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1.
J Immunol ; 184(9): 5253-62, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20368270

RESUMO

MCP1 is upregulated by various stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular mechanisms of transcriptional regulation of the MCP1 gene under hyperosmolar conditions are poorly understood. Treatment of NRK52E cells with NaCl or mannitol resulted in significant elevation of MCP1 mRNA and protein in a time- and dose-dependent manner. Treatment with a p38MAPK inhibitor (SB203580), an ERK inhibitor (PD98059), or an MEK inhibitor (U0126), suppressed the increase in MCP1 expression caused by hypertonic NaCl, whereas a JNK inhibitor (SP600125) and an AP1 inhibitor (curcumin) failed to attenuate MCP1 mRNA expression by NaCl. In the 5'-flanking region of the MCP1 gene, there is a sequence motif similar to the consensus TonE/ORE as well as the consensus C/E binding protein (BP), NF-kappaB, and AP1/Sp1 sites. Luciferase activity in cells transfected with reporter constructs containing a putative TonE/ORE element (MCP1-TonE/ORE) enhanced reporter gene expression under hypertonic stress. Results of electrophoretic gel mobility shift assay showed a slow migration of the MCP1-TonE/ORE probe, representing the binding of TonEBP/OREBP/NFAT5 to this enhancer element. These results indicate that the 5'-flanking region of MCP1 contains a hypertonicity-sensitive cis-acting element, MCP1-TonE/ORE, as a novel element in the MCP1 gene. Furthermore, p38MAPK and MEK-ERK pathways appear to be, at least in part, involved in hypertonic stress-mediated regulation of MCP1 expression through the MCP1-TonE/ORE.


Assuntos
Quimiocina CCL2/genética , Elementos Facilitadores Genéticos/imunologia , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , Fatores de Transcrição/fisiologia , Regiões 5' não Traduzidas/imunologia , Animais , Linhagem Celular , Quimiocina CCL2/biossíntese , Sequência Consenso/imunologia , Elementos Facilitadores Genéticos/genética , Regulação Enzimológica da Expressão Gênica/imunologia , Soluções Hipertônicas/farmacologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Fatores de Transcrição NFATC/metabolismo , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
2.
Phys Chem Chem Phys ; 12(13): 3156-63, 2010 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-20237704

RESUMO

Effects of metal substrate on the bonding nature of isocyanide group of two aryl isocyanides, 1,4-phenylene diisocyanide (PDI) and 4-methylphenyl isocyanide (MPI), and tilt angle of MPI were examined by measuring sum frequency generation (SFG) spectra of the self-assembled monolayers (SAMs) of these molecules on Au, Pt, Ag, and Pd surfaces. The SFG peaks due to "metal bonded" and "free"-NC groups were resolved by comparing the SFG spectra of PDI with IR spectra obtained by DFT calculations and previous results of vibrational spectroscopy. Based on the peak positions of the "metal bonded"-NC, it is clarified that while PDI and MPI were adsorbed at top sites on Au, Ag, and Pt surfaces, they adsorbed at bridge sites on the Pd surface. The tilt angles of MPI were determined from the intensity ratio between the SFG peaks of C-H symmetric and asymmetric stretching vibrational modes of the CH(3) group. The tilt angles of the MPI SAMs were in the order of Pt < Pd < Ag < Au, reflecting the bonding nature between the -NC group and the substrate atoms.

3.
Biol Pharm Bull ; 33(2): 223-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20118544

RESUMO

The present study was designed to clarify the effects of an ethanol extract of artichoke leaf on acute gastric mucosal injury in rats. Oral administration of artichoke leaf extract dose-dependently prevented absolute ethanol-induced (125-500 mg/kg) or restraint plus water immersion stress-induced gastric mucosal injury (1000-2000 mg/kg). The artichoke leaf extract contains 1% cynaropicrin and 0.8% chlorogenic acid as main components and 70% dextrin as a vehicle. Cynaropicrin at doses of 1/100 of artichoke leaf extract [ethanol-induced mucosal injury: 5 mg/kg, per os (p.o.); stress-induced mucosal injury: 20 mg/kg, p.o.] also prevented gastric mucosal injury in both animal models. However, dextrin and chlorogenic acid at doses contained in the leaf extract were ineffective in both models. When artichoke leaf extract was given orally to normal rats, it (500-2000 mg/kg, p.o.) dose-dependently increased gastric mucus content. In addition, it (125-500 mg/kg, p.o.) dose-dependently prevented the decrease in gastric mucus content by absolute ethanol. When the effects of artichoke leaf extract on basal gastric acid secretion in rats were evaluated, it (500-2000 mg/kg, p.o.) dose-dependently increased the volume of gastric juice in normal rats. However, it was ineffective in decreasing basal gastric acid secretion in normal rats. These results indicate that artichoke leaf extract is effective against acute gastritis and its beneficial effect is due to that of cynaropicrin. The gastric mucus-increasing action of artichoke leaf extract may be, at least in part, related to the anti-gastritic action of the extract.


Assuntos
Antiulcerosos/uso terapêutico , Cynara scolymus , Mucosa Gástrica/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Doença Aguda , Animais , Antiulcerosos/isolamento & purificação , Cynara scolymus/química , Cynara scolymus/fisiologia , Suco Gástrico/efeitos dos fármacos , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/tratamento farmacológico , Gastrite/patologia , Masculino , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Ratos , Ratos Sprague-Dawley
4.
Biol Pharm Bull ; 33(6): 963-70, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20522960

RESUMO

In an acute treatment experiment, metformin (150, 300 mg/kg, per os (p.o.)) markedly reduced the consumption of a high-fat diet (HFD) (45 kcal% fat-containing diet) for 2 h after the HFD was given to the fasted male C57BL/6J (B6) mice. In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given. On the other hand, pioglitazone (12 mg/kg, p.o.) slightly increased the food intake but did not affect active GLP-1 levels when given at 6 and 12 mg/kg, p.o. In a long-team experiment for 9 weeks, metformin treatment (0.25, 0.5% in the HFD) resulted in reduction of body weight gain and HFD intake. When wet weights of various body fat pads of each mouse were measured at 9 weeks after treatment, metformin markedly decreased these weights. However, pioglitazone treatment (0.01, 0.02% in the HFD) did not have obvious effects on these parameters. Oral glucose tolerance test was carried out after 20-h fasting at 4 weeks post-treatment. Whereas metformin treatment (0.25, 0.5%) markedly improved glucose intolerance, pioglitazone treatment (0.02%) slightly improved this parameter. At 9 weeks, both metformin and pioglitazone markedly improved hyperglycemia and hyperinsulinemia. Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective. These results indicate that metformin reduces body weight gain and improves glucose intolerance in HFD-induced obese diabetic B6 mice.


Assuntos
Ingestão de Energia/efeitos dos fármacos , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/sangue , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperinsulinismo/sangue , Hiperinsulinismo/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/sangue , Leptina/sangue , Masculino , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/fisiopatologia , Pioglitazona , Tiazolidinedionas/farmacologia
5.
Eur J Pharmacol ; 548(1-3): 174-80, 2006 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-16979162

RESUMO

We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on renal damage in streptozotocin-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after streptozotocin administration. Daily treatment with probucol, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium, and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals, when histopathological evaluation was performed at 4, 8 and 15 weeks (glomerular and mesangial hypertrophy was observed only at 15 weeks). Combined probucol and insulin treatment was the most effective in suppressing these renal histopathological changes. These results indicate that combined treatment with probucol and insulin is useful in preventing the progression of renal damage in diabetic rats. The possible mechanisms for the preventive effect of this combined treatment will be discussed.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/farmacologia , Nefropatias/tratamento farmacológico , Probucol/farmacologia , Albuminúria , Animais , Anticolesterolemiantes/farmacologia , Glicemia , Colesterol/sangue , Colesterol na Dieta , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Sinergismo Farmacológico , Quimioterapia Combinada , Hipoglicemiantes/farmacologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Peróxidos Lipídicos/urina , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue
6.
Biol Pharm Bull ; 29(6): 1110-9, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16755002

RESUMO

We have already reported that slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) is produced by a single i.p. injection of a subdiabetogenic dose (100 mg/kg) of streptozotocin (STZ) to 8-week-old male ICR mice. The aim of the present study was to clarify whether or not the progressive NIDDM is induced in ddY, BALB/c, C57BL/6 and ICR mice by the administration of STZ. Eight-week-old male mice of the 4 different strains were administered a single i.p. injection of STZ at various doses (ICR, ddY and BALB/c: 100-200 mg/kg; C57BL/6: 75-150 mg/kg). Among the ddY, BALB/c and C57BL/6 mice, a time course-related rise in non-fasting serum glucose levels throughout the observation period of 1-12 weeks after STZ administration was only induced in the 125 mg/kg STZ ddY and 100 mg/kg STZ ICR mice. In contrast with serum glucose levels, the area of islets and the percentage of the relative number of insulin-immunoreactive cells (beta-cells) to glucagon-immunoreactive cells (alpha-cells) in the 100 mg/kg STZ ICR and 125 mg/kg STZ ddY mice continued to decrease gradually over time. In addition, in low dose STZ mice of both strains, the insulin response to glucose stimulation was extremely impaired over time, although non-fasting serum insulin levels were maintained near normal levels. The rate of the progression of diabetes was faster in the 125 mg STZ ddY mice than in the 100 mg/kg STZ ICR mice.


Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Camundongos , Estreptozocina/toxicidade , Animais , Glicemia/análise , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/urina , Ingestão de Líquidos , Ingestão de Alimentos , Teste de Tolerância a Glucose , Imuno-Histoquímica , Injeções Intraperitoneais , Insulina/sangue , Masculino , Camundongos Endogâmicos , Especificidade da Espécie , Urina
7.
Hinyokika Kiyo ; 52(4): 265-70, 2006 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-16686353

RESUMO

The data of sexually transmitted urethritis in males have been collected at 24 institutes in Kyoto Prefecture since October, 2002. The data collected from January to December in 2004 are summarized herein. A total of 1,275 patients were diagnosed with urethritis during this period. Microbiological examinations isolated Neisseria gonorrhoeae alone in 368 (29%), Chlamydia tracomatis alone in 336 (26%), both in 85 (7%), and others in 453 (36%). Male patients under 20 years old tended to have Chlamydial urethritis, alone or combined with gonococcal infection, and had a predominant infectious source, a non-commercial-sexual-worker female partner, suggesting a profound problem in sexual life of adolescents. The urologist preferred to use quinolones as the first therapeutic modality against male urethritis. However, drug resistance of N. gonorrhoeae, especially against quinolones, has rapidly progressed, which was also observed by a sensitivity examination test. Antibiotics should be used adequately against male urethrits according to the recent guidelines.


Assuntos
Parceiros Sexuais , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Uretrite/epidemiologia , Adolescente , Adulto , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neisseria gonorrhoeae/isolamento & purificação , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Uretrite/tratamento farmacológico
8.
Eur J Pharmacol ; 513(1-2): 159-68, 2005 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-15869753

RESUMO

We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on cataracts of streptozotocin-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after streptozotocin injection. Cataracts were observed from 8 weeks in untreated hypercholesterolemic and diabetic rats and the incidence of catarats increased to 100% by 15 weeks. The incidence of cataracts in rats treated with probucol, insulin and their combination was first seen at 12, 12 and 15 weeks, respectively, and was 86%, 63% and 33%, respectively, at 15 weeks. The preventive effects of both agents alone and their combination on the cataracts were confirmed by histopathological evaluation of eyeballs. The combined treatment with both agents markedly improved hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These results indicate that the combined treatment with probucol and insulin is useful in preventing the development and progression of diabetic cataracts.


Assuntos
Catarata/prevenção & controle , Colesterol na Dieta/administração & dosagem , Diabetes Mellitus Experimental/complicações , Insulina/farmacologia , Probucol/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Catarata/etiologia , Catarata/mortalidade , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Quimioterapia Combinada , Ingestão de Alimentos/efeitos dos fármacos , Olho/efeitos dos fármacos , Olho/patologia , Insulina/uso terapêutico , Peróxidos Lipídicos/sangue , Masculino , Probucol/uso terapêutico , Ratos , Ratos Sprague-Dawley , Taxa de Sobrevida , Fatores de Tempo , Triglicerídeos/sangue
9.
Int Immunopharmacol ; 24(2): 267-275, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25533502

RESUMO

Butein (3,4,2',4'-tetrahydroxychalcone), a flavonoid derivative, has been reported to show several biological actions, including anti-inflammatory and anti-cancer. However, the possible molecular mechanisms involved are poorly understood. Treatment of human umbilical vein endothelial cells (HUVECs) with butein significantly inhibited cell surface intercellular adhesion molecule-1 (ICAM-1) expression, ICAM-1 protein synthesis, and mRNA expression induced by tumor necrotic factor-α (TNF-α) and/or phorbol 12-myristate 13-acetate (PMA). Electrophoretic mobility shift assay revealed that butein blocked activation of transcription factors, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), induced by TNF-α and PMA. Moreover, butein abolished TNF-α- and PMA-induced IκBα phosphorylation, which participates in NF-κB activation, and PMA-induced phosphorylation of c-Jun, a subunit composed of AP-1. In vitro, butein inhibited the phosphorylation of c-Jun, binding to GST beads, mediated by JNK isolated from PMA-treated cells. The inhibitory action of butein on the JNK-mediated in vitro c-Jun phosphorylation was abrogated in the presence of ATP. These results indicate that in HUVECs, butein suppresses the expression of ICAM-1 mRNA and protein through the inhibition of the activation of NF-κB and AP-1 induced by TNF-α and PMA, that the inhibitory action of butein on NF-κB activation results from the inhibition of IκBα phosphorylation by IκB kinase (IKK), and that the inactivation of PMA-activated AP-1 by butein is due to the blocking of JNK-mediated c-Jun phosphorylation through the inhibition of ATP binding.


Assuntos
Anti-Inflamatórios/farmacologia , Chalconas/farmacologia , Células Endoteliais/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Células Cultivadas , Células Endoteliais/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas I-kappa B/metabolismo , Terapia de Imunossupressão , Molécula 1 de Adesão Intercelular/genética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/genética , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/imunologia , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Cordão Umbilical/citologia
10.
Eur J Pharmacol ; 444(3): 209-15, 2002 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-12063082

RESUMO

In this study, we compared the effects of cimetidine and omeprazole on the healing of acetic acid-induced gastric ulcers in 8-, 48-, and 96-week-old rats. The repeated oral administration of cimetidine or omeprazole for 14 consecutive days markedly accelerated the ulcer healing in 8- and 48-week-old rats. However, both drugs were ineffective in 96-week-old rats. The basal gastric acid secretion of 8-, 48-, and 96-week-old rats decreased with aging. A single oral administration of cimetidine or omeprazole strongly decreased basal gastric acid secretion in the three different ages of rats. Cimetidine and omeprazole produced a potent and sustained serum gastrin-elevating action in 8- and 48-week-old rats. However, the gastrin-elevating actions of both drugs in 96-week-old rats were much weaker than in the 8- and 48-week-old rats. These results indicate that cimetidine and omeprazole have potent gastric ulcer healing actions in 8- and 48-week-old rats, as well as potent serum gastrin-elevating actions, but both drugs are ineffective in 96-week-old rats, which have lost their gastrin-elevating actions.


Assuntos
Envelhecimento/fisiologia , Cimetidina/uso terapêutico , Omeprazol/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Gastrinas/sangue , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/sangue , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/fisiopatologia
11.
Yakugaku Zasshi ; 133(7): 773-82, 2013.
Artigo em Japonês | MEDLINE | ID: mdl-23811765

RESUMO

The aim of our study was to produce a new diabetic model by a single i.p. injection of various doses of streptozotocin (STZ) to 8-week-old male Institute of Cancer Research (ICR) mice. When STZ was i.p. injected at doses rainging from 75 to 200 mg/kg, in the group injected 200 mg/kg STZ, the non-fasting serum glucose levels markedly rose from 1 week after STZ administration and the high glucose levels were maintained for 9 weeks. The serum glucose levels in the group administered 100 mg/kg STZ were within a normal range at 1 week after STZ administration, but thereafter continued to increase gradually till 9 weeks. In contrast with the serum glucose levels, a marked reduction in the percentage of the relative numbers of ß-cells in the islets of pancreas from 1 week in mice injected 200 mg/kg STZ was observed. On the other hand, in 100 mg/kg STZ mice, the number of ß-cells was almost normal percentage at 1 week and then continued to gradually decrease as the time went on throughout 24-week-observation. These results indicate that only the 100 mg/kg STZ injection produces slowly progressive diabetes mellitus in mice. Low molecular weight (LMW) chitosan (chitosan lactate, average of molecular weight: 20000) was administered as drinking water from prediabetic stage (from 2 weeks after 100 mg/kg STZ injection). The 0.2% or 0.8% LMW chitosan administration prevented the progression of 100 mg/kg STZ-induced slowly progressive diabetes mellitus. The mechanisms, which LMW chitosan is effective in this model may be discussed on ß-cells.


Assuntos
Quitosana/uso terapêutico , Diabetes Mellitus Experimental/prevenção & controle , Modelos Animais de Doenças , Animais , Progressão da Doença , Masculino , Camundongos , Peso Molecular , Estreptozocina
12.
Biol Pharm Bull ; 32(2): 276-82, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19182389

RESUMO

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.


Assuntos
Progesterona/administração & dosagem , Supositórios , Resinas Acrílicas , Química Farmacêutica , Preparações de Ação Retardada , Composição de Medicamentos , Excipientes , Tamanho da Partícula , Pós , Dodecilsulfato de Sódio , Solubilidade
13.
Eur J Pharmacol ; 601(1-3): 143-7, 2008 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-18955044

RESUMO

In the present study, we compared the effects of alpha-tocopherol and probucol, antioxidants, on the healing of acetic acid-induced gastric ulcers in 8-, 48- and 96-week-old rats. The repeated oral administration of alpha-tocopherol (16 mg/kg twice daily) and probucol (1000 mg/kg twice daily) for 14 consecutive days markedly accelerated the gastric ulcer healing in 48- and 96-week-old rats as well as 8-week-old ones. The ulcer healing effects of both drugs were not significantly different among the rats at three different ages. The superoxide dismutase (SOD) activity in the ulcerated region of 8-, 48- and 96-week-old rats was markedly lower than that in the unulcerated region. In contrast, the thiobarbituric acid (TBA)-reactive substance content, an index of lipid peroxidation, in the ulcerated region of rats at three different ages markedly increased, as compared to that in the unulcerated region. The SOD activity tended to decrease with aging, while the TBA-reactive substance content gradually increased. The repeated administration of alpha-tocopherol and probucol accelerated the ulcer healing and inhibited the increase in the TBA-reactive substance content in the ulcerated region. These results suggest that alpha-tocopherol and probucol promote the ulcer healing by their potent antioxidant activities in 48- and 96-week-old rats as well as 8-week-old rats.


Assuntos
Antioxidantes/farmacologia , Probucol/farmacologia , Úlcera Gástrica/tratamento farmacológico , alfa-Tocoferol/farmacologia , Ácido Acético , Administração Oral , Envelhecimento , Animais , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/fisiopatologia , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
14.
J Clin Immunol ; 27(4): 409-29, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17516154

RESUMO

We investigated participation of monocyte chemoattractant protein-1 (MCP-1) in tubulointerstitial fibrosis and correlation between MCP-1 and proteinuria in Wistar-Kyoto (WKY) rats with glomerulonephritis induced by anti-glomerular basement membrane (anti-GBM) antibody. WKY rats showed marked proteinuria and severe glomerular crescent formation at 7 days post antibody injection. At 28 days, tubulointerstitial fibrotic lesions were observed, followed by sustained heavy proteinuria and severe tubulointerstitial fibrosis at 56 days. Histological examination revealed that the overlapped immunoreactivities of MCP-1, rat albumin, and p65NF-kappaB were detected in the same tubular segments of nephritic kidney, and a significant positive correlation was observed between proteinuria and MCP-1 expression in the tubulointerstitial fibrosis. ED-1- and CD8-positive cells were also abundant, and there was a good correlation between monocyte/macrophage recruitment and MCP-1 expression in the tubulointerstitial area. These results suggest that MCP-1 participates in the progression of tubulointerstitial fibrosis, through massive albuminuria, which is accompanied by marked monocyte/macrophage recruitment.


Assuntos
Doença Antimembrana Basal Glomerular/imunologia , Quimiocina CCL2/imunologia , Rim/imunologia , Nefrite Intersticial/imunologia , Proteinúria/imunologia , Animais , Doença Antimembrana Basal Glomerular/induzido quimicamente , Quimiocina CCL2/genética , Quimiocina CCL2/urina , Creatinina/sangue , Creatinina/urina , Modelos Animais de Doenças , Progressão da Doença , Fibrose/induzido quimicamente , Fibrose/imunologia , Fibrose/patologia , Regulação da Expressão Gênica , Rim/química , Rim/patologia , Masculino , Nefrite Intersticial/induzido quimicamente , Proteinúria/induzido quimicamente , Proteinúria/urina , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos WKY , Ratos Wistar , Especificidade da Espécie , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
15.
Biol Pharm Bull ; 29(11): 2206-13, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17077516

RESUMO

Oral administration of tea catechin dose-dependently prevented absolute ethanol-induced (50, 100, 200 mg/kg) or restraint plus water immersion stress-induced acute gastric mucosal injury (300, 400 mg/kg) in rats. When the effect of test compound was evaluated on the 15th day after acetic acid injection to rats, repeated oral administration of tea catechin (25, 50, 100 mg/kg twice daily) dose-dependently accelerated the healing of acetic acid-induced chronic gastric ulcers. Tea catechin (10(-5)-10(-1) g/100 ml) concentration-dependently scavenged superoxide anions in vitro. Tea catechin (100, 200 mg/kg orally) markedly inhibited the increase in thiobarbituric acid-reactive substances in the injured mucosa of rats treated with 50% ethanol. Tea catechin (50, 100 mg/kg twice orally, daily) markedly inhibited the increase in content of thiobarbituric acid-reactive substances in the ulcerated region of acetic acid-induced gastric ulcers on the 7th and 15th days. In addition, at 50, 100 and 200 mg/kg orally, it dose-dependently prevented the decrease in gastric mucosal hexosamine content induced by absolute ethanol, although it failed to inhibit the basal gastric acid secretion. These results suggest that tea catechin may primarily protect gastric mucosa from acute gastric mucosal injury and promote the healing of chronic gastric ulcers by its antioxidant activity and gastric mucus-increasing actions.


Assuntos
Antiulcerosos/uso terapêutico , Camellia sinensis/química , Catequina/uso terapêutico , Úlcera Gástrica/prevenção & controle , Chá/química , Ácido Acético/administração & dosagem , Ácido Acético/toxicidade , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Catequina/administração & dosagem , Catequina/química , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Etanol/toxicidade , Sequestradores de Radicais Livres/antagonistas & inibidores , Sequestradores de Radicais Livres/metabolismo , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Hexosaminas/metabolismo , Imersão/efeitos adversos , Masculino , Estrutura Molecular , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Fitoterapia/métodos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Restrição Física/efeitos adversos , Restrição Física/métodos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Sucralfato/administração & dosagem , Sucralfato/uso terapêutico , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
16.
Biol Pharm Bull ; 28(11): 2080-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16272693

RESUMO

In the present study, we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin, or their combination on renal damage in streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide (LPO) excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after STZ administration. Daily treatment with vitamin E, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals when histopathological evaluation was performed at 4, 8, and 15 weeks (glomerular and mesangial hypertrophy were observed only at 15 weeks). Combined vitamin E and insulin treatment was the most effective at suppressing these renal histopathological changes. These results indicate that combined vitamin E and insulin treatment additively prevents the development and progression of renal damage in diabetic rats. Possible mechanisms for the preventive effect of this combined treatment are discussed.


Assuntos
Antioxidantes/farmacologia , Colesterol na Dieta/toxicidade , Nefropatias Diabéticas/patologia , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Rim/patologia , Vitamina E/farmacologia , Vitaminas/farmacologia , Albuminúria/metabolismo , Animais , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/patologia , Sinergismo Farmacológico , Sequestradores de Radicais Livres/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue
17.
Biol Pharm Bull ; 25(2): 188-92, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11853163

RESUMO

Recently, we reported that low molecular weight (LMW) chitosan (chitosan lactate, average MW: 20,000) prevents the progression of low dose (100 mg/kg, i.p.) streptozotocin-induced slowly progressive diabetes mellitus in male ICR mice. The present study was designed to clarify the effects of LMW chitosan on hyperglycemia, hyperinsulinemia and hypertriglyceridemia in genetically obese diabetic male KK-Ay mice. LMW chitosan (0.05%, 0.2% or 0.8% water solution) was given daily as drinking water to male KK-Ay mice for 11 weeks, from 5 weeks of age. The non-fasting serum glucose levels of control mice continued to increase slowly throughout the experimental period. LMW chitosan lowered the serum glucose levels in a dose-dependent manner. In these diabetic mice, hyperinsulinemia and hypertriglyceridemia were observed, and LMW chitosan was dose-dependently effective in improving both serum biochemical parameters. LMW chitosan at three doses improved overdrinking and polyuria observed in these diabetic mice. It is concluded from these results that LMW chitosan may be useful for the treatment of obesity-related type 2 diabetes mellitus.


Assuntos
Quitina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Quitina/análogos & derivados , Quitosana , Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Peso Molecular , Triglicerídeos/sangue
18.
Biol Pharm Bull ; 27(3): 338-44, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14993799

RESUMO

In the present study we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin or their combination on cataracts of streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after STZ injection. Cataracts were observed from 8 weeks in the control diabetic rats and their incidence of catarats increased to 100% by 12 weeks. The incidence of cataracts in rats treated with vitamin E, insulin and their combination was first seen at 12 weeks and 56%, 20% and 10%, respectively, at 12 weeks and 78%, 50% and 20%, respectively, at 15 weeks. The preventive effects of either agent alone and their combination on the cataracts were in agreement with those obtained by histopathological evaluation of eyeballs. The combined treatment with both agents markedly improved hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These results indicate that the combined treatment with vitamin E and insulin is useful in preventing the development and progression of diabetic cataracts.


Assuntos
Antioxidantes/uso terapêutico , Catarata/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Vitamina E/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Glicemia/efeitos dos fármacos , Peso Corporal , Catarata/etiologia , Catarata/patologia , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Quimioterapia Combinada , Ingestão de Alimentos , Olho/patologia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Peróxidos Lipídicos/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue , Vitamina E/administração & dosagem
19.
Biol Pharm Bull ; 25(8): 1063-71, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12186411

RESUMO

The effects of SK-896, a new human motilin analogue ([Leu13]motilin-Hse), on digestive tract motility in postoperative ileus were evaluated in a dog model of ileus after laparotomy. SK-896 was intravenously administered at 0.17, 0.33 and 0.67 microg/kg starting soon after operation and then at 6-h intervals, for a total of 9 times. SK-896 progressively, dose-dependently and significantly increased the duodenal motility from 1 h after operation. The recovery time of the gastrointestinal-interdigestive migrating complex (GI-IMC) activity, which is an indicator of normal gastrointestinal tract activity after laparotomy, was 56.5 +/- 5.0 h in the control group. SK-896 significantly shortened this recovery time. On the other hand, the plasma SK-896 concentrations declined diexponentially after administration, and can be described by a linear pharmacokinetic model within the dose range used. In addition, the pharmacokinetics of SK-896 did not change significantly at any postoperative time. There was no correlation between the plasma SK-896 concentrations and the intensity of duodenal motility, because the activity in the duodenum decreased transiently 13 h after laparotomy and increased with time thereafter. The changes in the activity are considered to reflect the progressive changes in the state of ileus. In conclusion, SK-896 increased the duodenal motility significantly, shortening the recovery time of GI-IMC-like activity in dogs with post-laparotomy ileus. Therefore, it is expected from these results that SK-896 would be useful and effective for the treatment of gastroparalysis after abdominal surgery.


Assuntos
Modelos Animais de Doenças , Obstrução Intestinal/tratamento farmacológico , Motilina/análogos & derivados , Motilina/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Animais , Cães , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Humanos , Injeções Intravenosas , Obstrução Intestinal/fisiopatologia , Laparotomia/efeitos adversos , Masculino , Motilina/sangue , Motilina/farmacologia , Complicações Pós-Operatórias/fisiopatologia
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