RESUMO
Cyclic nigerosylnigerose (CNN) syrup, containing 76% water-soluble dietary fiber, was prepared from starch on an industrial scale, using isoamylase, 6-α-glucosyltransferase, 3-α-isomaltosyltransferase, and cyclodextrin glucanotransferase. CNN syrup has a unique linkage pattern, consisting mainly of α-1,3 and α-1,6 glucoside linkages, and is characterized by its low weight average molecular weight (807) and moderate sweetness (relative sweetness = 25), unlike in well-known dietary fiber materials. The glass transition temperature of CNN is higher than that of the straight chain structures, maltotetraose and maltosyltrehalose. Even when 40% of normally added sucrose was replaced with CNN syrup, sponge cake puffed up sufficiently. The no observed adverse effect level for a single dose of CNN syrup was 0.88 and 0.89 g dry solid/kg body weight for men and women, respectively. The increase in blood glucose and insulin concentrations during consumption of CNN syrup was lower than that of glucose.
Assuntos
Fibras na Dieta , Glucanos , Feminino , Humanos , Masculino , Amido/química , SacaroseRESUMO
Cyclic nigerosylnigerose (CNN) is a cyclic tetrasaccharide with properties distinct from those of other conventional cyclodextrins. We investigated the relative available energy of CNN in healthy humans. CNN digestibility was determined using brush border membrane vesicles from the small intestines of rats. CNN was not hydrolyzed by rat intestinal enzymes. To investigate breath hydrogen excretion, 13 human subjects were included in a double-blind cross-over, randomized, placebo-controlled study. The effects of CNN on hydrogen excretion were compared with those of a typical nondigestible, fermentable fructooligosaccharide (FOS). In the study participants, hydrogen excretion hardly increased upon CNN and was remarkably lower than for FOS. The available energy value was determined using the fermentability based on breath hydrogen excretion and was evaluated as 0 kcal/g for CNN. CNN was hardly metabolized and hence may be used as a low-energy dietary fiber.
Assuntos
Metabolismo Energético , Glucanos/metabolismo , Adulto , Testes Respiratórios , Método Duplo-Cego , Feminino , Fermentação , Humanos , Hidrogênio/metabolismo , MasculinoRESUMO
We prepared a high-molecular-weight modified dextrin (MWS-1000) from a partial hydrolysate of waxy corn starch with a weight average molecular weight of 1 × 106 (WS-1000) using Paenibacillus alginolyticus PP710 α-glucosyltransferase. The gel permeation chromatography showed that the weight average molecular weight of MWS-1000 was almost the same as that of WS-1000. The side chain lengths of WS-1000 and MWS-1000 after isomaltodextranase digestion were also shown to be similar to each other by high-performance anion exchange chromatography with pulsed amperometric detection. Since MWS-1000 confirmed the presence of α-1,6 bonds by enzyme digestibility, methylation, and 1H-NMR analyses, it was presumed that the structure of MWS-1000 was based on the introduction of α-1,6 glucosyl residues at the nonreducing ends of the partial hydrolysate of waxy corn starch. Furthermore, the MWS-1000 solution was not retrograded even during refrigerated storage or after repeated freeze-thaw cycles.
Assuntos
Dextrinas/síntese química , Glucose/química , Glucosiltransferases/metabolismo , Dextranase/química , Dextrinas/química , Peso Molecular , Espectroscopia de Prótons por Ressonância Magnética , beta-Amilase/químicaRESUMO
High-molecular-weight dextrin (WS-1000) was produced from waxy corn starch and enzymatically modified to link glucose by α-1,6 glycosidic bond at the terminal point of the glucose chain, forming MWS-1000. In this study, the physical properties of MWS-1000 were characterized, and the advantages of its use as a food modifier were described. From rheological and calorimetric studies, it was found that MWS-1000 does not undergo retrogradation, but it does not prevent the retrogradation of WS-1000, suggesting that they have no intermolecular interaction in solution. Investigation of the effect of MWS-1000 on the viscoelasticity of gelatinized wheat starch showed that in the linear viscoelastic region, storage modulus decreased and tan δ increased with increase in replaced MWS-1000 content. In addition, it was confirmed that gelatinized starch containing MWS-1000 showed viscoelastic behavior similar to that of commercially available custard cream.
Assuntos
Dextrinas/biossíntese , Tecnologia de Alimentos , Glucosiltransferases/metabolismo , Elasticidade , Peso Molecular , Amido/química , ViscosidadeRESUMO
A 10-year-old female Papillon dog that had previously developed a mammary tumor was admitted for treatment of a hypoglycemic attack. Blood examination showed severe hypoglycemia and decreased blood insulin concentration. Computed tomography indicated multiple tumors in the cranial and caudal lobes of the right lung. These tumors were resected surgically and diagnosed as pulmonary adenocarcinomas by histopathologic examination. Hypoglycemia was temporarily improved after the resection, but a hypoglycemic event occurred 2 months after the surgery. Immunohistochemistry of the tumor demonstrated the expression of insulin-like growth factor 2 in tumor cells. Western blot analysis revealed the expression of high-molecular-weight (big)-insulin-like growth factor 2 in the tumor region. Insulin-like growth factor 2 mRNA expression was also confirmed in the tumor using reverse transcription-polymerase chain reaction. These findings indicate the diagnosis of non-islet cell tumor-induced hypoglycemia caused by big-insulin-like growth factor 2 produced by the tumor in the dog. This report provides information on differentiating tumors that cause paraneoplastic hypoglycemia.
Assuntos
Adenocarcinoma/veterinária , Doenças do Cão , Hipoglicemia/veterinária , Fator de Crescimento Insulin-Like II/metabolismo , Neoplasias Mamárias Animais , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Animais , Cães , Feminino , Hipoglicemia/etiologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/veterinária , Neoplasias Mamárias Animais/complicações , Neoplasias Mamárias Animais/metabolismoRESUMO
This study aimed to investigate the expression of receptor-type tumour endothelial marker 8 (TEM8RT) in canine mammary gland carcinomas (CMGCs) using immunohistochemistry and to evaluate the association between carcinoma cell TEM8RT expression and tumour histological features, histological grades and the differentiation status of neoplastic epithelial cells. TEM8RT expression was more frequently detected in simple carcinomas (tubular and tubulopapillary) than in solid carcinomas, and it was significantly correlated with histological grade â tumours and a low mitotic index. Additionally, TEM8RT+ carcinoma cells were more frequently found in CMGCs showing luminal progenitor-like phenotypes, such as Notch1+, CK19+/CK5+/CD49f+ and CK19+/CK5-/CD49f+. Double-labelling immunofluorescence detection techniques confirmed that most TEM8RT+ carcinoma cells expressed CD49f, Notch1 and CK19. However, TEM8RT immunoreactivity was not found in carcinoma cells expressing GATA3, which upregulates mature luminal cell differentiation. Furthermore, TEM8RT+ carcinoma cells were detected in a few CMGCs showing basal/stem cell-like phenotypes such as CK19-/CK5+/CD49f+ and CK19-/CK5+/CD49f-. These findings indicate that TEM8RT is expressed in luminal progenitor-like carcinoma cells in CMGCs. Since TEM8 enhances self-renewal in human mammary stem/progenitor cells, it also may be involved in maintenance of luminal progenitor-like carcinoma cells, resulting in prevention of their transition to basal/stem cell-like carcinoma cells and development of less malignant CMGCs. Therefore, TEM8RT may be useful for indicating prognostic outcomes and identifying the possible ontogeny of carcinoma cells in mammary gland tumours.
Assuntos
Carcinoma , Doenças do Cão , Glândulas Mamárias Humanas , Neoplasias Mamárias Animais , Animais , Cães , Humanos , Integrina alfa6 , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Carcinoma/veterinária , Carcinoma/patologia , Moléculas de Adesão Celular , Fenótipo , Neoplasias Mamárias Animais/patologia , Doenças do Cão/patologiaRESUMO
This study aimed to investigate the expression of type VI collagen α3 chain (COL6a3) in neoplastic cells of canine mammary gland carcinomas (CMGCs) using immunohistochemistry (IHC) and to evaluate the association between COL6a3 expression and tumor histological features, histological grades, and the differentiation status of neoplastic epithelial cells. COL6a3 expression in carcinoma cells was significantly associated with histologically low malignancy and low mitotic indices. In addition, COL6a3+ carcinoma cells were more frequently detected in simple carcinomas (tubular and tubulopapillary types) than in solid carcinomas. These findings indicate that reduced expression of COL6a3 in carcinoma cells contributes to the malignant phenotype in CMGCs. We also showed that COL6a3 expression in the carcinoma cells was more frequently detected in CK19+/CD49f + and/or CK19+/CK5+ tumors. In addition, COL6a3+/CK19+/CD49f + and COL6a3+/CK19+/CK5+ tumors consisted of CK19+/CD49f + and CK19+/CD49f- cells, and CK19+/CK5+ and CK19+/CK5- cells, respectively. Most of these tumors more frequently expressed GATA3, but not Notch1. These results indicate that COL6a3 is expressed in CMGCs containing both luminal progenitor-like and mature luminal-like cells and showing differentiation ability into mature luminal cells. It is possible that COL6 may be involved in the differentiation of luminal progenitor-like carcinoma cells into mature luminal-like carcinoma cells in CMGCs, which may suppresses the development of malignant phenotypes in CMGCs.
Assuntos
Carcinoma , Doenças do Cão , Animais , Cães , Colágeno Tipo VI/genética , Integrina alfa6/genética , Carcinoma/patologia , Carcinoma/veterinária , Diferenciação Celular , Fenótipo , Doenças do Cão/metabolismoRESUMO
Fructooligosaccharides (FOS) are a prebiotic supplement, which can enhance immunological responses in the host to activate mucosal immunity probably through regulation of gastrointestinal microflora. Nonetheless, the therapeutic potential of prebiotics on allergic pathologies has not been fully elucidated. Therefore, the purpose of this study was to evaluate the preventive and therapeutic effects of dietary supplementation with FOS on a murine model of allergic peritonitis induced by ovalbumin (OVA). Male C3H/HeN mice were intraperitoneally administrated with OVA (1 µg) bi-weekly (Day 0-42, total four times) and were fed a diet containing 0 or 2.5% FOS ad libitum (Day 7-43). At Day 43, mice were killed and several parameters were evaluated. As results, supplementation with FOS alleviated OVA-related peritoneal inflammation characterized by trafficking of polymorphonuclear leukocytes such as eosinophils and neutrophils in the peritoneal cavity. Also, FOS significantly suppressed the protein level of interleukin (IL)-5 and eotaxin in the peritoneal lavage fluid elicited by OVA. In addition, a FOS-supplemented diet significantly reduced the serum allergen specific-IgG(1) level, whereas it significantly increased total IgA levels in the cecal contents as compared with a control diet in the presence of OVA. These results suggest that dietary supplementation with FOS can prevent/ameliorate allergic peritoneal inflammation induced by OVA. The efficacy can at least partially be associated with the regulation of Ig class switching and inhibition of the local expression of IL-5 and eotaxin.
Assuntos
Suplementos Nutricionais , Hipersensibilidade/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Peritonite/tratamento farmacológico , Animais , Hipersensibilidade/imunologia , Imunoglobulina A/imunologia , Intestino Delgado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Lavagem Peritoneal , Peritonite/imunologiaRESUMO
CASE SUMMARY: A 4-year-old castrated male domestic shorthair cat with a continuous cough was brought to a private veterinary clinic for detailed examination. Radiography of the thoracic cavity revealed a severe radiopaque region in the caudal lobe of the right lung. At 108 days after the initial visit, CT showed a mass of 27 × 23 × 18 mm in the caudal lobe of the right lung. At that time, no abnormalities in other organs except for the lung were detected on CT and peripheral blood and blood biochemistry tests. The mass in the caudal lobe of the right lung was resected by lobectomy; it had a white surface and was firm. Histopathologically, the mass was non-encapsulated, showing an unclear boundary with surrounding tissues. The mass comprised large, round or polygonal neoplastic cells arranged in a diffuse pattern. Immunohistochemically, neoplastic cells were diffusely positive for CD20, feline leukaemia virus (FeLV) p27 and FeLV glycoprotein 70 but negative for CD3, CD204 and E-cadherin. Based on these findings, diffuse large B-cell lymphoma associated with FeLV infection was diagnosed. Although the cat showed no clinical signs of gastrointestinal or respiratory injury, a routine ultrasonography revealed thickening in the jejunum wall 196 days after lobectomy, and subsequent fine-needle aspiration examination confirmed high-grade lymphoma. RELEVANCE AND NOVEL INFORMATION: This is the first report of primary pulmonary diffuse large B-cell lymphoma associated with FeLV infection in a young cat.
RESUMO
Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4+ cells were stimulated with IL2, antiCD3 and antiCD28 antibodies for 3 days, followed by further stimulation with IL2 for 7 days. Subsequently, cells were stimulated with IL2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 µg/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 µM gHesp. Following culture for 28 days, reverse transcriptionquantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase7 (MMP7), nicotinamide nucleotide transhydrogenase (NNT) and CXC motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotileexposure induced alterations in MMP7, NNT and IL17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposureinduced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with highrisk human populations exposed to asbestos, such as workers involved in asbestoshandling activities.
Assuntos
Amianto/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Suplementos Nutricionais , Hesperidina/farmacologia , Mesotelioma Maligno/imunologia , Trealose/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Humanos , Interferon gama/imunologia , Interleucina-17/imunologia , Masculino , Mesotelioma Maligno/induzido quimicamente , Mesotelioma Maligno/prevenção & controle , Pessoa de Meia-Idade , Receptores CXCR3/imunologiaRESUMO
Cocoa powder is rich in polyphenols, such as catechins and oligomeric procyanidins, and has a hypocholesterolemic effect in humans. This study evaluated the principal active components and potential mechanism(s) for the hypocholesterolemic effect of polyphenolic substances from cocoa powder in rats. Male Wistar rats were fed a 1% high-cholesterol diet (HC) or a high-cholesterol diet containing 1% polyphenol extract from cocoa powder (PE) or a mixture of 0.024% catechin and 0.058% epicatechin (CE) for 4 weeks. We also examined the effects of these polyphenolic substances on micellar cholesterol solubility in vitro. The PE group had significantly lower plasma cholesterol concentrations, and had significantly greater fecal cholesterol and total bile acids excretion than the HC group. The CE group diet did not influence plasma cholesterol concentrations, or fecal cholesterol or total bile acids excretion. Micellar solubility of cholesterol in vitro was significantly lower for procyanidin B2 (dimer), B5 (dimer), C1 (trimer) and A2 (tetramer), which are the main components of polyphenol extract from cocoa powder, compared to catechin and epicatechin. These results suggest that oligomeric procyanidins from cocoa powder are the principal active components responsible for the hypocholesterolemic effect, and inhibit the intestinal absorption of cholesterol and bile acids through the decrease in micellar cholesterol solubility.
Assuntos
Cacau/química , Proantocianidinas/farmacologia , Animais , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Fezes/química , Lipídeos/sangue , Masculino , Ratos , Ratos Wistar , Esteroides/metabolismo , Esterol O-Aciltransferase/metabolismoRESUMO
Previously, we identified four metabolites of (-)-epicatechin in blood and urine: (-)-epicatechin-3'-O-glucuronide (E3'G), 4'-O-methyl-(-)-epicatechin-3'-O-glucuronide (4'ME3'G), (-)-epicatechin-7-O-glucuronide (E7G), and 3'-O-methyl-(-)-epicatechin-7-O-glucuronide (3'ME7G) (Natsume et al. Free Radical Biol. Med. 34, 840-849, 2003). The aim of the current study was to compare the antioxidative activities of these metabolites with that of their parent compound. After oral administration of (-)-epicatechin, E3'G and 4'ME3'G were isolated from human urine, and E7G and 3'ME7G isolated from rat urine. We found that these compounds inhibited peroxynitrite-mediated tyrosine nitration, in the following order of potency: E3'G > (-)-epicatechin > E7G = 3'ME7G. = 4'ME3'G. These results demonstrate that the metabolites of (-)-epicatechin retain antioxidative activity on peroxynitrite-induced oxidative damages to some extent.
RESUMO
BACKGROUND: Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis. OBJECTIVE: We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects. DESIGN: Twenty-five subjects were randomly assigned to ingest either 12 g sugar/d (control group) or 26 g cocoa powder and 12 g sugar/d (cocoa group) for 12 wk. Blood samples were collected before the study and 12 wk after intake of the test drinks. Plasma lipids, LDL oxidative susceptibility, and urinary oxidative stress markers were measured. RESULTS: At 12 wk, we measured a 9% prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group. This prolongation in the cocoa group was significantly greater than the reduction measured in the control group (-13%). A significantly greater increase in plasma HDL cholesterol (24%) was observed in the cocoa group than in the control group (5%). A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL. At 12 wk, there was a 24% reduction in dityrosine from baseline concentrations in the cocoa group. This reduction in the cocoa group was significantly greater than the reduction in the control group (-1%). CONCLUSION: It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol.
Assuntos
Cacau , HDL-Colesterol/sangue , Carboidratos da Dieta , Suplementos Nutricionais , Flavonoides/uso terapêutico , Lipoproteínas LDL/sangue , Fenóis/uso terapêutico , Bebidas , Biomarcadores/urina , Índice de Massa Corporal , Catequina/urina , Registros de Dieta , Gorduras na Dieta , Humanos , Lipoproteínas/sangue , Masculino , Oxirredução , Estresse Oxidativo , Polifenóis , SacaroseRESUMO
In epidemiological studies, exposure to ambient particulate matter (PM) has been reported to be positively associated with mortality in subjects with diabetes mellitus. Diesel exhaust particles (DEP) are major constituents of atmospheric PM. However, there is no experimental evidence for the relation of DEP to diabetes mellitus and its complications. We investigated the effects of DEP inoculated intratracheally on diabetic changes and nonalcoholic fatty liver disease (NAFLD) in diabetic obese and control mice. db/db mice and the corresponding nondiabetic db/+m mice received exposure to vehicle or DEP every two weeks. Animals were examined with biochemistry, histology, and immunohistochemistry for hexanoyl-lysine (HEL) in the liver. In the db/+m mice, pulmonary exposure to DEP did not increase levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) compared to that to vehicle. In the db/db mice, however, the exposure to DEP increased the levels of AST and ALT compared to that to vehicle. Only in the db/db mice, DEP enhanced the magnitude of steatosis and formation of HEL, a marker of oxidative stress, in the liver compared to vehicle. These results suggest that pulmonary exposure to DEP, PM, enhances steatosis in the liver of obese diabetic subjects possibly via enhanced oxidative stress.
Assuntos
Colesterol/sangue , Pulmão/efeitos dos fármacos , Triglicerídeos/sangue , Emissões de Veículos/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Feminino , Lipídeos/análise , Fígado/efeitos dos fármacos , Fígado/patologia , Lisina/análogos & derivados , Lisina/síntese química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Estresse OxidativoRESUMO
OBJECTIVE: Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. METHODS: C57BL/KsJ-db/db (db/db) diabetic obese mice and C57BL/KsJ-db/+m (db/+m) control mice were fed a diet containing 0% w/w CLPr (0% CLPr), 0.5% w/w CLPr (0.5% CLPr), or 1.0% w/w CLPr (1.0% CLPr) from age 3 wk to age 6 wk. Levels of blood glucose were measured at 4 and 5 wk of age. The animals were sacrificed and the levels of blood glucose and fructosamine were measured at 6 wk of age. RESULTS: The levels of blood glucose and fructosamine were higher in the db/db mice than in the db/+m mice fed a diet containing 0%, 0.5%, or 1.0% CLPr. In the db/+m mice, the levels of blood glucose or fructosamine were not significantly different across animals fed 0% CLPr, 0.5% CLPr, and 1.0% CLPr. In the db/db mice, however, a diet containing 0.5% or 1.0% CLPr decreased the levels of blood glucose and fructosamine compared with that containing 0% CLPr without significant effects on body weights or food consumption. CONCLUSION: Dietary supplementation with CLPr can dose-dependently prevent the development of hyperglycemia in diabetic obese mice. The dietary intake of food or drinks produced from cacao beans might be beneficial in preventing the onset of type 2 diabetes mellitus.
Assuntos
Glicemia/efeitos dos fármacos , Cacau , Hiperglicemia/prevenção & controle , Hipoglicemiantes/farmacologia , Proantocianidinas/farmacologia , Envelhecimento/fisiologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Cacau/química , Diabetes Mellitus Experimental/prevenção & controle , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Frutosamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Período Pós-PrandialRESUMO
Two experiments were performed to examine the effects of fructooligosaccharides (FOS) on the development of obesity. In the first experiment, Wistar rats were orally administered a 2.5 g/kg body weight lipid emulsion containing FOS, and the subsequent elevation of plasma triglycerides was significantly suppressed compared with that in rats receiving lipid emulsion alone. In the second experiment, C57BL/6J male mice were fed a high-fat "western" diet with or without 2.5% FOS supplementation (n = 10/group) ad libitum for 12 weeks. Body weight and percent body fat were lower in mice fed FOS than in controls. Furthermore, the weight of the visceral adipose tissue, and the weight and triglyceride content of the liver were significantly lower in the high-fat + FOS group. Fecal excretion of lipids was markedly enhanced by FOS consumption. These results indicate that dietary FOS suppress high-fat diet-induced body fat accumulation, and inhibit intestinal absorption of dietary fat.
Assuntos
Ingestão de Energia/efeitos dos fármacos , Obesidade/dietoterapia , Oligossacarídeos/administração & dosagem , Triglicerídeos/sangue , Tecido Adiposo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Humanos , Camundongos , Obesidade/sangue , Obesidade/patologia , Ratos , Ratos WistarRESUMO
The protective activity of rosmarinic acid from Perilla frutescens on liver injury induced by LPS in D-GalN-sensitized mice was examined. We also investigated the effects of antitumor necrosis factor-alpha antibody (anti-TNF), superoxide dismutase (SOD), and aminoguanidine (AG) on this model in order to elucidate the mechanism of rosmarinic acid protection. Perilla extract (PE) and rosmarinic acid (RA) treatments significantly reduced the elevation of plasma asparatate aminotransferase levels, as well as anti-TNF and SOD treatment, compared with controls, but this reduction was not seen in the AG group. These results were confirmed by histological examination using hematoxylin-eosin and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Increases in tumor necrosis factor-alpha (TNF-alpha) mRNA expression in liver and in plasma TNF-alpha levels, which were observed in control mice, were not significantly reduced by PE or RA. PE and RA treatments also did not significantly diminish iNOS mRNA expression or plasma nitrate/nitrite levels. Nitrotyrosine and N(epsilon)-(hexanonyl)lysine (HEL) production, the residue of oxidative stress, was observed in livers from controls, but not in those mice pretreated with PE or RA. These results suggest that the liver protection of RA is due to the scavenging or reducing activities-superoxide or peroxynitirite rather than to inhibition of TNF-alpha production.
Assuntos
Cinamatos/farmacologia , Galactosamina/farmacologia , Lipopolissacarídeos/farmacologia , Perilla frutescens/metabolismo , Alanina Transaminase/metabolismo , Animais , Depsídeos , Imuno-Histoquímica , Fígado/lesões , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Modelos Químicos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Estresse Oxidativo , Inibidores da Agregação Plaquetária/farmacologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , Ácido RosmarínicoRESUMO
Recently we identified four conjugated glucuronide metabolites of epicatechin, (-)-epicatechin-3'-O-glucuronide (E3'G), 4'-O-methyl-(-)-epicatechin-3'-O-glucuronide (4'ME3'G), (-)-epicatechin-7-O-glucuronide (E7G) and 3'-O-methyl-(-)-epicatechin-7-O-glucuronide (3'ME7G) from plasma and urine. E3'G and 4'ME3'G were isolated from human urine, while E7G and 3'ME7G were isolated from rats that had received oral administration of (-)-epicatechin (Natsume et al. (2003), Free Radic. Biol. Med. 34,840-849). It has been suggested that these metabolites possess considerable in vivo activity, and therefore we carried out a study to compare the antioxidant activities of the metabolites with that of the parent compound. This was achieved by measuring superoxide scavenging activity, reduction of plasma TBARS production and reduced susceptibility of low-density-lipoprotein (LDL) to oxidation. (-)-Epicatechin was found to have more potent antioxidant activity than the conjugated glucuronide metabolites. Both (-)-epicatechin and E7G had marked antioxidative properties with respect to superoxide radical scavenging activity, plasma oxidation induced by 2,2'-azobis-(2-aminopropane) dihydrochloride (AAPH) and LDL oxidation induced by copper ions or 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). In contrast, the other metabolites had light antioxidative activities over the range of physiological concentrations found in plasma.
Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Catequina/sangue , Catequina/farmacologia , Glucuronatos/sangue , Glucuronatos/farmacologia , Animais , Antioxidantes/química , Compostos Azo/antagonistas & inibidores , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Glucuronatos/química , Humanos , Lipoproteínas LDL/química , Estrutura Molecular , Nitrilas/antagonistas & inibidores , Oxidantes/antagonistas & inibidores , Oxirredução/efeitos dos fármacos , Ratos , Superóxidos/química , Substâncias Reativas com Ácido Tiobarbitúrico/químicaRESUMO
Proanthocyanidins derived from cacao (CLP) have various antipathophysiological functions. We have tested whether dietary supplementation with CLP prevents cataract formation in rats with diabetes induced by streptozotocin (STZ), using histological, histochemical, and biochemical analyses. Starting at 7 days after the streptozotocin challenge, the animals were fed either a normal diet or a diet containing 0.5% w/w CLP over 10 weeks. There were no significant differences in plasma and urine glucose concentrations, plasma fructose amines, and plasma thiobarbituric reactive substances (TBARS) between the two dietary groups. Antioxidant status as assessed by measuring lipid peroxide production in plasma in response to azocompounds was lower in the STZ-rats fed control diet than in animals fed CLP. Opacity was first detected in the lenses of the control dietary group 5 weeks after STZ injection and cataracts had developed in the majority of these animals by 10 weeks. These changes were rarely seen in the STZ/CLP diet group. Histological examinations of the eyes of the STZ-treated normal diet group revealed focal hyperplasia of the lens epithelium and liquefaction of cortical fibers. There were similar but considerably less severe changes in the animals fed CLP. Hydroxynonenal (HNE), a marker of oxidative stress, was detected immunohistochemically in the lenses of the STZ-treated normal diet group, but not of those receiving CLP. Our findings suggest that CLP inhibits diabetes-induced cataract formation possibly by virtue of its antioxidative activity.