RESUMO
We experienced the case of a patient with advanced breast cancer who failed to receive comprehensive care despite regular video conferencing with her physician during the COVID-19 pandemic, resulting in delayed detection of liver metastasis. Inter-hospital collaboration is required to provide uninterrupted cancer care to those disproportionately affected by crises.
RESUMO
Pioglitazone is one of the thiazolidinediones (TZDs) and an insulin-sensitive drug for type 2 diabetes. In our previous study, a combination of pioglitazone and fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) was shown to inhibit pioglitazone-induced side effects, such as accumulation of subcutaneous fat and body weight gain. However, the effects of the discontinuation of fish oil after combination treatment with TZD and fish oil are not clear. In this study, discontinuation of fish oil for 4 weeks showed several unfavorable effects: (1) return of plasma adiponectin level, (2) reversal of the inhibition of lipogenesis and activation of fatty acid ß-oxidation in liver, (3) increase in hypertrophic adipocytes in epidydimal white adipose tissue (WAT) and (4) accumulation of lipids in brown adipose tissue (BAT). However, insulin resistance was ameliorated by pioglitazone with or without fish oil treatment and the discontinuation of fish oil. These findings indicate that discontinuation of n-3 PUFA after combination therapy with TZDs adversely affects lipid metabolism and energy homeostasis in liver, epididymal WAT and BAT.
Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Óleos de Peixe/administração & dosagem , Resistência à Insulina , Pioglitazona/administração & dosagem , Adiponectina/sangue , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal , Diferenciação Celular , Homeostase , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Oxigênio/metabolismoRESUMO
The elderly patients with type 2 diabetes suffer more adverse drug events than young adults due to pharmacokinetic and pharmacodynamic changes associated with aging. Reducing the risks of these medication-related problems are equally important for the clinical care of older type 2 diabetes patients. Pioglitazone is used for treating type 2 diabetes as an oral antidiabetic drug. Despite pioglitazone is used helpful insulin sensitizers, the accumulation of subcutaneous fat is considered a major adverse effect of pioglitazone therapy. We investigated to reduce the adverse effect of pioglitazone by combination with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in aged diabetic KK mice. The accumulation of subcutaneous fat associated with high-dose pioglitazone is reduced by fish oil, suppressing lipogenesis and stimulating fatty acid ß-oxidation in the liver. Our data suggest that adding fish oil to low-dose pioglitazone results in antidiabetic efficacy similar to that of the high-dose without concomitant body weight gain.
Assuntos
Envelhecimento/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Óleos de Peixe/administração & dosagem , Hipoglicemiantes/administração & dosagem , Pioglitazona/administração & dosagem , Envelhecimento/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/análise , Quimioterapia Combinada , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/análise , Ácidos Graxos/metabolismo , Óleos de Peixe/análise , Humanos , Insulina/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , CamundongosRESUMO
Chondroitin sulfate (CS) is a sulfated polysaccharide produced by chondrocytes. Alkaline phosphatase (ALP) is an important enzyme involved in the mineralization of chondrocytes. In recent years, it has been reported that CS regulates the differentiation of various cells. In this study, we investigated the effect of supplemented CS on ALP activity and mineralization of the chondrogenic cell line, ATDC5. In addition, hyaluronic acid (HA), a non-sulfated and acidic polysaccharide, was used in comparison to CS. CS and HA significantly suppressed ALP activity without affecting ATDC5 cell proliferation. In addition, although the inhibition of ALP activity was observed at every time point, Alp mRNA expression level was not affected by CS. The suppressive effect of CS on ALP activity was abrogated by pre-treatment with chondroitinase ABC (CSase). CS and L-homoarginine (hArg), an inhibitor of ALP, significantly suppressed mineralization in ATDC5 cells. In conclusion, supplemented CS directly inhibits ALP to prevent the progression of chondrocytes from differentiation to mineralization.
Assuntos
Fosfatase Alcalina/antagonistas & inibidores , Calcificação Fisiológica/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Sulfatos de Condroitina/farmacologia , Ácido Hialurônico/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Condrócitos/fisiologia , Condrogênese/efeitos dos fármacos , Condroitina ABC Liase/metabolismo , Sulfatos de Condroitina/metabolismo , Homoarginina/farmacologia , Camundongos , RNA MensageiroRESUMO
The effect of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) on bone metabolism in ovariectomized (OVX) mice was studied. After 12 weeks of feeding with 0.2% GlcN and 0.2% GlcNAc, the femoral bone mineral density in OVX mice was significantly increased compared with that in OVX mice fed the control diet. Histomorphometric analysis of the tibia indicated that the rates of osteogenesis and bone resorption were reduced due to the GlcN diet. The erosion depth of osteoclasts on the tibia in GlcN- and GlcNAc-fed OVX mice was significantly lower than that in the control OVX mice. The number of tartrate-resistant acid phosphatase-positive osteoclasts induced from bone marrow stem cells isolated from GlcN-fed OVX mice was significantly lower than that from control OVX mice. A loss of uterine weight and higher serum calcium concentration in the GlcN- and GlcNAc-fed OVX mice were observed. The results suggest that the intake of GlcN suppresses bone loss by inhibiting osteoclast differentiation and activity in a nonestrogenic manner.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Glucosamina/uso terapêutico , Osteoclastos/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Células da Medula Óssea/citologia , Reabsorção Óssea/sangue , Reabsorção Óssea/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/sangue , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Glucosamina/farmacologia , Magnésio/sangue , Menopausa , Camundongos , Osteoclastos/citologia , Ovariectomia , Fósforo/sangueRESUMO
BACKGROUND: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear. PURPOSE: To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts. STUDY DESIGN: Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures. METHODS: Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot. RESULTS: Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways. CONCLUSION: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.
Assuntos
Benzoxepinas/farmacologia , Citrus/química , Limoninas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Fosfatase Ácida/metabolismo , Animais , Reabsorção Óssea , Diferenciação Celular/efeitos dos fármacos , Isoenzimas/metabolismo , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Células RAW 264.7/efeitos dos fármacos , Fosfatase Ácida Resistente a TartaratoRESUMO
Accumulation of advanced glycation end products (AGEs) leads to various diseases such as diabetic complications and arteriosclerosis. In this study, we examined the effect of pomegranate fruit extract (PFE) and its constituent polyphenols on AGE formation in vivo and in vitro. PFE, fed with a high-fat and high-sucrose (HFS) diet to KK-A(y) mice, significantly reduced glycation products such as glycoalbumin (22.0 ± 2.4%), hemoglobin A1c (5.84 ± 0.23%), and serum AGEs (8.22 ± 0.17 µg/mL), as compared to a control HFS group (30.6 ± 2.6%, 7.45 ± 0.12%, and 9.55 ± 0.17 µg/mL, respectively, P < 0.05). In antiglycation assays, PFE, punicalin, punicalagin, ellagic acid, and gallic acid suppressed the formation of AGEs from bovine serum albumin and sugars. In this study, we discuss the mechanism of the antiglycation effects of PFE and its components in vivo and in vitro.
Assuntos
Frutas/química , Glicosilação/efeitos dos fármacos , Lythraceae/química , Extratos Vegetais/química , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Produtos Finais de Glicação Avançada/química , Produtos Finais de Glicação Avançada/metabolismo , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Polifenóis/químicaRESUMO
Oral supplementation with collagen hydrolysate (CH) has been shown to improve the condition of the skin in humans and experimental animals. Several hydroxyproline-containing oligo-peptides were previously detected in human peripheral blood after the ingestion of CH, and the two dipeptides, prolyl-hydroxyproline (PO) and hydroxyprolyl-glycine (OG), have been proposed to have beneficial effects on human health. When HR-1 hairless mice were fed a HR-AD diet, which lacked magnesium and zinc, transepidermal water loss (TEWL) increased and water content of stratum corneum decreased. In the present study, we investigated the effects of dietary PO and OG on skin barrier dysfunction in HR-1 hairless mice. Mice were fed a HR-AD diet with or without PO (0.15%) and OG (0.15%) for 35 consecutive days. The administration of PO and OG significantly decreased TEWL, and significantly increased water content of stratum corneum. A DNA microarray analysis of the dorsal skin revealed differences in gene expression between the group administered PO and OG and the control group. We also identified muscle-related Gene Ontology as a result of analyzing the up-regulated genes. These results suggested that the administration of PO and OG improved skin barrier dysfunction and altered muscle-related gene expression.
Assuntos
Colágeno/administração & dosagem , Dipeptídeos/administração & dosagem , Epiderme/efeitos dos fármacos , Perda Insensível de Água/efeitos dos fármacos , Administração Oral , Animais , Colágeno/química , Dieta , Dipeptídeos/química , Epiderme/metabolismo , Epiderme/patologia , Humanos , Hidrólise , Masculino , Camundongos , Camundongos Pelados , Músculo Estriado/efeitos dos fármacos , Músculo Estriado/metabolismo , Transcriptoma/efeitos dos fármacosRESUMO
Long-chain N-vanillyl-acylamides (LCNVAs) were generated from plant oils and vanillylamine (VA) by nucleophilic amidation without any catalytic reagents. The resulting LCNVAs varied according to the fatty acid composition of the plant oil used. Therefore, the LCNVAs contained in Capsicum oleoresins were products that were spontaneously generated from the oleoresin during storage.
Assuntos
Amidas/química , Óleos de Plantas/química , Óleo de Soja/química , Benzilaminas/química , Capsaicina/análogos & derivados , Capsaicina/química , Azeite de Oliva , Trioleína/químicaRESUMO
BACKGROUND: Salacia reticulata (SR) is a plant native to Sri Lanka. In ayurvedic medicine, SR bark preparations, taken orally, are considered effective in the treatment of rheumatism and diabetes. We investigated the ability of SR leaves (SRL) to inhibit in vitro the interleukin-1ß (IL-1ß)-activated proliferation of synoviocyte-like cells derived from rheumatoid arthritis model mice. FINDINGS: Inflammatory synovial tissues were harvested from type II collagen antibody-induced arthritic mice. From these tissues, a synoviocyte-like cell line was established and named MTS-C H7. To determine whether SRL can suppress cell proliferation and gene expression in MTS-C H7 cells, fractionation of the SRL hot-water extract was performed by high-performance liquid chromatography (HPLC), liquid-liquid extraction, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and protease digestion.The 50% inhibitory concentration of the SRL hot-water extract against MTS-C H7 cells proliferation was ~850 µg/mL. Treatment with a low dose (25 µg dry matter per millilitre) of the extract inhibited IL-1ß-induced cell proliferation and suppressed the expression of the matrix metalloproteinase (MMP) genes in MTS-C H7 cells. Various polyphenolic fractions obtained from HPLC and the fractions from liquid-liquid extraction did not affect cell proliferation. Only the residual water sample from liquid-liquid extraction significantly affected cell proliferation and the expression of MMP genes. The results of SDS-PAGE and protease digestion experiment showed that low molecular weight proteins present in SRL inhibited the IL-1ß-activated cell proliferation. CONCLUSIONS: We surmised that the residual water fraction of the SRL extract was involved in the inhibition of IL-1ß-activated cell proliferation and regulation of mRNA expression in MTS-C H7 cells. In addition, we believe that the active ingredients in the extract are low molecular weight proteins.
Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/patologia , Proliferação de Células/efeitos dos fármacos , Temperatura Alta , Interleucina-1beta/metabolismo , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Salacia , Membrana Sinovial/efeitos dos fármacos , Água/química , Animais , Antirreumáticos/química , Antirreumáticos/isolamento & purificação , Artrite Experimental/genética , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Regulação para Baixo , Eletroforese em Gel de Poliacrilamida , Concentração Inibidora 50 , Extração Líquido-Líquido , Metaloproteinases da Matriz/genética , Camundongos , Camundongos Endogâmicos DBA , Peso Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Plantas Medicinais , RNA Mensageiro/metabolismo , Salacia/química , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologiaRESUMO
Salacia reticulata is a native plant of Sri Lanka. In the traditional medicine of Sri Lanka and India, Salacia reticulata bark is considered orally effective in the treatment of rheumatism, gonorrhea, skin disease and diabetes. We have investigated, both in vivo and in vitro, whether the leaf of Salacia reticulata (SRL) can ameliorate collagen antibody-induced arthritis (CAIA) in mice as the rheumatoid arthritis (RA) model. The mice were fed a lard containing chow diet (AIN-93G) or the same diet containing 1% (w/w) SRL powder. All mice were bred for 23 days. On day 7 or 14 after LPS injection, mice were killed, and tissue and blood samples were collected. Histological analysis was performed, and serum levels of inflammatory mediators and the mRNA levels of inflammation-related genes and osteoclast-related genes were measured. SRL treatment ameliorated the rapid initial paw swelling, inflammatory cells infiltration, skeletal tissues damage, osteoclast activation and the mRNA levels for osteoclast-related genes compared with the CAIA mice. However, the serum and mRNA levels of inflammatory mediators did not differ between the CAIA mice and the SRL-treated mice. SRL might reduce the inflammatory cells induction and skeletal tissue degradation by CAIA by the regulating osteoclastogenesis.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Kothala himbutu (Salacia reticulata) is a medicinal plant that has been used in Ayurvedic system of Indian and Sri Lankan traditional medicine to treat diabetes. AIM OF THE STUDY: This study aimed to clarify the mechanism(s) by which aqueous extracts of Kothala himbutu (KTE) stems decreases fasting blood glucose levels. MATERIALS AND METHODS: Gene expression profiles were assessed by DNA microarray and RT-PCR analyses of RNA from the liver of KK-Ay diabetic mice administered KTE or control distilled water for 4 weeks, and from cultured liver cells treated with freeze-dried KTE (KTED) or selected phenolic compounds. RESULTS: DNA microarray and RT-PCR analyses revealed that gluconeogenic fructose-1,6-bisphosphatase (FBP) was decreased compared with the control in KTE-treated KK-Ay mice. RT-PCR analysis using cultured liver cells treated with KTED and/or actinomycin D or cycloheximide, revealed that KTED directly decreased FBP mRNA levels via destabilization of the mRNA. One compound in KTE, mangiferin, was demonstrated to dose-dependently down-regulate FBP mRNA. CONCLUSIONS: These findings suggest that the mangiferin in KTE acts directly on liver cells and down-regulates the gluconeogenic pathway through regulation of FBP expression, thereby decreasing fasting blood glucose levels in mice. Our results demonstrate that gluconeogenic gene regulation is one possible mechanism by which KT exerts its effects in traditional diabetic medicine.
Assuntos
Glicemia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Salacia/química , Xantonas/farmacologia , Animais , Linhagem Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Relação Dose-Resposta a Droga , Frutose-Bifosfatase/efeitos dos fármacos , Frutose-Bifosfatase/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ayurveda , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Extratos Vegetais/administração & dosagem , Caules de Planta , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sri Lanka , Xantonas/administração & dosagem , Xantonas/isolamento & purificaçãoRESUMO
Kothala himbutu is a traditional Ayurvedic medicinal plant used to treat diabetes. We aimed to evaluate the safety of an aqueous extract of Kothala himbutu stem (KTE) in normal mice. The mice were divided into two groups: one was administered KTE and the other distilled water for 3 weeks. During the test period, the groups showed no significant differences in body weight gain or plasma parameters, such as fasting blood glucose level, oral glucose tolerance test, or aspartate transaminase (AST) or alanine transaminase (ALT) activity. DNA microarray analysis revealed that expression of genes of known function, such as those for the stress response, ribosomal proteins, transcription, cell function, the inflammatory/immune response, and metabolism (xenobiotic, glutathione, etc.) remained largely unaffected by KTE. However some genes such as catechol-o-methyltransferase and succinyl-CoA synthetase were regulated by KTE, indicating that KTE is not toxic to normal mice and might be effective as a functional food.
Assuntos
Fígado/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Extratos Vegetais/farmacologia , Caules de Planta/química , Segurança , Salacia/química , Água/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Jejum , Perfilação da Expressão Gênica , Teste de Tolerância a Glucose , Saúde , Fígado/anatomia & histologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Período Pós-Prandial/efeitos dos fármacosRESUMO
We have previously reported that rats fed on a vitamin B12 (B12)-deficient diet containing 180 g soybean protein per kg diet showed marked histologic damage in their testes. In this paper, we report the effect of B12-deficiency on B12-dependent methionine synthase in the rats' testes and the effect of methionine supplementation of the diet on testicular damage. Rats were fed the soybean protein-based B12-deficient diet for 120 d. We confirmed that those rats were in serious B12-deficiency by measuring urinary methylmalonic acid excretion and B12 content in tissues. Methionine synthase activity in the testis of the B12-deficient rats was less than 2% of that in B12-supplemented (control) rats. To complement disrupted methionine biosynthesis, methionine was supplied in the diet. A supplement of 5 g D,L-methionine per kg diet to the B12-deficient diet did not affect urinary methylmalonic acid excretion of B12-deficient rats. The testicular histology of rats fed the methionine-supplemented B12-deficient diet was almost indistinguishable from that of control rats. Thus, we conclude that the lowered testicular methionine synthase activity is the primary cause of the histologic damage due to B12-deficiency and that methionine supplementation to the diet can reduce the damage. These findings would indicate the importance of the methionine synthase activity, especially for testicular function.
Assuntos
Suplementos Nutricionais , Metionina/uso terapêutico , Proteínas de Soja/administração & dosagem , Doenças Testiculares/prevenção & controle , Testículo/efeitos dos fármacos , Deficiência de Vitamina B 12/dietoterapia , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/biossíntese , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/efeitos dos fármacos , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Dieta/métodos , Modelos Animais de Doenças , Feminino , Masculino , Ácido Metilmalônico/urina , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Doenças Testiculares/complicações , Doenças Testiculares/patologia , Testículo/fisiopatologia , Testículo/ultraestrutura , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/urinaRESUMO
Osteoarthritis (OA) is a slowly progressing chronic joint disease. Glucosamine (GlcN) is a saccharide that is widely used to relieve symptoms associated with OA. However, the mechanism of the effects of GlcN on articular cartilage remains unclear. We studied the effects of GlcN and its analogues, including chitin derivatives included in health supplements containing GlcN, on a chondrogenic cell line, ATDC5. We examined the effects of these saccharides on the proliferation and differentiation of ATDC5 cells. Glucosamine analogues, such as N-acetyl glucosamine and chitobiose, did not affect the proliferation or differentiation of ATDC5 cells. While GlcN did not affect the proliferation of ATDC5 cells, it inhibited their differentiation. Next, we examined whether GlcN affects mineralization and glycosaminoglycan (GAG) production by ATDC5 cells. Mineralization was markedly inhibited by addition of GlcN to the cell culture medium. Moreover, GlcN induced the formation of sulfated GAG in ATDC5. We also analyzed the mRNA levels in ATDC5 cells. GlcN reduced the mRNA levels of Smad2, Smad4 and MGP. GlcN might inhibit expression of MGP mRNA and induce the production of chondroitin sulfate in ATDC5 cells. The mechanism by which GlcN inhibits mineralization may be by regulating the expression of mRNA for the Smad2 and Smad4 chondrogenic master genes.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Glucosamina/farmacologia , Fosfatase Alcalina/antagonistas & inibidores , Animais , Calcificação Fisiológica/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cartilagem/efeitos dos fármacos , Cartilagem/fisiologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Condrogênese/genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Glucosamina/análogos & derivados , Glucosamina/metabolismo , Glicosaminoglicanos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo , Sulfatos/metabolismo , Proteína de Matriz GlaRESUMO
The cancer-preventive effects of food-derived bovine lactoferrin(bLF), isoflavone-rich soya germ(SG), and spermidine(SPD) on mammary gland carcinogenesis induced by 2-amino-1- methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), were investigated in female Sprague-Dawley(SD) rats. Two hundred and six female SD rats were divided into 8 groups. Cumulative breast cancer incidence at 43 weeks was 65.4% in the PhIP group; 80.0% and 76.0% in the 0.2% and 2.0% bLF groups, respectively; 58.3% and 20.0% in the 2% and 10% SG groups, respectively; and 80.0% and 76.9% in the 0.035% and 0.175% SPD groups, respectively. Isoflavone-rich SG significantly suppressed breast cancer, and the tumors showed fibrous or less malignant features upon histological examination.
Assuntos
Carcinógenos/toxicidade , Glycine max , Imidazóis/toxicidade , Lactoferrina/farmacologia , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Neoplasias Mamárias Experimentais/patologia , Ratos , Ratos Sprague-Dawley , SementesRESUMO
This study was performed to clarify how dietary fiber (DF) with different viscosities would be associated with dietary RNA metabolism. Male Wistar strain rats, four weeks old, were fed diets containing a 3% (w/w) yeast RNA and a 5% (w/w) viscous DF for five days. Viscosity of DF samples used, in order of strength, were xanthan gum (XG) > guar gum (GG) > locust bean gum (LBG) > karaya gum (KG) > pectin (PE) = arabic gum (AG) > CM-cellulose (CMC) = inulin (IN). The serum uric acid concentration in the viscous DF groups significantly decreased as compared with that in the cellulose (CL) group. The urinary excretions of uric acid and allantoin in the respective groups given AG, GG, IN, KG, PE, and XG were significantly suppressed as compared with those in the CL group. The fecal RNA excretion was markedly increased in the IN, KG, PE, and XG groups in comparison to the CL group. The DF with high viscosity significantly suppressed RNA digestion by RNase A and decreased uptakes of 14C-labeled adenosine and adenosine 5'-monophosphate (5'-AMP) in rat jejunum. The results reveal that the suppressive effect of DF on elevation of serum uric acid concentration induced by dietary RNA in rats is associated with the strength of DF viscosity. The mechanism by which this is accomplished is suggested to be attributed to the inhibitions of digestion for dietary RNA and/or absorption of the hydrolyzed compounds.