RESUMO
We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in mid-pregnancy. The association between fatty acids in maternal erythrocytes and mental health risk factors was also examined. Healthy Japanese primiparas in mid-pregnancy (gestational weeks 18-25) were randomly divided into two groups and consumed approximately 2.0 g/day of omega-3 fatty acids in either perilla oil (the ALA dose was 2.4 g/day) or fish oil (the EPA + DHA dose was 1.7 g/day) for 12 weeks. Maternal mental health was assessed using the Edinburgh Postnatal Depression Scale (EPDS) as the primary measure and the Mother-to-Infant Bonding Scale (MIBS) as the secondary measure. Data from an observational study were used as a historical control. Maternal blood, cord blood, and colostrum samples were collected for fatty acid composition analysis. In addition, completers of the observational studies were enrolled in a case-control study, wherein logistic regression analysis was performed to examine the association between maternal fatty acids and EPDS score. The proportion of participants with a high EPDS score (≥9) was significantly lower in the perilla oil group (12.0%, p = 0.044) but not in the fish oil group (22.3%, p = 0.882) compared with the historical control (21.6%), while the proportions between the former groups also tended to be lower (p = 0.059). No marked effect of omega-3 fatty acid intake was observed from the MIBS results. In the case-control study of the historical control, high levels of α-linolenic acid in maternal erythrocytes were associated with an EPDS score of <9 (odds ratio of 0.23, 95% confidence interval: 0.06, 0.84, p = 0.018 for trend). The results of this study suggest that consumption of α-linolenic acid during pregnancy may stabilize postpartum mental health.
Assuntos
Ácidos Graxos Ômega-3 , Feminino , Humanos , Gravidez , Ácido alfa-Linolênico , Estudos de Casos e Controles , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Eritrócitos , Ácidos Graxos , Óleos de Peixe , Saúde Mental , Período Pós-Parto , VitaminasRESUMO
INTRODUCTION: Perinatal women often experience mood disorders and postpartum depression due to the physical load and the rapid changes in hormone levels caused by pregnancy, childbirth, and nursing. When the mother's emotions become unstable, their parental behavior (maternal behavior) may decline, the child's attachment may weaken, and the formation of mother-child bonding can become hindered. As a result, the growth of the child may be adversely affected. The objective of this study was to investigate the effect of ω3 fatty acid deficiency in the perinatal period on maternal behavior and the oxytocin concentration and fatty acid composition in brain tissue. MATERIALS AND METHODS: Virgin female C57BL/6 J mice fed a ω3 fatty acid-deficient (ω3-Def) or adequate (ω3-Adq) diet were mated for use in this study. To assess maternal behavior, nest shape was evaluated at a fixed time from gestational day (GD) 15 to postpartum day (PD) 13, and a retrieval test was conducted on PD 3. For neurochemical measurement, brains were removed from PD 1-6 dams and hippocampal fatty acids and hypothalamic oxytocin concentrations were assessed. RESULTS: Peripartum nest shape scores were similar to those reported previously (Harauma et al., 2016); nests in the ω3-Def group were small and of poor quality whereas those in the ω3-Adq group were large and elaborate. The inferiority of nest shape in the ω3-Def group continued from PD 0-7. In the retrieval test performed on PD 3, dams in the ω3-Def group took longer on several parameters compared with those in the ω3-Adq group, including time to make contact with pups (sniffing time), time to start retrieving the next pup (interval time), and time to retrieve the last pup to the nest (grouping time). Hypothalamic oxytocin concentrations on PD 1-6 were lower in the ω3-Def group than in the ω3-Adq group. DISCUSSION: Our data show that ω3 fatty acid deficiency reduces maternal behavior, a state that continued during pup rearing. This was supported by the observed decrease in hypothalamic oxytocin concentration in the ω3-Def group. These results suggest that ω3 fatty acid supplementation during the perinatal period is not only effective in delivering ω3 fatty acids to infants but is also necessary to activate high-quality parental behavior in mothers.
Assuntos
Dieta/métodos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Comportamento Materno/efeitos dos fármacos , Ocitocina/biossíntese , Núcleo Hipotalâmico Paraventricular/metabolismo , Parto/metabolismo , Período Pós-Parto/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Animais Recém-Nascidos/metabolismo , Feminino , Idade Gestacional , Hipocampo/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Parto/efeitos dos fármacos , Período Pós-Parto/efeitos dos fármacos , GravidezRESUMO
This study aimed to investigate the effects of whey protein hydrolysate (WPH) on the growth and immunity of mouse pups in artificial rearing (AR) system. Mouse pups were reared in the AR system with artificial milk including 5% WPH (AR with WPH) or not (AR without WPH), and the remaining pups were reared by their mother (dam) for 14 days after birth. The body weight change and body weight gain rates in the AR with WPH group were significantly higher than those observed in the AR without WPH group and similar to those in the dam group. Moreover the feed and protein efficiencies in the AR with WPH group were significantly higher than those of the AR without WPH group. In addition, the supplement of WPH in the AR system was shown to significantly elevate the number of CD3+ CD8+ , B220+ CD19+ , IA/IE+ CD11c+ , and CD11b+ in the thymocyte and/or splenocyte, and the thymus weight. Furthermore, MALDI-TOF/MS analysis identified the amino acid sequences corresponding to some peptides, and indicated that VRTPEVDDE had the highest relative intensity among the peptides from tested WPH. Therefore, WPH would be required to not only promote growth, but also exert immunomodulatory activities in mouse pups in AR system.
Assuntos
Ração Animal , Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Dieta/veterinária , Imunomodulação/efeitos dos fármacos , Camundongos/crescimento & desenvolvimento , Camundongos/imunologia , Hidrolisados de Proteína/farmacologia , Proteínas do Soro do Leite , Animais , Antígenos CD/metabolismo , Suplementos Nutricionais , Hidrolisados de Proteína/administração & dosagem , Baço/metabolismo , Timócitos/metabolismoRESUMO
Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), play an important role in biological regulation. In our previous study using mice deficient in Δ6 desaturase (D6D), we reported that ARA is required for body growth, while DHA is necessary for functional development. In mammals, ARA and DHA are supplied directly or by synthesis from linoleic acid (LA) and α-linolenic acid (ALA). However, as desaturase enzyme activity is immature or low in newborns, and humans with minor alleles of the gene encoding desaturase, respectively, they require dietary supplementation with ARA and DHA. To investigate how the body reacts to a long-term reduction in fatty acid synthesis, we measured behavioral changes and fatty acid composition in mice heterozygous for the D6D null mutation with reduced D6D activity fed a diet containing only LA and ALA as PUFAs. During the growth-maturity period, heterozygous mice showed a slightly change in interest and curiosity compared with the wild-type group. ARA levels were decreased in the brain and liver in the heterozygous group, especially during the growth-maturity period, whereas DHA levels were decreased in the liver only in the old age period, suggesting that there are differences in the synthesis of and demand for ARA and DHA during life. For newborns, and humans with minor alleles with low desaturase activity, direct ARA intake is particularly important during the growth-maturity period, but they may need to be supplemented with DHA in the old age period. Further research is needed to determine the optimal intake and duration of these fatty acids.
Assuntos
Ácido Araquidônico/metabolismo , Comportamento Animal , Encéfalo/metabolismo , Dieta/métodos , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Dessaturases/deficiência , Fígado/metabolismo , Animais , Animais Recém-Nascidos , Ansiedade , Suplementos Nutricionais , Ácidos Graxos Dessaturases/genética , Ácido Linoleico/administração & dosagem , Masculino , Camundongos , Camundongos Knockout , Atividade Motora , Ácido alfa-Linolênico/administração & dosagemRESUMO
The essentiality of arachidonic acid (ARA) and docosahexaenoic acid (DHA) for growth and brain function using delta-6-desaturase knockout (D6D-KO) mice and a novel artificial rearing method was investigated. Newborn male wild type (WT) and homozygous D6D-KO pups were separated from their dams within 48h and fed artificial milk containing α-linolenic acid and linoleic acid (Cont), or supplemented with ARA, DHA or both (ARA+DHA). After weaning, each group was fed diets similar to artificial milk in fatty acid composition for 7 weeks. KO-Cont showed a lower body weight than WT-Cont. When ARA was added to the control diet, (KO-ARA and KO-ARA+DHA diets) the body weight gain was restored. The KO-DHA group was initially similar to the WT groups for the first 6 weeks, but afterwards their body weight was significantly lower. Brain weight in the 10 week old KO-ARA+DHA group was significantly higher within the KO dietary groups. Motor activity of the KO-ARA and KO-ARA+DHA groups was elevated relative to the KO-Cont group but the KO-ARA+DHA group exhibited similar activity to the WT-Cont group. In the motor coordination ability test, the KO-Cont group performed significantly worse compared with the WT-Cont group. KO-ARA mice showed decreased motor coordination in spite of their increased motor activity. The best performance was observed in only KO-ARA+DHA mice. These experiments demonstrated that supplementation with only ARA or only DHA was insufficient for optimal development. ARA was essential for normal growth within the lactation period. In conclusion, only the combination of preformed ARA and DHA was capable of improving the dysfunction caused by D6D deficiency.
Assuntos
Ácido Araquidônico/administração & dosagem , Encéfalo/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Graxos Dessaturases/genética , Técnicas de Inativação de Genes , Animais , Animais Recém-Nascidos , Ácido Araquidônico/farmacologia , Peso Corporal/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Ácidos Docosa-Hexaenoicos/farmacologia , Lactação , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Aumento de PesoRESUMO
We previously reported the importance of long-chain polyunsaturated fatty acid (LC-PUFA (>C20)) intake, including arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), for growth. This follow-up study focuses on ARA using a novel artificial rearing model during the lactation period in delta-6-desaturase knockout (D6D-KO) mice. Newborn D6D-KO male mouse pups were separated from dams within 48 hours and fed artificial milks containing 18-C essential fatty acids (EFAs) (16-17% LA, 3.8-4.1% ALA) with or without 1.2% ARA. After weaning, mice were maintained on similar diets: 15% LA, 2.3-2.4% ALA with or without 1.9% ARA. As a reference group, new born wild type (WT) male mouse pups were maintained by artificial milk and diet containing LA and ALA without ARA. Aspects of brain function were measured behaviorally (motor activity and rota-rod test) when mice were age 9 weeks. Body weight in the KO-Cont group was significantly lower (approximately 30%) than in the WT-Cont group, but this decrease was ameliorated by providing ARA in the KO-ARA group. The motor activity and coordination in the KO-Cont group decreased markedly compared to the WT-Cont group. The KO-ARA group had a tendency toward deteriorated motor coordination, although the motor activity was significantly enhanced compared to the KO-Cont group. In KO-ARA group brains, the level of ARA was increased and DHA decreased compared to WT-Cont. These results suggest that intake of LA and ALA only is insufficient to support healthy growth, and that ARA is also required, at least during the lactation period. These findings also suggested that continued intake of relatively high levels of ARA and without supplemental DHA during development led to an increased motor activity above that of WT animals. These studies indicate that both ARA dose and proper combination with DHA must be delineated to define optimal growth and behavioral function.
Assuntos
Ácidos Araquidônicos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Essenciais/administração & dosagem , Animais , Animais Recém-Nascidos , Animais Lactentes , Ácidos Araquidônicos/farmacologia , Peso Corporal/efeitos dos fármacos , Ácidos Graxos Essenciais/farmacologia , Seguimentos , Técnicas de Inativação de Genes , Masculino , Camundongos , Atividade Motora/efeitos dos fármacosRESUMO
The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease.
Assuntos
Ácido Araquidônico/efeitos adversos , Colite/metabolismo , Colo/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/patologia , Peroxidase/metabolismo , Animais , Ácido Araquidônico/metabolismo , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Dieta , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Leucotrieno B4/metabolismo , Macrófagos/metabolismo , Masculino , Ratos Wistar , Tromboxano B2/metabolismoRESUMO
In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function.
Assuntos
Síndromes do Olho Seco/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos/metabolismo , Glândulas Tarsais/química , Animais , Cromatografia Gasosa , Ácidos Docosa-Hexaenoicos/deficiência , Ácidos Graxos/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Camundongos Endogâmicos ICR , Lágrimas/químicaRESUMO
The effect of long-term oral administration of arachidonic acid (ARA, 240 mg/kg/day) on brain function was assessed for mice maintained on an n-3 fatty acid adequate or deficient diet. The administration of ARA for 13 weeks resulted in an elevation of spontaneous motor activity, or the tendency thereof, in both the n-3 fatty acid adequate and deficient groups. However, the n-3 fatty acid deficient mice that were administered with ARA revealed marked deterioration in motor function in a motor coordination test. In the experiment to investigate changes over time, the motor activity of the ARA-administered group continued to increase mildly in n-3 deficient mice, although that of the control group showed a decrease involving habituation for both diet groups from the second week. The fatty acid composition of the brain at the end of the behavioral experiments indicated an increase in the levels of ARA and other n-6 fatty acids, as well as a decrease in the levels of docosahexaenoic acid. These results suggest that long-term administration of ARA causes an increase of futile spontaneous motor activity and the diminution of motor function by aggravation of n-3 fatty acid deficiency.
Assuntos
Ácido Araquidônico/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Neurônios Motores/efeitos dos fármacos , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/metabolismo , Esquema de Medicação , Feminino , Masculino , Camundongos , Neurônios Motores/metabolismoRESUMO
The purpose of this study was to determine the change in tear volume, as a predominant symptom of dry eye syndrome, in dietary n-3 fatty acid deficient mice compared with n-3 fatty acid adequate mice. The tear volume in n-3 fatty acid deficient mice was significantly lower than that in n-3 fatty acid adequate mice. In addition, the concentration of n-3 fatty acid in the lacrimal and meibomian glands, which affects the production of tears, was markedly decreased compared with n-3 fatty acid adequate mice. However, the tear volume recovered almost completely after one week of continuous administration of fish oil containing EPA and DHA in n-3 fatty acid deficient mice. Also, the concentration of DHA in the meibomian gland of n-3 fatty acid deficient group recovered to approximately 80% more than that of n-3 fatty acid adequate group. These results suggested that dietary n-3 fatty acids deficiency showed reversible dry eye syndrome, and that n-3 fatty acids have an important role in the production of tears.
Assuntos
Suplementos Nutricionais , Síndromes do Olho Seco/tratamento farmacológico , Óleos de Peixe/administração & dosagem , Administração Oral , Animais , Ácidos Graxos/sangue , Feminino , Aparelho Lacrimal/metabolismo , Masculino , Glândulas Tarsais/metabolismo , Camundongos Endogâmicos ICR , Retina/metabolismoRESUMO
Decreases in brain docosahexaenoic acid (DHA) have been associated with losses in brain function leading to an interest in the conditions which lead to such brain decreases, and such variables as age. Also of relevance would be the rate of repletion of DHA when the n-3 dietary deficiency is reversed. This experiment describes dietary deficiency in n-3 fatty acids induced in weanling (3 week) and young adult (7 week) mice. There was an immediate and continuous loss of brain DHA with similar rates in the two age groups. Serum DHA declined more rapidly in younger animals with respect to similarly treated adults. Brain and serum docosapentaenoic acid (DPAn-6) increased more rapidly and to higher levels in the younger animals. A second experiment determined the rates of normalization of brain fatty acid profiles when alpha-linolenic acid was added to the diets of n-3 deficient mice. Brain DHA recovery occurred at a faster rate (half-time, T 1/2 = 1.4 weeks) when begun at weaning relative to young adult mice (T 1/2 = 3.5 weeks). Correspondingly, brain DPAn-6 recovered faster in the younger animals; the adult group had a half-time of more than twice that of the 3-week old group. This study therefore demonstrates that the young adult mouse brain DHA is somewhat plastic and can be partially depleted via a low n-3 fatty acid diet and subsequently restored when dietary n-3 fatty acids are repleted. Relevance of these findings for human nutrition is discussed.
Assuntos
Encéfalo/metabolismo , Gorduras Insaturadas na Dieta/metabolismo , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/metabolismo , Fatores Etários , Animais , Peso Corporal , Dieta , Ácidos Graxos/análise , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/sangue , Feminino , Masculino , Camundongos , Tamanho do ÓrgãoRESUMO
Fatty acids and their derivatives play a role in the response to retinal injury. The effects of dietary arachidonic acid (AA) supplementation on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was investigated in young Lewis rats during the gestational, lactational and post-weaning periods. Dams were fed 0·1, 0·5 or 2·0% AA diets or a basal (< 0·01% AA) diet. On postnatal day 21 (at weaning), male pups received a single intraperitoneal injection of 50 mg MNU/kg or vehicle, and were fed the same diet as their mother for 7 d. Retinal apoptosis was analysed by the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick-end labelling (TUNEL) assay 24 h after the MNU treatment, and retinal morphology was examined 7 d post-MNU. Histologically, all rats that received MNU and were fed the basal and 0·1% AA diets developed retinal degeneration characterised by the loss of photoreceptor cells (disappearance of the outer nuclear layer and the photoreceptor layer) in the central retina. The 0·5 and 2·0% AA diets rescued rats from retinal damage. Morphometrically, in parallel with the AA dose (0·5 and 2·0% AA), the photoreceptor ratio significantly increased and the retinal damage ratio decreased in the central retina, compared with the corresponding ratios in basal diet-fed rats. In parallel with the increase in serum and retinal AA levels and the AA:DHA ratio, the apoptotic index in the central retina was dose-dependently decreased in rats fed the 0·5 and 2·0% AA diets. In conclusion, an AA-rich diet during the gestation, lactation and post-weaning periods rescued young Lewis rats from MNU-induced retinal degeneration via the inhibition of photoreceptor apoptosis. Therefore, an AA-enriched diet in the prenatal and postnatal periods may be an important strategy to suppress the degree of photoreceptor injury in humans.
Assuntos
Apoptose/efeitos dos fármacos , Ácido Araquidônico/farmacologia , Suplementos Nutricionais , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Degeneração Retiniana/prevenção & controle , Animais , Ácido Araquidônico/análise , Ácido Araquidônico/sangue , Modelos Animais de Doenças , Feminino , Marcação In Situ das Extremidades Cortadas , Lactação , Metilnitrosoureia , Células Fotorreceptoras de Vertebrados/citologia , Gravidez , Ratos , Ratos Endogâmicos Lew , Retina/patologia , Retina/fisiopatologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologiaRESUMO
Arachidonic acid (AA) is naturally found in human breast milk. AA, together with docosahexaenoic acid, is commonly added as a functional food ingredient to commercial infant formula worldwide, in accordance with the international standard of Codex Alimentarius. However, few studies have been performed that are concerned with the possible carcinogenic effects of AA supplementation during neonatal life. The effect of dietary AA supplementation in dams, during gestation and lactation, was investigated in N-methyl-N-nitrosourea (MNU)-induced preneoplastic lesions in the exocrine pancreas of young Lewis rats. Dams were fed either an AA (2.0% AA) or a basal (<0.01% AA) diet. On postnatal day 0 (at birth), male and female pups received a single intraperitoneal injection of either 35 mg/kg MNU or vehicle. The morphology and proliferating activity of the exocrine pancreas were examined by proliferative cell nuclear antigen immunohistochemistry 7, 14, 21, 28 and/or 60 days post-MNU. Histopathologically, acinar cell hyperplasia (ACH) occurred in the MNU-treated groups 60 days after MNU injection, irrespecitive of whether the rats had been fed an AA diet. Morphometrically, the number and area of ACH per 1 mm(2) in MNU-treated rats increased significantly in the AA diet-fed rats, compared with basal diet-fed rats. The number of proliferative cell nuclear antigen-positive acinar cells in both the normal and hyperplastic areas of MNU-treated rats increased significantly in the AA diet-fed rats. In conclusion, providing dams with an AA-rich diet during gestation and lactation promotes MNU-induced pancreatic ACH in young Lewis rats.
RESUMO
The ability to control the fatty acid content of the diet during early development is a crucial requirement for a one-generation model of docosahexaenoic acid (DHA; 22:6n3) deficiency. A hand feeding method using artificial rearing (AR) together with sterile, artificial milk was employed for feeding mice from postnatal day 2-15. The pups were fed an n-3 fatty acid adequate (3% alpha-linolenic acid (LNA; 18:3n3) + 1% 22:6n3) or a deficient diet (0.06% 18:3n3) with linoleic acid (LA; 18:2n6) as the only dietary source of essential fatty acids by AR along with a dam-reared control group (3.1% 18:3n3). The results indicate that restriction of n-3 fatty acid intake during postnatal development leads to markedly lower levels of brain, retinal, liver, plasma and heart 22:6n3 at 20 weeks of age with replacement by docosapentaenoic acid (DPAn6; 22:5n6), arachidonic acid (ARA; 20:4n6) and docosatetraenoic acid (DTA; 22:4n6). A detailed analysis of phospholipid classes of heart tissue indicated that phosphatidylethanolamine, phosphatidylcholine and cardiolipin were the major repositories of 22:6n3, reaching 40, 29 and 15%, respectively. A novel heart cardiolipin species containing four 22:6n3 moieties is described. This is the first report of the application of artificially rearing to mouse pup nutrition; this technique will facilitate dietary studies of knockout animals as well as the study of essential fatty acid (EFA) functions in the cardiovascular, neural and other organ systems.
Assuntos
Deficiências Nutricionais/etiologia , Ácidos Graxos Ômega-3/metabolismo , Alimentos Formulados/efeitos adversos , Miocárdio/metabolismo , Sistema Nervoso/metabolismo , Ração Animal/efeitos adversos , Criação de Animais Domésticos/métodos , Animais , Animais Recém-Nascidos , Peso Corporal , Deficiências Nutricionais/metabolismo , Deficiências Nutricionais/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Miocárdio/patologia , Sistema Nervoso/patologia , Tamanho do Órgão , Distribuição TecidualRESUMO
We studied the effects of two garlic sources on systolic blood pressure (SBP) using spontaneously hypertensive rats (SHRs). Beginning at 12 wk of age, male SHRs were fed diets containing either aged garlic extract (AGE) or raw garlic (RG) powder for 10 wk. Both AGE and RG reduced the increase of SBP compared with the control group from 4 wk after beginning the experimental diets. The effect of AGE was accompanied by a decrease of pulse pressure (PP), suggesting an improvement of the pliability of the artery, although RG did not affect PP. However, harmful effects were observed in the RG group, including a decrease in erythrocytes, an increase in reticulocytes, and generation of papilloma in the forestomach. These results suggest that AGE may safely improve several factors related to blood vessel physiology and circulatory disease.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Alho , Hipertensão/fisiopatologia , Extratos Vegetais/uso terapêutico , Ração Animal , Animais , Contagem de Células Sanguíneas , Dieta , Modelos Animais de Doenças , Manipulação de Alimentos , Hipertensão/tratamento farmacológico , Masculino , Fitoterapia , Ratos , Ratos Endogâmicos SHR , Estômago/citologia , Estômago/efeitos dos fármacos , Estômago/patologiaRESUMO
Nitric oxide (NO) plays an important role in controlling the physiological functions of the cardiovascular system. However, toxic peroxynitrite is produced by the reaction of NO with superoxide. We investigated the effect of aged garlic extract (AGE) on NO production, and on oxidative stress induced by peroxynitrite. A single dose of AGE temporarily increased NO production by 30-40% between 15 and 60 min after administration to mice. The time course of the fluctuation in NO levels in the AGE-treated group clearly differed from that in a group treated with an inducible NO synthase (iNOS) inducer. A selective constitutive NOS (cNOS) inhibitor overcame the effect of AGE. These results indicate that AGE increases NO production by activating cNOS, but not iNOS. In another experiment, the addition of AGE to a rat erythrocyte suspension reduced the rate of peroxynitrite-induced hemolysis in a concentration-dependent manner, suggesting that AGE protects erythrocytes from membrane damage induced by peroxinitrite. Because an increase in NO derived from cNOS and protection against peroxynitrite are important factors in the prevention of cardiovascular disease, our data strongly suggest that AGE could be useful in preventing cardiovascular diseases associated with oxidative stress or dysfunctions of NO production.
Assuntos
Alho , Hemólise/efeitos dos fármacos , Homeostase/fisiologia , Óxido Nítrico/fisiologia , Extratos Vegetais/farmacologia , Animais , Homeostase/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Ácido Peroxinitroso/metabolismo , Fitoterapia , RatosRESUMO
Docosahexaenoic acid (DHA) is a major structural component of the nervous system, and depletion may lead to losses in neural function. Our objective was to demonstrate a deficit in spatial task performance in rats with low brain DHA due to a low n-3 fatty acid intake using a first-generational artificial rearing technique. Newborn rat pups were separated on d 2 and assigned to two artificial rearing groups or a dam-reared control group. Pups were hand fed artificial milk via custom-designed nursing bottles containing either 0.02% (n-3 Def) or 3.1% (n-3 Adq) of total fatty acids as LNA. At d 21, rats were weaned to either n-3 Def or n-3 Adq pelleted diets and several behavioral tasks were evaluated at 9 wk of age. Brain DHA was lower (58% and 61%, p < 0.001) in n-3 Def in comparison to n-3 Adq and dam-reared rats, respectively. At adulthood, the n-3 fatty acid-deficient rats had a significantly greater moving time than the dam-reared group (p < 0.05), but there were no differences among the three groups in the elevated plus maze test. The n-3 fatty acid deficient rats exhibited a longer escape latency (p < 0.05) and poorer memory retention in the Morris water maze compared with n-3 fatty acid adequate and dam-reared rats. We concluded that artificial rearing can be used to produce n-3 fatty acid deficiency in the first generation. This deficiency was associated with significantly reduced spatial learning. Adequate brain DHA levels are required for optimal spatial learning.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Aprendizagem , Memória , Comportamento Espacial , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Ácido Araquidônico/metabolismo , Peso Corporal , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Feminino , Lipídeos/química , Aprendizagem em Labirinto , Ratos , Ratos Long-Evans , Fatores de TempoRESUMO
Rat pups born to dams fed a diet with 3.1% of total fatty acids as alpha-linolenic acid (LNA) were fed, using an artificial rearing system, either an n-3-deficient (n-3-Def) or an n-3-adequate (n-3-Adq) diet. Both diets contained 17.1% linoleic acid, but the n-3-Adq diet also contained 3.1% LNA. The percentage of brain docosahexaenoic acid (DHA) continuously decreased (71%) with time over the 29 days of the experiment, with concomitant increases in docosapentaenoic acid (DPAn-6). In the retina, the percentage of DHA rose in the n-3-Adq group, with an apparent increased rate around the time of eye opening. However, there was a flat curve for the percentage of DHA in the n-3-Def group and a rising DPAn-6 with time. Liver DHA was highest at the time of birth in the n-3-Adq group but fell off somewhat over the course of 29 days. This decrease was more pronounced in the n-3-Def group, and the DPAn-6 rose considerably during the second half of the experiment. This method presents a first-generation model for n-3 deficiency that is more similar to the case of human nutrition than is the commonly employed two-generation model.
Assuntos
Encéfalo/metabolismo , Gorduras na Dieta/metabolismo , Fígado/metabolismo , Retina/metabolismo , Ácido alfa-Linolênico/metabolismo , Fatores Etários , Animais , Ácido Araquidônico/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Conteúdo Gastrointestinal , Ratos , Ácido alfa-Linolênico/deficiênciaRESUMO
Omega-3 or n-3 fatty acids, especially docosahexaenoic acid, are important structural lipids in the brain. Their deficiency leads to a number of sensory, cognitive and behavioral effects. In previous studies, we showed that n-3 deficiency led to a decrease in the neuronal size of a number of brain regions in young rats. In particular, the neuronal size in the hippocampus CA1-CA3 layers decreased with a slight increase in the volumes of these layers. Therefore, we asked whether fatty acid deficiency could affect rat brain morphology in older animals. To address this question, we carried out gross morphological analysis using Magnetic Resonance Imaging on the gray and white matter volumes of brains in older rats (> 15 months) that were raised on n-3 deficient diets for three generations. We did not detect any differences in the total or regional gray and white matter volumes of brains of old rats maintained on a n-3 deficient or supplemented diet.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Ácidos Graxos Ômega-3 , Envelhecimento , Animais , Feminino , Necessidades Nutricionais , Substância Cinzenta Periaquedutal/anatomia & histologia , Substância Cinzenta Periaquedutal/crescimento & desenvolvimento , Ratos , Ratos Long-EvansRESUMO
Infants fed vegetable oil-based formulas may have poorer visual function, lower cognitive scores and acquire learning tasks more slowly in comparison with those breast fed or those fed formulas supplemented with docosahexaenoate. The aim of the present study was to determine the reversibility of losses in brain function associated with the loss of brain DHA. Rats were fed very low or adequate levels of n-3 fatty acids through three generations. The n-3 fatty acid deficient animals of the F3 generation were then given an n-3 adequate diet containing alpha-linolenic and docosahexaenoic acids (DHA) at birth, weaning (3 weeks) or young adulthood (7 weeks). The spatial task performance of these animals returned to the n-3 adequate diet was then compared using the Morris water at two different ages, at 9 or 13 weeks. Our results indicate that animals repleted since birth or at weaning were able to achieve nearly the same level of brain DHA and spatial task performance as animals maintained for three generations on an n-3 adequate diet. In the case of young adult animals, the degree of DHA and behavioral performance recovery depended upon the duration of dietary repletion with substantial recovery in animals after 6 weeks but little recovery of function after two weeks. The significance of these findings is that they indicate that at least some of the adverse effects of DHA deficiency during neurodevelopment may be reversible with an n-3 fatty acid supplemented diet.