose gels. Apoptosis rate was measured by flow cytometry using PI dye. Following incubation of HepG2 cells either with TDCA alone, or coincubation with TUDCA and TDCA, the releasing level of cytochrome c from mitochondria into cytosol was determined by western blot, also the activity of caspase-3, 8, 9.
RESULTSIncubating the cells with 400 micromol/L TDCA for 12 h induced the cells apoptosis significantly. The apoptotic rate decreased from 50.35% +/- 2.20% to 13.78% +/- 0.84% after coincubation with TUDCA, and this anti-apoptotic effect of TUDCA was confirmed by morphological and DNA ladder detection. TUDCA significantly inhibited the release of cytochrome C from mitochondria into cytosol, and the activity of caspase-9, 3 (t > or = 13.00, P < 0.01), especially at 12 h, caspase-3 activity decreased by 54.9% (t = 16.88, P < 0.01) and 52.5%, however it had no obvious effect on the activity of caspase-8 (t = 1.94, P > 0.05).
CONCLUSIONSTUDCA prevents HepG2 cells apoptosis induced by TDCA through modulating mitochondrial membrane stability, inhibiting the release of cytochrome c and the activation of procaspase-9 and 3. Anti-apoptotic mechanism of TUDCA may be considered to be one of the most important reasons that TUDCA exerts significant efficacy in the treatment of cholestatic liver diseases.
Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Caspase 3 ; Caspase 9 ; Caspases ; metabolism ; Cytochromes c ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Taurochenodeoxycholic Acid ; pharmacology ; Taurodeoxycholic Acid ; analogs & derivatives ; pharmacology ; Tumor Cells, Cultured
4.Effects of taurine on cadmium exposure in muscle, gill, and bone tissues of Carassius auratus.
Kyung Soon CHOI ; Il Su YOO ; Kyung Ok SHIN ; Keun Hee CHUNG
Nutrition Research and Practice 2013;7(1):22-25
This study was performed in order to investigate the effects of taurine on cadmium poisoning in muscle, gill, and bone tissues of wild goldfish. For this experiment, 80 wild goldfish were divided into four experimental groups: 0.3 mg/L of cadmium and 0 mg/L of taurine (Group I), 0.3 mg/L of cadmium and 20 mg/kg of taurine (Group II), 0.3 mg/L of cadmium and 40 mg/L of taurine (Group III), and 0.3 mg/L of cadmium and 80 mg/L of taurine (Group IV). The results were as follows: The cadmium concentration in muscle tissue of wild goldfish was 0.65-3.21 mg/kg wet wt in Group I, whereas it decreased in Group IV. Levels of cadmium in gill tissue of wild goldfish were 16.57-42.39 mg/kg wet wt in Group I, 15.23-43.01 mg/kg wet wt in Group II, 15.11-39.56 mg/kg wet wt in Group III, and 13.15-38.55 mg/kg wet wt in Group IV (P < 0.05), suggesting that the cadmium concentration decreased in the experimental groups compared to control. The cadmium concentration in bone tissue of wild goldfish after 28 days was 0.52-9.75 mg/kg in Group II, whereas it increased in Group III (P < 0.05). In conclusion, taurine may have a preventive effect against cadmium accumulation in biological tissues.
Animals
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Bone and Bones
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Cadmium
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Cadmium Poisoning
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Gills
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Goldfish
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Muscles
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Taurine
5.Immediate Anticoagulation for Acute Cardioembolic Stroke is Still Popular in Selective Cases in Korea.
Ju Hun LEE ; Kwang Yeol PARK ; Ji Hoe HEO ; Sun U KWON
Korean Journal of Stroke 2011;13(3):120-128
BACKGROUND: Although current guidelines do not recommend immediate anticoagulation therapy (IAC) for acute ischemic stroke, judicious debates are still lingering on whether it might be done for acute cardioembolic stroke (ACES). We surveyed current practice patterns of anticoagulation therapy for ACES in Korea, and analyzed their related factors. METHODS: Using a web-based system, all neurology staffs of training hospitals in Korea surveyed about when and how they commenced anticoagulation therapy in the hypothetical cases with ACES. RESULTS: Of the 359 subjects invited, 281 responded to the e-mail, of whom 76 abstained from participating. The number of participants was therefore 205 (57.1%). Although a few physicians (4.4%) always performed IAC and some (10.7%) never did, most physicians made different decisions according to infarct size and presence of hemorrhagic transformation (HTr): IAC was performed more often in cases with medium-sized or small infarct than large one (68.2% vs. 35.9%, P<0.001), and in cases without HTr (68.6% vs. 34.9%, P<0.001). The most common method of administration was 'heparin followed by warfarin' (68.2%), and then 'warfarin alone' or 'warfarin with aspirin'. If IAC was not commenced, it resumed most commonly between 1 and 2 weeks after the onset (44.0%). CONCLUSION: Quite many neurologists in Korea did IAC in selective ACES, e.g. small sized infarction without HTr. Further studies are needed to prove the efficacy of IAC therapy in this selective population.
Atrial Fibrillation
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Electronic Mail
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Heparin
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Infarction
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Korea
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Neurology
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Stroke
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Taurine
6.Role of intracellular taurine in monensin-induced Na+, Ca++ accumulation and mechanical dysfunction in isolated rat hearts.
Young Hoon KIM ; Jong Wan PARK ; Myung Suk KIM
The Korean Journal of Physiology and Pharmacology 1997;1(5):537-546
It has been postulated that the intracellular taurine is co-transported with Na+ down a concentration gradient and prevents the intracellular accumulation of sodium. It is therefore, expected that an elevated level of intracellular taurine prevents the sodium-promoted calcium influx to protect the cellular damages associated with sodium and calcium overload. In the present study, we evaluated the effects of intra- and extracellular taurine on the myocardial Na+ and Ca++ contents and the cardiac functions in isolated rat hearts which were loaded with sodium by monensin, a Na+/-ionophore. Monensin caused a dose-dependent increase in intracellular Na+ accompanied with a subsequent increase in intracellular Ca++ and a mechanical dysfunction. In this monensin-treated heart, myocardial taurine content was decreased with a concomitant increase in the release of taurine. The monensin-induced increases in intracellular Na+, Ca++ and depression of cardiac function were prevented in the hearts of which taurine content had been increased by high-taurine diet. Conversely, in the hearts of which taurine concentration gradient had been decreased by addition of taurine in the perfusate, the monensin-induced increases in Na+, Ca++ and functional depression were accelerated. These results suggest that taurine, depending on the intra-extracellular concentration gradient, can affect intracellular sodium and calcium concentrations, and that an increased intracellular taurine may play a role in protection of myocardial dysfunction associated with the sodium and calcium overload.
Animals
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Calcium
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Depression
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Diet
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Heart*
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Monensin
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Rats*
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Sodium
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Taurine*
7.Taurine inhibits M2 polarization of macrophages by promoting mitophagy.
Chengying CHEN ; Chunhua LAN ; Jianglang YUAN ; Xingxing KONG ; Li LAN ; Xinhang WANG ; Shengboxiaoji CHANG ; Cailing LU ; Xiyi LI ; Shen TANG
Chinese Journal of Cellular and Molecular Immunology 2023;39(6):488-493
Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy
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Taurine
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Macrophages/metabolism*
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Protein Kinases/metabolism*
;
RNA, Messenger
8.Metabolic profiling of endogenous bile acids: a novel method to assess hepatoprotective effect of Tanreqing capsule on carbon-tetrachloride-induced liver injury in rats.
Ying XU ; Ping-Ping ZHONG ; Yan-Yan TAO
Chinese Journal of Natural Medicines (English Ed.) 2018;16(4):271-283
Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
Alanine Transaminase
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blood
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Animals
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Aspartate Aminotransferases
;
blood
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Bile Acids and Salts
;
blood
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metabolism
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Biomarkers
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blood
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Carbon Tetrachloride
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pharmacology
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Chemical and Drug Induced Liver Injury
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drug therapy
;
metabolism
;
pathology
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Chromatography, Liquid
;
Drugs, Chinese Herbal
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chemistry
;
pharmacology
;
therapeutic use
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Female
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Liver
;
drug effects
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pathology
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Male
;
Mass Spectrometry
;
Metabolome
;
drug effects
;
Metabolomics
;
Rats
;
Rats, Wistar
;
Taurocholic Acid
;
blood
;
Taurodeoxycholic Acid
;
analogs & derivatives
;
blood
9.Taxol and Taurine Protect the Renal Tissue of Rats after Unilateral Ureteral Obstruction: A Stereological Survey.
Saied KARBALAY-DOUST ; Ali NOORAFSHAN ; Seyed Mohammad POURSHAHID
Korean Journal of Urology 2012;53(5):360-367
PURPOSE: Blockage of the urinary tract induces changes in renal structure including tubular dilatation or atrophy, tubular cell death, inflammatory processes, and progressive interstitial fibrosis with the loss of renal parenchyma. The present study was conducted to survey the protective effects of Taxol and taurine on the renal structure after unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: UUO was induced in three groups of rats (n=6) who then received distilled water, Taxol (0.3 mg/kg/d), or taurine (7.5 mg/kg/d). Stereological methods were used to gather quantitative as well as comparative data. RESULTS: Less than -8% of the volume of the glomeruli, proximal convoluted tubules (PCT), distal convoluted tubules (DCT), Henle's loop, and collecting ducts were preserved after UUO. After treatment of the UUO rats with Taxol, between -32% and 88% of the parameters mentioned above remained intact, and after treatment of the UUO rats with taurine, between -16% and 46% of the parameters remained intact (p<0.01). Compared with the untreated UUO animals, the volume of necrotic and fibrotic tissues decreased -53% and -63% in the UUO rats treated with Taxol and taurine, respectively (p<0.01). Less than -3% of the lengths of the renal tubules (PCT, DCT, Henle's loop, and collecting) were preserved in the UUO rats. After treatment with Taxol and taurine, -61% to 70% and -43% to 53% of the length of the renal tubules were preserved, respectively (p<0.01). CONCLUSIONS: Taurine and Taxol are effective in preventing some structural renal damage in a direct ureteral obstruction model. Taxol was more effective in renal protection.
Animals
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Atrophy
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Cell Death
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Dilatation
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Fibrosis
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Kidney
;
Paclitaxel
;
Rats
;
Taurine
;
Ureter
;
Ureteral Obstruction
;
Urinary Tract
;
Water
10.Alcohol and brain health: from mechanisms to interventions.
Jung Ah MIN ; Dai Jin KIM ; Chang Uk LEE
Journal of the Korean Medical Association 2010;53(12):1115-1123
Alcohol-related problems are prevalent and lead to substantial economic, physical, and psychological burden. Among the various effects of alcohol, the effect on the brain is a matter of importance. The brain controls drinking behaviors and may be damaged earlier than other organs by alcohol. Moreover, alcohol-related brain pathologies are difficult to treat once they have progressed. Therefore, we overviewed the mechanisms and results of alcohol-induced brain damage and interventions against it in this article. Alcohol exerts neurotoxic effects mediated by various mechanisms, such as acetaldehyde toxicity, glutamate excitotoxicity, increased oxidative stress, and chronic inflammatory responses. In both functional and structural neuroimaging studies, the evidence of alcohol-induced brain damage was observed in various regions of gray and white matter. Brain damage has been known to be more prominent when it begins during the period of brain development and in women. Symptomatically, alcohol hangovers and alcohol-induced blackouts, which are highly prevalent alcohol-related problems, have been suggested to be early signs of alcohol-related brain damage. However, neurological changes induced by alcohol have been reported to be partly recovered by abstinence. The development of effective interventions would be clinically important. Although following the rules of low-risk drinking and abstinence have been the primary approaches up to the present, studies on mechanism-based neuroprotective interventions, such as acamprosate and memantine, have attempted. Further prospective and well-designed studies of neuroprotective interventions against neurotoxic effects of alcohol are required.
Acetaldehyde
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Brain
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Drinking
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Drinking Behavior
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Female
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Glutamic Acid
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Humans
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Memantine
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Neuroimaging
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Oxidative Stress
;
Taurine