RESUMEN
OBJECTIVE: This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. METHODS: In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. RESULTS: Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine ß-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. CONCLUSION: DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.
Asunto(s)
Dieta , Suplementos Dietéticos , Deficiencia de Ácido Fólico/metabolismo , Homocisteína/metabolismo , Sarcosina/análogos & derivados , Animales , Biomarcadores/metabolismo , Cromatografía Liquida , Hígado/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Sarcosina/administración & dosificación , Sarcosina/metabolismoRESUMEN
OBJECTIVE: To investigate the effects of different level of casein and wheat gluten on decreasing plasma homocysteine concentration in rats. METHODS: 48 rats of the Wistar were fed with different level of casein (12.5%, 25% and 50%) and wheat gluten (14.5%, 29% and 58%) diets for 14 days, and they were killed by decapitation to obtain blood and livers was subject to analysis the concentration of homocysteine, cysteine and other amino acids, as well as BHMT and CBS activities. RESULTS: Body weight gain in rats fed wheat gluten dietary was significantly less than casein dietary, but food intake was significantly decreased in wheat gluten group with increasing of the protein content. The plasma homocysteine concentration in rats fed wheat gluten was marketly less than casein, however plasma cysteine concentration in wheat gluten was higher than casein group. CONCLUSION: The effects of wheat gluten on plasma homocysteine concentration are mainly depends on the low contents of methionine and high cysteine content, but the low contents of lyscine and threonine are not ignored. The mainly mechanism is that the increased cysteine concentration promot enzyme activities of homocystein metabolism, and increase the consumption of homocysteine.
Asunto(s)
Glútenes/metabolismo , Homocisteína/sangre , Aminoácidos , Animales , Caseínas , Cisteína , Dieta , Proteínas en la Dieta , Hígado , Metionina , Proteínas , Ratas , Ratas Wistar , Treonina , TriticumRESUMEN
OBJECTIVE: To investigate the dose-dependent effects of beet powder supplementation on hyperhomocysteinemia induced by choline deprivation in rats. Methods 48 rats of the Wistar were fed 25% soybean protein diet (25S), choline deprivation in 25S diets (25SCD) with different betaine levels (0. 05% and 0. 1%) and beet powder levels (4. 12% and 8. 24%) corresponds to betaine levels for 10 days, and they were killed by decapitation to obtain blood and livers was subject to analysis the concentration of homocysteine, cysteine and other amino acids, as well as BHMT and CBS activities. RESULTS: The homocysteine concentration was increased from (11. 8 ± 0. 4) µmol/L to (33. 2 ± 0. 6) µmol/L by choline deprived - 25S diets (P < 0. 05). The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25S diet was significantly suppressed by 0. 10% betaine or 8. 24% beet in a dose dependent manner. Supplementation with betaine or beet significant increased hepatic BHMT activity. CONCLUSION: The results indicated that betaine or beet could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.
Asunto(s)
Beta vulgaris , Betaína/farmacología , Deficiencia de Colina/complicaciones , Hiperhomocisteinemia/tratamiento farmacológico , Aminoácidos , Animales , Betaína/administración & dosificación , Betaína-Homocisteína S-Metiltransferasa , Colina , Cisteína , Dieta , Suplementos Dietéticos , Homocisteína/sangre , Hiperhomocisteinemia/inducido químicamente , Hígado , Metionina , Ratas , Ratas WistarRESUMEN
Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA) addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25 C) was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S) was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine ß-synthase (CBS) in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.
Asunto(s)
Betaína/administración & dosificación , Deficiencia de Colina/prevención & control , Suplementos Dietéticos , Glicina/análogos & derivados , Hiperhomocisteinemia/prevención & control , Spinacia oleracea , Animales , Deficiencia de Colina/complicaciones , Glicina/toxicidad , Hiperhomocisteinemia/inducido químicamente , Hiperhomocisteinemia/etiología , Masculino , Ratas , Ratas WistarRESUMEN
The effects of dietary supplementation with folate (20 mg/kg diet), 2.5% serine, or both on choline deprivation-induced hyperhomocysteinemia were investigated in rats fed a 10% casein diet (10C) or 25% soybean protein diet (25S) to determine whether folate supplementation with or without serine can suppress choline deficiency-induced hyperhomocysteinemia. Choline deprivation-induced enhancement of plasma homocysteine concentration was significantly suppressed by supplementation with folate, serine, or both, but the effects of these supplements were partial or limited in the rats fed both 10C and 25S. The extents of suppression of plasma homocysteine increments by folate, serine, or both were 29.6, 37.8, and 46.2%, respectively, in rats fed 10C and 27.2, 36.6, and 42.8%, respectively, in rats fed 25S. There was no significant additive effect between folate and serine, a source of C1 units. Folate supplementation with or without serine significantly increased or tended to increase hepatic 5-methyltetrahydrofolate concentration together with methionine synthase (MS) and cystathionine ß-synthase (CBS) activities and MS mRNA level in both rats fed 10C and rats fed 25S. Hepatic betaine-homocysteine S-methyltransferase activity was unaffected by folate with or without serine. Supplementation with serine alone significantly increased hepatic serine concentration and increased or tended to increase CBS activity slightly. It is thought that the suppressive effect of folate on choline deficiency-induced hyperhomocysteinemia was due to increased metabolism of homocysteine via the MS pathway and that the suppressive effect of serine was due to increased metabolism of homocysteine via cystathionine formation. One of the reasons for the insufficient effect of folate alone or in combination with serine is thought to be that the capacity of the MS pathway for homocysteine metabolism is less enhanced by supplementation with folate and serine.
Asunto(s)
Deficiencia de Colina/tratamiento farmacológico , Deficiencia de Colina/metabolismo , Ácido Fólico/farmacología , Hiperhomocisteinemia/tratamiento farmacológico , Hiperhomocisteinemia/metabolismo , Serina/farmacología , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Animales , Betaína-Homocisteína S-Metiltransferasa/genética , Betaína-Homocisteína S-Metiltransferasa/metabolismo , Cistationina betasintasa/genética , Cistationina betasintasa/metabolismo , Suplementos Dietéticos , Hiperhomocisteinemia/sangre , Hígado/enzimología , Hígado/metabolismo , Masculino , ARN Mensajero/química , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Tetrahidrofolatos/sangre , Tetrahidrofolatos/metabolismoRESUMEN
The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only by the MS pathway but also by the BHMT pathway.
Asunto(s)
Betaína/administración & dosificación , Deficiencia de Colina/sangre , Deficiencia de Ácido Fólico/complicaciones , Hiperhomocisteinemia/tratamiento farmacológico , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Animales , Betaína/análisis , Betaína-Homocisteína S-Metiltransferasa/antagonistas & inhibidores , Betaína-Homocisteína S-Metiltransferasa/metabolismo , Suplementos Dietéticos , Inhibidores Enzimáticos/análisis , Ácido Fólico/administración & dosificación , Deficiencia de Ácido Fólico/sangre , Homocisteína/sangre , Hiperhomocisteinemia/sangre , Hígado/química , Hígado/enzimología , Masculino , Ratas , Ratas Wistar , Sarcosina/análogos & derivados , Sarcosina/análisisRESUMEN
The mechanism by which feeding a higher casein diet results in resistance to choline deprivation-induced hyperhomocysteinemia was investigated in rats. Plasma homocysteine concentration was significantly lower in rats fed a 30% casein diet (30C) than in rats fed a 10% casein diet (10C). Choline deprivation did not enhance plasma homocysteine concentration in rats fed 30C, while it significantly enhanced plasma homocysteine concentration in rats fed 10C. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 10C was significantly suppressed by methionine supplementation in a dose-dependent manner in the range of 0.1 to 0.3%, but the suppressive effect of methionine became smaller with an increase in supplementation level in the range of 0.3 to 0.5%. At a 0.5% supplementation level, methionine did not exhibit any suppressive effect on choline deprivation-induced hyperhomocysteinemia. The higher plasma homocysteine concentration in rats fed choline-deprived 10C+0.5% methionine was significantly decreased by concurrent supplementation with 0.32% glycine+0.94% serine to the level of rats fed 10C. Raising dietary total amino acid level by adding 3.61% branched-chain amino acids (BCAA)+4.5% acidic amino acids (AAA) to choline-deprived 10C+0.5% methionine+0.32% glycine+0.94% serine resulted in a further decrease in plasma homocysteine concentration to a level lower than the level in rats fed 10C. Choline deprivation-induced increases in hepatic S-adenosylhomocysteine and homocysteine concentrations were significantly suppressed by supplementation with glycine+serine and further suppressed by BCAA+AAA. Hepatic cystathionine ß-synthase activity and its gene expression were significantly increased by BCAA+AAA. Hepatic triglyceride concentration changed in a manner similar to that of plasma homocysteine concentration. The results indicate that there are at least three factors contributing to the resistivity of rats fed a higher casein diet (30C) to choline deprivation-induced hyperhomocysteinemia, i.e., higher intake of methionine, higher intake of glycine and serine, and higher intake of other amino acids such as BCAA and AAA.
Asunto(s)
Caseínas/administración & dosificación , Deficiencia de Colina/complicaciones , Dieta , Hiperhomocisteinemia/etiología , Animales , Colina/administración & dosificación , Glicina/administración & dosificación , Homocisteína/sangre , Masculino , Metionina/administración & dosificación , Ratas , Ratas Wistar , Serina/administración & dosificaciónRESUMEN
The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10% casein diet. Hyperhomocysteinemia induced by choline deprivation was not suppressed by methionine alone and was only partially suppressed by serine alone, whereas it was completely suppressed by a combination of methionine and serine, suggesting a synergistic effect of methionine and serine. Fatty liver was also completely prevented by the combination of methionine and serine. Compared with methionine alone, the combination of methionine and serine decreased hepatic S-adenosylhomocysteine and homocysteine concentrations and increased hepatic betaine and serine concentrations and betaine-homocysteine S-methyltransferase activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine alone, but no interacting effect of methionine and serine was detected. In contrast, GAA-induced fatty liver was completely prevented by the combination of methionine and serine. These results indicate that a combination of methionine and serine is effective in suppressing both hyperhomocysteinemia and fatty liver induced by choline deprivation, and that methionine alone is effective in suppressing GAA-induced hyperhomocysteinemia partially.
Asunto(s)
Caseínas/metabolismo , Colina/metabolismo , Dieta , Glicina/análogos & derivados , Hiperhomocisteinemia/tratamiento farmacológico , Metionina/farmacología , Serina/farmacología , Animales , Dieta/efectos adversos , Suplementos Dietéticos , Sinergismo Farmacológico , Glicina/efectos adversos , Hiperhomocisteinemia/inducido químicamente , Hiperhomocisteinemia/metabolismo , Masculino , Metionina/uso terapéutico , Ratas , Ratas Wistar , Serina/uso terapéuticoRESUMEN
We attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D-galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n-hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n-hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3',4',5,6,7,8-hexamethoxyflavanone (citromitin), 4',5,6,7,8-pentamethoxyflavone (tangeretin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n-hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-alpha and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-alpha and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Citrus/química , Flavonas/uso terapéutico , Flavonoides/uso terapéutico , Hígado/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Acetaminofén , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Fragmentación del ADN/efectos de los fármacos , Flavonas/farmacología , Flavonoides/farmacología , Galactosamina , Lipopolisacáridos , Hígado/enzimología , Masculino , Estructura Molecular , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangreRESUMEN
To evaluate the protective effects of fruit juices against D-galactosamine (GalN)-induced liver injury, lyophilized fruit juices (total 12 kinds) were fed to rats for 7 d, and then we evoked liver injury by injecting GalN. The juice of camu-camu (Myrciaria dubia) significantly suppressed GalN-induced liver injury when the magnitude of liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, although some other juices (acerola, dragon fruit, shekwasha, and star fruit) also tended to have suppressive effects. An active compound was isolated from camu-camu juice by solvent fractionation and silica gel column chromatography. The structure was determined to be 1-methylmalate. On the other hand, malate, 1,4-dimethylmalate, citrate, and tartrate had no significant effect on GalN-induced liver injury. It is suggested that 1-methylmalate might be a rather specific compound among organic acids and their derivatives in fruit juices in suppressing GalN-induced liver injury.
Asunto(s)
Bebidas , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Frutas/química , Malatos/uso terapéutico , Myrtaceae/química , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Ácido Cítrico/aislamiento & purificación , Galactosamina/toxicidad , Malatos/aislamiento & purificación , Masculino , Ratas , Ratas Wistar , Tartratos/aislamiento & purificaciónRESUMEN
We examined the role of soluble fiber viscosity in small intestinal mucin secretion. Viscosities were defined as the area under the viscosity curve (VAUC). Rats were fed a control diet or diets containing konjac mannan (KM) [low, medium, or high molecular weight (LKM, MKM, HKM), respectively] at 50 g/kg diet for 10 d. Luminal mucin content and goblet cell number increased in proportion to the molecular weight of KM. Such effects with the HKM diet were nullified by the concurrent ingestion of 2 g cellulase/kg diet. Diet containing LKM, MKM, HKM, guar gums (high or low molecular weight; HGG, LGG), psyllium (PS), or pectin (PC) at 50 g/kg was fed to rats. Fibers with higher VAUC (MKM, HKM, HGG, and PS) increased goblet cell numbers, but not those with lower VAUC (LKM, LGG, and PC). Luminal mucins were greater in rats fed HKM, PC, and PS diets. Goblet cell numbers and VAUC were correlated (r = 0.98; P < 0.01). In rats fed the HKM diet, ileal Muc2 gene expression was not affected, but that of Muc3 was lower than in those fed the control diet, indicating that the increase in luminal mucins after ingestion of HKM diet occurred independently of enhanced Muc gene expression. An incorporation study of 5'-bromo-deoxyuridine (BrdU) showed the position of the uppermost-BrdU labeled cell along the villi was higher in rats fed the HKM diet than in those fed the control diet. The results suggest that soluble fibers, except PC, upregulate baseline secretion of luminal mucins by increasing goblet cell numbers in proportion to fiber VAUC.
Asunto(s)
Carbohidratos de la Dieta/farmacología , Fibras de la Dieta/farmacología , Expresión Génica/efectos de los fármacos , Células Caliciformes/efectos de los fármacos , Íleon/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucinas/metabolismo , Amorphophallus , Animales , Bromodesoxiuridina/metabolismo , Celulasa/farmacología , Dieta , Células Epiteliales/efectos de los fármacos , Galactanos/farmacología , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Mananos/farmacología , Mucina 3/genética , Mucina 3/metabolismo , Mucinas/genética , Pectinas/farmacología , Gomas de Plantas/farmacología , Poliestirenos/farmacología , Psyllium/farmacología , Ratas , Ratas Wistar , Solubilidad , ViscosidadRESUMEN
To elucidate the mechanism by which moderate and high protein diets fail to increase plasma homocysteine concentration despite dietary methionine levels being higher, rats were fed diets with graded levels (10, 30, and 50%) of casein or low casein diets supplemented with methionine at levels of 0.5 and 1.0% together with or without glycine+serine, which corresponded to moderate and high casein diets with respect to these amino acids, for 14 d. The plasma homocysteine concentration significantly decreased with an increase in dietary casein level, whereas it significantly increased with an increase in dietary methionine level when the low casein diet was supplemented with methionine. Supplementation with glycine+serine significantly suppressed the elevation of plasma homocysteine concentration due to methionine supplementation, but it could not decrease plasma homocysteine concentration to the levels in rats fed corresponding casein diets. Increased concentrations of hepatic S-adenosylhomocysteine and homocysteine due to methionine supplementation were also significantly suppressed by glycine+serine. The activity of hepatic cystathionine beta-synthase (CBS) did not increase in response to methionine supplementation, while it significantly increased with an increase in dietary casein level. In contrast, the activity of hepatic betaine-homocysteine S-methyltransferase (BHMT) significantly increased with increase in both dietary casein level and dietary methionine level. Hepatic levels of mRNA for CBS and BHMT were parallel to the enzyme activities. The results suggest that, in contrast to methionine-supplemented low casein diets, moderate and high casein diets avoid increasing plasma homocysteine concentration through dual mechanisms, greater supply of glycine+serine and an increase in CBS activity.
Asunto(s)
Betaína-Homocisteína S-Metiltransferasa/metabolismo , Caseínas/farmacología , Cistationina betasintasa/metabolismo , Glicina/farmacología , Homocisteína/sangre , Metionina/farmacología , Serina/farmacología , Animales , Cisteína/sangre , Proteínas en la Dieta/farmacología , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Ingestión de Energía , Hígado/enzimología , Hígado/metabolismo , Masculino , Metionina/metabolismo , Tamaño de los Órganos , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , S-Adenosilhomocisteína/sangre , S-Adenosilmetionina/metabolismo , Aumento de PesoRESUMEN
Experiments were conducted to clarify the relationship between dietary protein level and plasma homocysteine concentration in rats. Male Wistar rats were fed diets differing in casein level from 5 to 50% for 14 d (Expt. 1). Plasma total homocysteine concentration was positively correlated with dietary casein level in the range of 5 to 10% but inversely correlated with dietary casein level in the range of 10 to 50%. Hepatic cystathionine beta-synthase (CBS) and betaine-homocysteine S-methyltransferase (BHMT) activities and renal CBS activity increased in response to dietary casein level in the range of 10 to 50%, whereas hepatic serine and betaine concentrations decreased with increasing dietary casein levels. When rats were fed the 10% casein diet or 10% casein+17.2% amino acid mixture diet for 14 d, plasma homocysteine concentration was significantly lower in rats fed the amino acid mixture-added diet than in rats fed the 10% casein diet (Expt. 2), indicating that the hypohomocysteinemic effect of high casein diets was elicited by amino acids, not by casein contaminants. The degree of increase in plasma homocysteine concentration caused by dietary supplementation with 0.75% L-methionine was significantly lower in rats fed the 40% casein diet than in rats fed the 10% casein diet (Expt. 3). These results indicate that high casein diets do not increase but rather decrease plasma homocysteine concentration and cause resistance to hyperhomocysteinemic treatment, and suggest that such effects of high casein diets are mediated at least by increased activities of CBS and BHMT.
Asunto(s)
Betaína-Homocisteína S-Metiltransferasa/metabolismo , Caseínas/farmacología , Cistationina betasintasa/metabolismo , Homocisteína/sangre , Hiperhomocisteinemia/prevención & control , Aminoácidos/farmacología , Animales , Betaína/metabolismo , Caseínas/administración & dosificación , Dieta , Relación Dosis-Respuesta a Droga , Masculino , Metionina/farmacología , Ratas , Ratas Wistar , Serina/metabolismoRESUMEN
Rats were fed diets with and without 0.5% L-cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C+0.65% methionine or 25C+0.4% guanidinoacetic acid. Hepatic S-adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine beta-synthase and betaine-homocysteine S-methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine.
Asunto(s)
Cisteína/sangre , Cisteína/farmacología , Dieta con Restricción de Proteínas , Homocisteína/metabolismo , Hiperhomocisteinemia/prevención & control , Metionina/administración & dosificación , Animales , Betaína-Homocisteína S-Metiltransferasa/metabolismo , Caseínas/farmacología , Colina/farmacología , Cistationina betasintasa/metabolismo , Ácido Cisteico/farmacología , Cisteína/uso terapéutico , Suplementos Dietéticos , Glicina/análogos & derivados , Glicina/farmacología , Masculino , Mercaptoetilaminas/farmacología , Metionina/farmacología , Ratas , Ratas Wistar , S-Adenosilhomocisteína/metabolismo , Proteínas de Soja/farmacologíaRESUMEN
Anti-inflammatory effects of short-chain inulin-like fructans (SCF) on trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated in rats, focusing specifically on endotoxin and bacterial translocations. SCF with degrees of polymerization (DP) of 4 and 8 were used. Rats were fed either control diet or diets including 60 g DP4 or DP8 per kilogram for 7 days, and then received intracolonic TNBS and were fed the respective diets for a further 10 days. DP4 and DP8 significantly reduced colonic injuries as assessed by damage score, but the reduction of colonic myeloperoxidase activity was manifest solely with DP8. At 3 days after colitis induction, bacterial translocation to the mesenteric lymph node was significantly lower in the DP4 and DP8 groups, but significant reduction in the portal endotoxin concentration was achieved solely in the DP8 group. Immediately prior to colitis induction, cecal immunoglobulin A and mucin concentrations were higher in the DP4 and DP8 groups, but these changes were abolished at 10 days post colitis induction. The data suggest that SCF exert prophylactic effects against TNBS colitis, presumably as a result of inhibitory effects on endotoxin and bacterial translocations.
Asunto(s)
Traslocación Bacteriana/efectos de los fármacos , Colitis/microbiología , Endotoxinas/metabolismo , Fructanos/farmacología , Animales , Ciego/metabolismo , Colitis/inducido químicamente , Colitis/prevención & control , Fermentación , Fructanos/química , Concentración de Iones de Hidrógeno , Inmunoglobulina A/metabolismo , Ganglios Linfáticos/microbiología , Masculino , Mesenterio , Mucinas/metabolismo , Polímeros , Ratas , Ratas Endogámicas F344 , Ácido TrinitrobencenosulfónicoRESUMEN
To determine the effect of dietary protein level on experimental hyperhomocysteinemia, rats were fed 10% casein (10C) and 40% casein (40C) diets with or without 0.5% guanidinoacetic acid (GAA) for 14 d. In addition, rats were fed 10C + 0.75% methionine (10CM) and 40C + 0.75% methionine (40CM) diets with or without 2.5% serine for 14 d to determine the relationship between the dietary protein level and intensity of the hypohomocysteinemic effect of serine. GAA supplementation markedly increased the plasma homocysteine concentration in rats fed with the 10C diet, whereas it did not increase the plasma homocysteine concentration in rats fed with the 40C diet. Although serine supplementation significantly suppressed the methionine-induced enhancement of plasma homocysteine concentration, the decreased plasma homocysteine concentration was significantly lower in rats fed with the 40CM diet than in rats fed with the 10CM diet. The hepatic cystathionine beta-synthase and betaine-homocysteine S-methyltransferase activities were significantly higher in rats fed with the 40C or 40CM diet than in rats fed with the 10C or 10CM diet, irrespective of supplementation with GAA and serine. These results indicate that the high-casein diet was effective for both suppressing GAA-induced hyperhomocysteinemia and potentiating the hypohomocysteinemic effect of serine, probably through the enhanced activity of homocysteine-metabolizing enzymes.
Asunto(s)
Caseínas/farmacología , Dieta , Glicina/análogos & derivados , Hiperhomocisteinemia/inducido químicamente , Serina/farmacología , Animales , Caseínas/uso terapéutico , Cisteína/sangre , Glicina/toxicidad , Homocisteína/sangre , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/tratamiento farmacológico , Hiperhomocisteinemia/metabolismo , Masculino , Metionina/metabolismo , Metionina/farmacología , Ratas , Ratas WistarRESUMEN
Rats were fed diets supplemented with 1% L-methionine with and without 2.5% various amino acids for 7 d to determine what amino acids other than glycine, serine, and cystine can suppress methionine-induced hyperhomocysteinemia. L-Glutamic acid, L-histidine, and L-arginine significantly suppressed methionine-induced enhancement of plasma homocysteine concentrations, but the mechanisms underlying the effect of these amino acids are thought not to be identical.
Asunto(s)
Aminoácidos/farmacología , Hiperhomocisteinemia/tratamiento farmacológico , Animales , Arginina/farmacología , Suplementos Dietéticos , Ácido Glutámico/farmacología , Histidina/farmacología , Homocisteína/sangre , Hiperhomocisteinemia/inducido químicamente , Metionina , RatasRESUMEN
Rats were fed 25% casein (25C) diets differing in choline levels (0-0.5%) with and without 0.5% guanidinoacetic acid (GAA) or 0.75% L-methionine for 7 d to determine the effects of dietary choline level on experimental hyperhomocysteinemia. The effects of dietary choline (0.30%) and betaine (0.34%) on GAA- and methionine-induced hyperhomocysteinemia were also compared. Dietary choline suppressed hyperhomocysteinemia induced by GAA, but not by methionine, in a dose-dependent manner. GAA-induced enhancement of the plasma homocysteine concentration was suppressed by choline and betaine to the same degree, but the effects of these compounds were relatively small on methionine-induced hyperhomocysteinemia. Dietary supplementation with choline and betaine significantly increased the hepatic betaine concentration in rats fed a GAA diet, but not in rats fed a methionine diet. These results indicate that choline and betaine are effective at relatively low levels in reducing plasma homocysteine, especially under the condition of betaine deficiency without a loading of homocysteine precursor.
Asunto(s)
Betaína/farmacología , Colina/farmacología , Hiperhomocisteinemia/tratamiento farmacológico , Animales , Betaína/uso terapéutico , Colina/uso terapéutico , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Glicina/efectos adversos , Glicina/análogos & derivados , Homocisteína/sangre , Hiperhomocisteinemia/inducido químicamente , Hígado/química , Metionina/efectos adversos , RatasRESUMEN
There was an inverse correlation between the plasma homocysteine concentration and dietary protein level or protein intake when a soybean protein isolate (SPI) was used as a protein source for rats. The hepatic cystathionine beta-synthase activity increased in response to the dietary SPI level. The results suggest that a high-protein diet might be an effective means to lower the plasma homocysteine concentration, probably through enhancement of the homocysteine-metabolizing activity.
Asunto(s)
Homocistina/sangre , Proteínas de Soja/farmacología , Animales , Peso Corporal/efectos de los fármacos , Masculino , Ratas , Ratas WistarRESUMEN
We reexamined the hypothesis that increased mucin secretion by the ingestion of insoluble dietary fiber (IDF) could affect small intestinal nutrient absorption. Polystyrene foam (PSF) was used as IDF. Rats were fed a diet with or without 90 g of PSF/kg for 1, 2 and 4 wk. At the end of each period, a glucose and ovalbumin (OVA) solution was intubated after 12 h of food depletion, and the changes in serum concentrations of these components were monitored. Luminal mucin was measured as O-linked oligosaccharide chains and also determined by ELISA. In all periods, the luminal mucin content was greater in the PSF-fed group than in the fiber-free control. However, the changes in serum glucose and OVA concentrations were comparable between the groups at any time during any period. These results show that the enhancement of luminal mucin secretion lasted even after chronic ingestion of IDF, but that the increased luminal mucin content had no effect on the rate of luminal nutrient absorption.