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1.
Obes Facts ; 17(3): 255-263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38342095

RESUMO

INTRODUCTION: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. RESULTS: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. CONCLUSIONS: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.


Assuntos
Índice Vascular Coração-Tornozelo , Gordura Intra-Abdominal , Lipase Lipoproteica , Obesidade Mórbida , Gordura Subcutânea , Humanos , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Lipase Lipoproteica/sangue , Pessoa de Meia-Idade , Masculino , Feminino , Gordura Subcutânea/metabolismo , Obesidade Mórbida/cirurgia , Obesidade Mórbida/genética , Obesidade Mórbida/metabolismo , Obesidade Mórbida/sangue , Estudos Retrospectivos , Adulto , Japão , Gordura Intra-Abdominal/metabolismo , Índice de Massa Corporal , RNA Mensageiro/metabolismo , Gastrectomia , Rigidez Vascular , População do Leste Asiático
2.
Intern Med ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37981304

RESUMO

In recent years, lesbian, gay, bisexual, and transgender (LGBT) populations have been gaining acceptance in society. However, very few cases of malignancy in the LGBT population have been reported thus far. We herein report a transgender woman receiving estrogen supplementation who developed primary mediastinal large B-cell lymphoma (PMBCL) and was treated with dose-adjusted EPOCH-rituximab (DA-EPOCH-R) therapy. The patient achieved complete remission after the sixth course of DA-EPOCH-R therapy. To help this LGBT patient continue receiving chemotherapy smoothly on admission, adjusting the hospital environment, such as the allocation of rooms, was essential.

3.
J Food Biochem ; 46(12): e14482, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36219767

RESUMO

Aged garlic extract (AGE) has been shown to protect the skin against UV-induced damage, but effects of its volatile components remain unknown. We investigated the effects of the volatile fraction of AGE on the responses of cultured skin fibroblasts subjected to UV-B irradiation. UV-B irradiation (20 mJ/cm2 ) reduced the cell viability to 55% of control. The nonvolatile and volatile fractions of AGE inhibited the UV-B-induced reduction of cell viability; the cell viabilities were 100% and 73%, respectively. The volatile fraction inhibited the UV-B-induced increase in apoptotic cell death by 28%. The volatile fraction also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) induced by UV-B irradiation. GC-MS analysis revealed that a large number of volatile compounds were generated during aging of garlic. These results suggest that the volatile fraction of AGE has protective effects against the UV-B-induced death of skin fibroblasts, and that this effect may partly be due to an inhibition of apoptosis via the downregulation of MAPK signaling. The volatile compounds of AGE may have beneficial applications for skin health. PRACTICAL APPLICATIONS: In this study, we investigated the effects of AGE against cell damage of UV-B-irradiated human skin fibroblasts. The aging process of garlic produced characteristic volatile compounds that have significant protective effects against UV-induced cell damage. Our results demonstrated that the aging process is a suitable method to develop added value in garlic extracts to improve skin health.


Assuntos
Alho , Humanos , Idoso , Pele , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Antioxidantes/farmacologia , Fibroblastos , Apoptose , Raios Ultravioleta/efeitos adversos
4.
Obes Facts ; 15(3): 373-383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35016181

RESUMO

INTRODUCTION: Bariatric surgery (BS) has beneficial effects on body weight and type 2 diabetes. However, 44-52%, 20-40%, and 19-25% of patients with type 2 diabetes who undergo sleeve gastrectomy, sleeve gastrectomy with duodenal-jejunal bypass, and Roux-en-Y gastric bypass, respectively, show insufficient improvement 1 year after BS. It is thus important to predict the improvement in type 2 diabetes before BS. Many hormones are related to hyperglycemia. However, the relationship between hormones and improvement in type 2 diabetes after BS has not been studied. We aimed to evaluate the relationship between the improvement in type 2 diabetes and hormones in patients with obesity and type 2 diabetes who underwent BS. METHODS: We retrospectively reviewed 79 patients with obesity and type 2 diabetes who underwent BS, with a follow-up period of 12 months. We analyzed the relationship between some clinical parameters and complete remission (CR) of type 2 diabetes after BS. Patients were divided into two groups (type 2 diabetes CR and non-CR). Multiple regression analysis was performed to determine the parameters associated with type 2 diabetes resolution after BS. RESULTS: BS significantly improved body weight and glucose metabolism. Preoperative liver function, glycated hemoglobin (HbA1c), insulin secretion (homeostatic model assessment [HOMA]2-%B), renin activity, plasma aldosterone level, and duration of type 2 diabetes were significantly different between the CR and non-CR groups. Multiple regression analysis showed that preoperative HbA1c, HOMA2-%B, aldosterone concentration, and duration of type 2 diabetes were predictors of CR of type 2 diabetes after BS. Plasma aldosterone was the strongest predictor. DISCUSSION/CONCLUSION: Preoperative plasma aldosterone levels were related to the CR of type 2 diabetes after BS. Measuring plasma aldosterone levels preoperatively is useful for predicting the CR of type 2 diabetes after BS.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Aldosterona , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Hemoglobinas Glicadas/metabolismo , Humanos , Obesidade/complicações , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Eur J Clin Pharmacol ; 78(1): 77-87, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34410448

RESUMO

PURPOSE: Serum nivolumab concentrations exhibit a large variation in cancer patients. Cancer cachexia inducing systemic inflammation promotes the elimination of endogenous proteins, while its association with serum nivolumab remains unclear. The present study aimed to evaluate the impacts of cachexia progression in addition to blood components on serum nivolumab in cancer patients. METHODS: Thirty-eight non-small-cell lung cancer or renal cell cancer patients receiving biweekly intravenous nivolumab were enrolled. Blood samples were collected just before dosing at the 7th administration of nivolumab or later. Serum nivolumab together with serum proteins, inflammatory markers, and peripheral blood leukocytes were determined. Cancer cachexia was classified using the Glasgow Prognostic Score (GPS). Immune-related adverse events (irAEs) were monitored during the study period. RESULTS: Cancer patients had a large variation in serum nivolumab concentrations (interquartile range, 12-21 µg/mL per mg/kg). The serum nivolumab concentration was positively correlated with serum albumin, while negatively associated with serum globulin and immunoglobulin G (IgG). A negative correlation was observed between serum nivolumab and blood lymphocytes. Regarding cachexia progression, the patients with GPS 2 had a higher serum interleukin-6 concentration and a lower serum nivolumab concentration than those with GPS 0 or 1. The GPS, serum IgG, and blood lymphocytes were identified as independent variables for serum nivolumab. The incidence of irAEs was not associated with the nivolumab dose or serum nivolumab. CONCLUSION: Cachexia progression had a negative impact on serum nivolumab in cancer patients. The interindividual variation in serum nivolumab was characterized by cachexia progression in addition to blood components.


Assuntos
Antineoplásicos Imunológicos/sangue , Caquexia/etiologia , Caquexia/metabolismo , Neoplasias/complicações , Nivolumabe/sangue , Idoso , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Imunoglobulina G/metabolismo , Mediadores da Inflamação/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Nivolumabe/farmacocinética , Nivolumabe/uso terapêutico , Estudos Retrospectivos
6.
J Chemother ; 34(4): 258-263, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34661507

RESUMO

An increased risk for atherosclerosis has been noted in cancer survivors; however, studies that focus on the risk of atherosclerosis in patients treated with chemotherapy are scarce. Therefore, we evaluated 32 patients who received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy for B-cell malignant lymphoma by analysing the changes in atherosclerosis. Just before each treatment course, plasma levels of von Willebrand Factor (vWF) activity were evaluated, and carotid ultrasonography was performed at baseline and after the final treatment. Throughout the follow-up period, plasma vWF levels showed significantly transient increased by approximately 20%-40%. Both mean carotid intima-media thickness (IMT) and plaque score (PS) significantly increased during the 36.6 ± 26.0 weeks of observation (mean IMT: 0.724 ± 0.118 to 0.767 ± 0.129 mm; PS: 4.31 ± 3.53 to 4.87 ± 3.88, P < 0.001). Our study suggests that R-CHOP therapy promotes atherosclerosis.


Assuntos
Aterosclerose , Linfoma de Células B , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aterosclerose/induzido quimicamente , Espessura Intima-Media Carotídea , Ciclofosfamida , Doxorrubicina/efeitos adversos , Humanos , Prednisolona , Prednisona , Rituximab/efeitos adversos , Resultado do Tratamento , Vincristina/efeitos adversos , Fator de von Willebrand/análise
7.
Obes Facts ; 14(6): 641-649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34649248

RESUMO

INTRODUCTION: We previously reported that preoperative serum insulin-like growth factor-1 (IGF-1) is a predictor of total weight loss percentage (%TWL) after laparoscopic sleeve gastrectomy (LSG). IGF-1 may suppress muscle loss after surgery. IGF-1 almost accurately reflects the growth hormone (GH) secretion status, and GH has lipolytic effects. Therefore, IGF-1 may influence both the maintenance of skeletal muscle and the reduction of adipose tissue after LSG. The identification of the relationship between preoperative serum IGF-1 and body composition changes after LSG can help in understanding the pathophysiology of obesity. METHODS: We retrospectively reviewed 72 patients with obesity who underwent LSG and were followed up for 12 months. We analyzed the relationship between preoperative serum IGF-1 levels and body composition changes after LSG. A multiple regression model was used. RESULTS: LSG led to a significant reduction in body weight. Both body fat mass and skeletal muscle mass decreased after LSG. Preoperative serum IGF-1 levels significantly correlated with %TWL, changes in skeletal muscle mass, and body fat mass after LSG. The multiple regression model showed that preoperative serum IGF-1 levels were related to decreased body fat mass and maintaining skeletal muscle mass after LSG. DISCUSSION/CONCLUSION: Preoperative IGF-1 measurement helps predict not only successful weight loss but also decreases body fat mass and maintains skeletal muscle mass after LSG.


Assuntos
Laparoscopia , Obesidade Mórbida , Composição Corporal , Índice de Massa Corporal , Gastrectomia , Humanos , Fator de Crescimento Insulin-Like I , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
Obes Facts ; 14(6): 613-621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34649255

RESUMO

INTRODUCTION: In patients with severe obesity, albuminuria can be improved by both conventional medical therapy and bariatric surgery. The purpose of this study was to compare the impact of weight loss achieved through conventional medical therapy or laparoscopic sleeve gastrectomy (LSG) on albuminuria in Japanese subjects with severe obesity and identify the factors involved. METHODS: We retrospectively evaluated the clinical characteristics including the urinary albumin/creatinine ratio (UACR) of 340 consecutive subjects with a body mass index ≥35 who received LSG (n = 242) or medical therapy (n = 98) between 2010 and 2018 and were followed for at least 12 months. RESULTS: The baseline of the UACR was not different between the 2 groups. At the 12-month follow-up, total weight loss (TWL) and decreases in glycosylated hemoglobin (HbA1c) and loge UACR were greater in the LSG group than in the medical therapy group (body weight; -35.7 kg vs. -8.0 kg, p < 0.001, HbA1c; -1.4% vs. -0.7%, p < 0.001, loge UACR; -0.3 vs. 0.9, p < 0.001). The rate of complete remission of diabetes was significantly higher in the LSG group than in the medical therapy group. At 12 and 36 months (n = 111 in the medical therapy group, n = 56 in the LSG group at 36 months), loge UACR increased in the medical therapy group, while it remained unchanged or decreased in the LSG group. In subjects with microalbuminuria and macroalbuminuria, changes in the loge UACR correlated with percent total body weight loss (%TWL) in both groups at 12 months. Percent TWL contributed independently to the change in the loge UACR, irrespective of whether LSG was performed. In receiver-operating characteristic analysis, a weight loss of 7.8% predicted a decrease in the UACR (∆UACR <0 at 12 months). CONCLUSION: Our analysis suggests that albuminuria may increase over time if only medical therapy is continued. To improve albuminuria, weight loss may be more important than whether LSG is performed.


Assuntos
Laparoscopia , Obesidade Mórbida , Albuminas , Índice de Massa Corporal , Gastrectomia , Humanos , Japão , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
9.
Obes Facts ; 14(6): 633-640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34634786

RESUMO

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) significantly increases high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL) in pre-heparin serum (pre-heparin LPL levels). LPL is a regulator of serum triglyceride (TG) and HDL-C production; this may be the mechanism for HDL-C increase after LSG. This study aimed to elucidate the mechanism of increase in HDL-C levels by examining the relationship between changes in serum HDL-C levels and LPL after LSG. METHODS: We retrospectively reviewed 104 obese patients, who underwent LSG and were followed up for 12 months. We analyzed the relationship between changes in serum HDL-C levels and various clinical parameters after LSG. RESULTS: A significant decrease was observed in the patients' BMI and serum TG levels after LSG. Conversely, HDL-C levels and pre-heparin LPL levels were significantly increased after LSG. Simple linear regression showed that changes in HDL-C levels were significantly correlated with total weight loss percentage, change in TG levels, abdominal fat areas, and pre-heparin LPL levels. Additionally, the multiple regression model revealed that a decrease in TG levels and an increase in pre-heparin LPL levels were correlated with increased HDL-C levels after LSG. DISCUSSION/CONCLUSION: These results show that a decrease in TG levels and an increase in LPL are mechanisms for increased HDL-C levels after LSG.


Assuntos
Laparoscopia , Lipase Lipoproteica , HDL-Colesterol , Gastrectomia , Humanos , Lipase , Estudos Retrospectivos , Triglicerídeos
10.
J Agric Food Chem ; 69(3): 1020-1026, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33448852

RESUMO

The aroma of aged garlic extract (AGE) has been recently characterized as a complexity of seasoning-like, metallic, fatty, and acidic notes; most of the important aroma compounds were identified in a previous study. Besides the 25 previously identified aromas of AGE, several of the odor compounds that contribute to the acidic notes were isolated and identified using various analytical techniques, including gas chromatography coupled with an olfactometry monitoring system (GC-O), accurate and high-performance preparative GC system, GC-MS analysis, and sensory evaluation. The identified aromas include: 2,4-dimethyl-1,3-dithiolane, 2,5-dimethyl-1,4-dithiane, and 2,6-dimethyl-1,4-dithiane. Interestingly, AGE contains all stereoscopic isomers of each of these components. An aroma recombinant composed of the newly identified acidic odors with other key odorants showed good agreement with the aroma of AGE.


Assuntos
Alho/química , Compostos Heterocíclicos/química , Odorantes/análise , Compostos de Enxofre/química , Compostos Orgânicos Voláteis/química , Aromatizantes/química , Cromatografia Gasosa-Espectrometria de Massas , Olfatometria , Fatores de Tempo
11.
Oncol Lett ; 19(6): 3775-3780, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382329

RESUMO

The current study aimed to evaluate the relationship between 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET-CT) standardized uptake value (SUV) [pre-treatment SUV (pre-SUV) and post-treatment SUV (post-SUV)] and treatment results in patients with advanced oral cancer treated with superselective intra-arterial chemoradiotherapy (SSIACRT). A total of 37 patients with advanced oral cancer were treated with SSIACRT. The treatment consisted of superselective intra-arterial chemotherapy (docetaxel (DOC) 40 mg/mm2 and nedaplatin (CDGP) 80 mg/mm2) and concurrent radiotherapy (60-70 Gy) for a period of seven weeks. Pre-SUV and post-SUV of the primary tumor were measured. Overall survival (OS) and local control (LC) rates were selected as endpoints to evaluate prognosis. The median follow-up was 40 months (range 6-112 months). The 5-year OS and LC rates were 64.5 and 85.5%, respectively, and SSIACRT achieved high LC rate even in advanced oral cancers. In the log-rank test, post-SUV was a significant prognostic factor for OS and LC rates. The results of the current study demonstrated that SSIACRT is a reliable treatment with respect to survival in advanced oral cancer and post-SUV was a significant prognostic factor for OS and LC rates.

12.
Exp Ther Med ; 19(2): 1585-1593, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32010343

RESUMO

Garlic is used as a spice in cooking due to its unique aroma. The unique aroma of garlic has attracted considerable attention from scientists. The cloves contain large amounts of sulfur-based substances, which as a consequence of their reactive properties, are converted easily to a variety of volatile compounds during processing. The volatile profiles of processed garlic are influenced by processing conditions, such as temperature, pH and solvent. Numerous studies on these changes in volatile compounds that occur during processing have been reported, with a number of types of sulfur-containing volatile compounds being identified in fresh and processed garlic. This review summarizes the volatile components of fresh and processed garlic, particularly those produced by heating and aging. The pungent odor of fresh garlic is contributed mainly to thiosulfinates and their degradation products. During the heating process of garlic, thiosulfinates are mainly decomposed, and nitrogen-containing volatile compounds, such as pyridines and pyrazines are generated. Aldehydes are dominant compounds in black garlic, while esters and phenols are key aroma compounds in aged garlic extract. The slight variations in chemical reactions during the aging process may lead to differences in the aroma of the two types of garlic.

13.
Food Chem ; 312: 126081, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901831

RESUMO

We analyzed the aroma of aged garlic extract (AGE) using a sensomics approach to elucidate the effect of the aging process on AGE aroma. Sensory analysis showed a high intensity of the "acid", "seasoning," and "metallic" odor in AGE. The aroma of AGE exhibited more complex notes compared to those of fresh garlic which were characterized as "pungent." Aroma components of AGE were evaluated using aroma extract dilution analysis. Thirty-nine odorants were detected as key odorants in AGE. Allyl methyl sulfide (sulfury), 2-methoxyphenol (smoky), 4,5-dimethyl-3-hydroxy-2(5H)-furanone (seasoning-like), eugenol (spicy) and ethyl butanoate (fruity), which were mostly absent in fresh garlic, contributed to the AGE aroma. These results suggest that chemical reactions that occur during the aging process of garlic are important for the development of the characteristic aroma of AGE.


Assuntos
Alho/química , Odorantes/análise , Extratos Vegetais/química , Técnicas de Diluição do Indicador , Fatores de Tempo , Compostos Orgânicos Voláteis/análise
14.
Clin Chim Acta ; 468: 187-194, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28274611

RESUMO

Administration of pivalate-containing antibiotics decreases serum carnitine and increases urinary pivaloylcarnitine, resulting in hypocarnitinemia. Carnitine and acylcarnitines are important biomarkers in the diagnosis of carnitine deficiency, but the relationship between acylcarnitines and drug-induced hypocarnitinemia remains unclear. Quantification of acylcarnitines enables discovery of new biomarkers for prediction and diagnosis of drug-induced hypocarnitinemia. Here we describe a liquid chromatography/tandem mass-spectrometric method for simultaneously quantifying carnitine, 15 acylcarnitines, and cefditoren (the pivoxilated product of an antibiotic prodrug) in human urine. The matrix effect is corrected in 87.8-103% using deuterium-labeled internal standards (2H9-carnitine, 2H3-hexanoylcarnitine, and 2H3-stearoylcarnitine). The surrogate matrix method had an error of <13% in comparison with a standard addition method. Dynamic ranges were 0.1-100µmol/l for acylcarnitines and 0.3-300µg/ml for cefditoren. Both accuracy and precision were <19.7% at the lower limit of quantification and <14.8% for other quality controls. In an example application of this method, urine samples from eight healthy volunteers (five adults and three children) were analyzed, and individual differences were clearly observed.


Assuntos
Carnitina/análogos & derivados , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Urinálise/métodos , Adulto , Calibragem , Carnitina/urina , Criança , Humanos , Reprodutibilidade dos Testes
15.
Artigo em Inglês | MEDLINE | ID: mdl-25375427

RESUMO

The driving mechanism and the swirl direction of the bathtub vortex are investigated by the linear stability analysis of the no-vortex flow as well as numerical simulations. We find that only systems having plane symmetries with respect to vertical planes deserve research for the swirl direction. The bathtub vortex appearing in a vessel with a rectangular cross section having a drain hole at the center of the bottom is proved to be induced by instability when the flow rate exceeds a threshold. The Coriolis force is capable of determining the swirl direction to be cyclonic.

16.
Inflamm Res ; 58(9): 593-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19333727

RESUMO

OBJECTIVE AND DESIGN: In this study, the possible protective effect of glycyrrhizin (GL), an active compound derived from licorice root, was examined on T cell-mediated liver injury in mice. MATERIALS AND METHODS: Mice were subjected to liver injury by intravenous injection of concanavalin A (Con A). They had been treated with GL (i.p.) 30 min before the injection. Liver injury was estimated by measuring serum levels of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), and by examining liver sections with hematoxylin-eosin staining. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein in the liver was determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Serum transaminases and hepatic iNOS levels increased with time after Con A treatment. Expression of iNOS mRNA in the liver was elevated for up to 8 h, and at 8 h, GL (ED(50): 10.5 mg/kg) suppressed the increases in AST and ALT in response to Con A. An increase in iNOS mRNA expression and protein was inhibited by treatment with GL. Furthermore, GL inhibited cell infiltration and the degeneration of hepatocytes in the liver of Con A-treated mice. CONCLUSION: The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas , Concanavalina A/toxicidade , Ácido Glicirrízico/farmacologia , Fígado , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Concanavalina A/imunologia , Humanos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/metabolismo , Linfócitos T/imunologia
17.
J Pharmacol Sci ; 108(1): 104-11, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18787303

RESUMO

We examined the mechanism of thrombin on proliferation of synovial fibroblasts obtained from rheumatoid arthritis (RA). Thrombin concentration-dependently induced proliferation of synovial fibroblasts. Proliferation in response to thrombin (10 U/ml) was completely blocked by hirudin. TP367 and TP508, peptides corresponding to 2 noncatalytic regions of thrombin, failed to induce cell proliferation. Thrombin did not induce the production of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) in synovial fibroblasts. Expression of proteinase-activated receptor (PAR)-1 and PAR-3 mRNAs was observed in synovial fibroblasts. Thrombin and PAR-1 agonist peptide (AP), but not PAR-3 AP, induced intracellular calcium mobilization. PAR-1 AP induced cell proliferation whereas PAR-3 AP and PAR-4 AP had no effect on proliferation. Pertussis toxin (PTX), a Gialpha protein inhibitor; wortmannin, a PI (phosphatidylinositol) 3-kinase inhibitor; and PD98059, a specific MEK [mitogen-activated protein (MAK) kinase kinase] inhibitor, inhibited the thrombin-induced cell proliferation. Furthermore, the proliferation of synovial fibroblasts was suppressed by U-73122, a PLC (phospholipase C) inhibitor; 2-APB, an antagonist of InsP3 (inositol 1,4,5-triphosphate) receptor; and GF-109203X, a PKC (protein kinase C) inhibitor. These results suggest that thrombin induces the proliferation of RA synovial fibroblasts through the activation of PAR-1, leading to the PTX-sensitive G proteins - PI3 kinase pathway and PTX-insensitive G proteins - PLC (InsP3 receptor) Ca(2+)-PKC branch.


Assuntos
Fibroblastos/efeitos dos fármacos , Hemostáticos/farmacologia , Receptor PAR-1/fisiologia , Líquido Sinovial/citologia , Trombina/farmacologia , Cálcio/fisiologia , Sinalização do Cálcio/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptor PAR-1/biossíntese , Receptores de Trombina/biossíntese , Receptores de Trombina/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Estimulação Química
18.
J Pharm Pharmacol ; 60(1): 91-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18251086

RESUMO

Glycyrrhizin, a biological active compound isolated from the liquorice root, has been used as a treatment for chronic hepatitis. We have examined the involvement of matrix metalloproteinase (MMP)9 in the development of lipopolysaccharide (LPS) and D-galactosamine (GalN)-induced liver injury in mice. We also investigated the effect of glycyrrhizin on expression of MMP-9 in this model. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased after LPS/ GalN treatment. Expression of MMP-9 mRNA and protein was markedly up-regulated in liver tissues 6-8 h after LPS/GalN treatment. Pretreatment with glycyrrhizin (50 mg kg(-1)) and the MMP inhibitor (5 mg kg(-1)) suppressed increases in serum levels of ALT and AST in mice treated with LPS/GalN. Furthermore, glycyrrhizin inhibited levels of both mRNA and protein for MMP-9. Immunohistochemical reaction for MMP-9 was observed in macrophages/monocytes infiltrated in the inflammatory area of liver injury. Glycyrrhizin reduced the infiltration of inflammatory cells and immunoreactive MMP- 9 in liver injury. The results indicated that MMP-9 played a role in the development of LPS/GalN- induced mouse liver injury, and suggested that an inhibition by glycyrrhizin of the acute liver injury may have been due to a down-regulation of MMP-9.


Assuntos
Ácido Glicirrízico/farmacologia , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Doença Aguda , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Galactosamina/administração & dosagem , Galactosamina/toxicidade , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/uso terapêutico , Imuno-Histoquímica , Injeções Intraperitoneais , Injeções Intravenosas , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/toxicidade , Fígado/metabolismo , Fígado/patologia , Hepatopatias/sangue , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
19.
Arch Histol Cytol ; 71(3): 163-78, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19194039

RESUMO

The inhibition of apoptosis by glycyrrhizin (GL) in hepatic injury induced by injection of lipopolysaccharide (LPS)/D-galactosamine (D-GalN) was examined in the present study. Morphological and biochemical analyses of LPS/D-GalN-induced mouse liver injury revealed that apoptosis occurred exclusively in injured hepatocytes of the centrilobular area. The degree of hepatic injury was associated with a substantial number of hepatocytes undergoing apoptosis. Transaminase levels were significantly increased at 6 to 8 h after the injection of LPS/D-GalN compared with controls. GL inhibited the elevation of serum transaminase levels when it was given to mice at 30 min before the administration of LPS/D-GalN. Morphological analyses using the TUNEL-method showed GL significantly reduced the number of TUNEL-labeled cells in acute hepatitis induced with LPS/D-GalN-treatment. Cells from the pericentral hepatic injury region were dissected out using a microdissection-method, and the DNA-ladder was clearly documented. Furthermore, results obtained through the TUNEL-method were confirmed with an oligonucleosome-bound DNA ELISA. From the current results, it seems reasonable to conclude that the protective role of GL in LPS/D-GalN-induced liver injury is performed through the inhibition of hepatic apoptosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ácido Glicirrízico/uso terapêutico , Animais , Caspases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galactosamina/administração & dosagem , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Imuno-Histoquímica , Injeções , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Tempo
20.
Eur J Pharmacol ; 576(1-3): 136-42, 2007 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-17825282

RESUMO

The effects of glycyrrhizin isolated from licorice root were investigated on acute hepatitis induced by lipopolysaccharide (LPS) and d-galactosamine in mice. Serum alanine aminotransferase (ALT) activity was markedly increased 6 h to 8 h after administration of LPS/d-galactosamine. Levels in serum of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10 and IL-12 reached a maximum by 2 h, whereas levels of IL-18, as well as of ALT, were maximal at 8 h. Glycyrrhizin (ED(50): 14.3 mg/kg) inhibited the increase in ALT levels when it was given to mice at 30 min before administration of LPS/d-galactosamine. Inflammatory responses, including infiltration of neutrophils and macrophages in the liver injury, were modulated by glycyrrhizin. Increases in ALT levels were reduced by an administration of glycyrrhizin at 10 min and 60 min but not 3 h, even after LPS/d-galactosamine treatment. However, glycyrrhizin had no effect on the production of TNF-alpha, IL-6, IL-10 and IL-12, whereas it significantly inhibited IL-18 production. Exogenous IL-18 further increased the elevation in ALT levels in mice treated with LPS/d-galactosamine. Glycyrrhizin completely suppressed the effect of IL-18 of increasing ALT levels. IL-18 was detected by immunohistochemistry in inflammatory cells such neutrophils and macrophages in liver injury. Glycyrrhizin reduced the responsiveness of cells to IL-18 in the liver injury. These results suggest that glycyrrhizin inhibits the LPS/d-galactosamine-induced liver injury through preventing inflammatory responses and IL-18 production. Furthermore, it seems that glycyrrhizin prevents IL-18-mediated inflammation in liver injury.


Assuntos
Ácido Glicirrízico/uso terapêutico , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/sangue , Animais , Doença Hepática Induzida por Substâncias e Drogas , Citocinas/sangue , Galactosamina , Lipopolissacarídeos , Hepatopatias/sangue , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
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