Role of ω3 polyunsaturated fatty acids in diabetic retinopathy: a morphological and metabolically cross talk among blood retina barriers damage, autoimmunity and chronic inflammation.

Vision disorders are one of the most serious complications of diabetes mellitus (DM) affecting the quality of life of patients and eventually cause blindness. The ocular lesions in diabetes mellitus are located mainly in the blood vessels and retina layers. Different retina lesions could be grouped under the umbrella term of diabetic retinopathies (DMRP).We propose that one of the main causes in the etiopathogenesis of the DMRP consists of a progressive loss of the selective permeability of blood retinal barriers (BRB). The loss of selective permeability of blood retinal barriers will cause a progressive autoimmune process. Prolonged autoimmune injures in the retinal territory will triggers and maintains a low-grade chronic inflammation process, microvascular alterations, glial proliferation and subsequent fibrosis and worse, progressive apoptosis of the photoreceptor neurons.Patients with long-standing DM disturbances in retinal BRBs suffer of alterations in the enzymatic pathways of polyunsaturated fatty acids (PUFAs), increase release of free radicals and pro-inflammatory molecules and subsequently incremented levels of vascular endothelial growth factor. These facts can produce retinal edema and photoreceptor apoptosis.Experimental, clinical and epidemiological evidences showing that adequate metabolic and alimentary controls and constant practices of healthy life may avoid, retard or make less severe the appearance of DMRP. Considering the high demand for PUFAs ω3 by photoreceptor complexes of the retina, it seems advisable to take fish oil supplements (2 g per day). The cellular, subcellular and molecular basis of the propositions exposed above is developed in this article.Synthesizer drawings the most relevant findings of the ultrastructural pathology, as well as the main metabolic pathways of the PUFAs involved in balance and disbalanced conditions are provided.

Diabetic encephalopathy: beneficial effects of supplementation with fatty acids ω3 and nordihydroguaiaretic acid in a spontaneous diabetes rat model.

BACKGROUND: Diabetic encephalopathy is a chronic complications of diabetes mellitus that affects the central nervous system. We evaluated the effect of ω3 and ω6 polyunsaturated fatty acids (PUFAs) supplementation plus the antioxidant agent nordihydroguaiaretic acid (NDGA) on the etiopathology of diabetic encephalopathy in eSS rats, a spontaneous model of type 2 diabetes. METHODS: One hundred twenty spontaneous diabetic eSS male rats and 38 non-diabetic Wistar, used as healthy control, received monthly by intraperitoneal route, ω3 or ω6 PUFA (6.25 mg/kg) alone or plus NDGA (1.19 mg/kg) for 12 months. Diabetic rats had a worse performance in behavioural Hole-Board test. Histopathological analysis confirmed lesions in diabetic rats brain tissues. We also detected low expression of synaptophysin, a protein linked to release of neurotransmitters, by immunohistochemically techniques in eSS rats brain. Biochemical and histopathological studies of brain were performed at 12th month. Biochemical analysis showed altered parameters related to metabolism. High levels of markers of oxidative stress and inflammation were detected in plasma and brain tissues. Data were analysed by ANOVA test and paired t test was used by comparison of measurements of the same parameter at different times. RESULTS: The data obtained in this work showed that behavioural, biochemical and morphological alterations observed in eSS rats are compatible with previously reported indices in diabetic encephalopathy and are associated with increased glucolipotoxicity, chronic low-grade inflammation and oxidative stress burden. Experimental treatments assayed modulated the values of studied parameters. CONCLUSIONS: The treatments tested with ω3 or ω3 plus NDGA showed improvement in the values of the studied parameters in eSS diabetic rats. These observations may form the basis to help in prevent and manage the diabetic encephalopathy.

Differential Potentiation of Retinoic Acid Effects against Human Breast Cancer Cells by Unsaturated Fatty Acids.

Retinoic acid (RA) and unsaturated fatty acids (UFA) are proposed as nutritional anticancer agents. Nonetheless, the activity of their combination on human breast cancer needs further study. Our aim was to evaluate this activity on the MCF-7 and ZR-75-1 cell lines treated with 1 µM RA and 50 µM of γ-linoleic (GLA, ω-6), eicosapentaenoic (EPA, ω-3), oleic (OA, ω-9), or eicosatrienoic (ETA, ω-9) acids. The following cellular responses were compared by ANOVA and Fisher test (P < 0.05): fatty acids, E-cadherin, actin (differentiation), conjugated dienes, γ-glutamyltranspeptidase activity (stress), and viability, which were correlated by partial least squares regression. Although both cell lines responded differentially, RA modified unsaturated fatty acids, increased differentiation, reduced γ-glutamyltranspeptidase, and viability. RA differentiating activity on ZR-75-1 was morphologically enhanced by UFA. Stress induction with γ-glutamyltranspeptidase decrease and conjugated dienes was promoted by ETA in MCF-7, and EPA and OA in ZR-75-1. RA-related reduced viability was potentiated by EPA and OA in both lines. GLA was less active. Therefore, unsaturated fatty acids (ω-3/ω-9) potentiated the multitarget retinoic acid activity against these human breast cancer cells.

Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid.

Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.

Delay of Lung Adenocarcinoma (LAC-1) Development in Mice by Dietary Oleic Acid.

Lung cancer is the leading cause of death by cancer, and is a major sanitary concern worldwide. Some nutrients, such as ω-9 fatty acids, have been proposed as anticancer agents. Thus, an olein-enriched diet was assayed in a murine model of lung adenocarcinoma (LAC-1) to evaluate neoplastic and paraneoplastic evolution in BALB/c mice. The organic assimilation of dietary fatty acids was confirmed in liver by gas chromatography. This experimental oleic acid-containing diet increased animal survival and tumour latency (analysed by the Kaplan-Meier method), improving neoplastic evolution and general status, with weak effects on the paraneoplastic syndrome (thymus atrophy, splenomegaly, splenocyte response to mitogen, blood anaemia, and leucocytosis). Tumour lipid oxidation was not involved. Thus, diet enrichment with olein, a natural source of the ω-9 oleic acid, significantly delayed progression of LAC-1 and increased tumour latency and mice survival. These results support its use in nutritional management of cancer, with further studies being encouraged.

Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis.

OBJECTIVE: The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma. MATERIALS AND METHODS: BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma. RESULTS: After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERß in tumor lysates. CONCLUSION: These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

BACKGROUND: Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. METHODS: After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. RESULTS: Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. CONCLUSIONS: eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

Effect of arsenite on nitrosative stress in human breast cancer cells and its modulation by flavonoids.

Arsenic (As) is used in the treatment of leukemia and breast cancer due to its oxidative cytotoxic action. However, it is also toxic to normal cells. One proposed anticancer mechanism induced by As might be nitrosative stress (NS). It is believed that antioxidant flavonoids in combination with As might reduce its toxic action on normal cells without interfering with its antitumor action. In the present study, we evaluated the antineoplastic potential of As on breast human cancer lines MCF-7 and ZR-75-1 treated with redox-modulating flavonoids, such as quercetin (Q) and silymarin (S). Even though both cell lines differed about their oxidative responsiveness, their viability was decreased by NS induction through γ-glutamyltranspeptidase inhibition. Arsenic triggered NS in both MCF-7 and ZR-75-1 cultures, with the formers more sensitive without recovering their pre-treatment capacity. ZR-75-1 cells maintained their antioxidant status, whereas MCF-7 ones treated with S, As, and As + Q did not. Silymarin did not interfere with the described As bioactivity. NS was an anticancer mechanism exerted by As depending on the redox cellular response that could be differentially modified by dietary antioxidants. Hence, it is worthwhile to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy, especially when using As.

Characterization of a murine lung adenocarcinoma (LAC1), a useful experimental model to study progression of lung cancer.

Lung cancer is one of the most important avoidable causes of death around the world, the most widespread carcinoma, with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. We report morphological and biological behavior characteristics of a tumor that arose in only one BALB/c mouse of an experimental group treated with urethane, a chemical lung-tumorigenic agent. Morphological and immunochemical analysis indicated phenotypic compatibility with a lung adenocarcinoma. The tumor was named LAC1 (lung adenocarcinoma 1). Implant success in eight LAC1-bearing mice generations was 100%, with a fast evolution (58 survival days) and good metastatic capacity (41% of animals with metastases). The tumor induced a paraneoplastic syndrome characterized by anemia, neutrophilia, cachexia, splenomegaly and thymic atrophy. The lymphoproliferation to Con A was altered in tumor-bearing mice. This lung adenocarcinoma may be a useful experimental model for studying tumor progression, paraneoplastic syndromes and immunology in carcinogenic studies.

Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model.

BACKGROUND: Nutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet. RESULTS: Peanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups. CONCLUSIONS: The results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities.

Assessment of colorectal cancer prognosis through nuclear morphometry.

BACKGROUND: Due to the fact that different biological parameters play a key role in colonic malignant behavior, with nuclear morphometry being a prognostic marker in many malignancies, then predictive approaches in colorectal cancer (CRC) carried out on histologically well-defined groups may prevent interpretative errors. Subsequently, in the present study, CRC patients were screened according to the morphometric features of tumor cell nuclei, using an accurate histotechnical approach, to analyze their clinical evolution according to Dukes' stratification. MATERIALS AND METHODS: A total of 66 cases were grouped according to Dukes' classification (5 y of follow-up). The perimeter, nuclear area, and shape factor of 50 interphase carcinoma nuclei were recorded through microphotographs obtained from each subject. Nuclei boundaries were drawn by an electronic pencil and examined by a computerized system. Data were submitted to a variance analysis, and a multi-regression model compared results. RESULTS: The sample was made up of 44 males (66.67%) and 22 females (33.33%) aged 59.7 +/- 6 y old. Forty-nine patients (74.24%) were classified as stage B, and 17 (25.76%) as stage C. Nuclear homogeneity was confirmed by analysis of variance. The nuclear parameters were (mean +/- SD): area (3.17 +/- 1.74), perimeter (6.72 +/- 1.83), and shape factor (0.82 +/- 0.03). A multiple logistic regression model showed that stage C subjects had a higher risk of developing a worse clinical evolution than those at stage B (P < 0.02), independent of sex and age. CONCLUSIONS: Dukes' classification remains the best predictor of evolution. Although nucleomorphometric suitability is still controversial, this technique has become an additional tool to establish CRC prognosis.

Subchronic toxicological evaluation of brea gum (Parkinsonia preacox) as a food additive in BALB/c mice.

Brea gum is a phloematic exudate from Parkinsonia praecox, an autoctonous tree that grows in the arid areas of Argentina. In this work, we propose its potential as a food additive. However, as no toxicological safety evaluation of brea gum has yet been reported, this preliminary study was conducted to evaluate its long-term toxicity over a 120-day period in BALB/c mice fed with brea gum at various levels in the diet. The results showed that animals on diets containing up to 5% brea gum were healthy, exhibiting growth curves similar to controls for both males (P = 0.9138) and females (P = 0.9459), thereby indicating that feed intake and utilization was not affected. A histopathological examination and weight recording of liver, kidneys, and intestine did not reveal any microscopic abnormalities or adverse toxicological effect (weights respect to control: P > 0.1). Moreover, hematological parameters and enzyme activities were within the normal values previously reported for mice. Our findings suggest that feeding brea gum at levels up to 5% to BALB/c mice do not exert any toxicological effects, supporting its potential use as a food additive for human consumption.

Differential effects of quercetin and silymarin on arsenite-induced cytotoxicity in two human breast adenocarcinoma cell lines.

Arsenic has been proposed as a chemotherapeutic agent for leukemia and other solid tumors. However, its environmental exposure has been linked epidemiologically with an elevated carcinoma risk (i.e. skin, bladder and lung), with cellular oxidative stress being implicated in both induced-arsenic toxicity and carcinogenicity. Consequently, antioxidants may differentially interfere in these effects. The human mammary adenocarcinoma lines MCF-7 and ZR-75-1 were treated in vitro with 200 microM NaAsO(2) (As), 5 microM silymarin (S) and/or 50 microM quercetin (Q). The following biomembrane parameters were assessed: sialic acid (SA) in gangliosides, gamma-glutamyltranspeptidase activity (GGT), conjugated dienes and free radical activity, in order to evaluate the arsenite-flavonoid interactions. The time-dependent arsenite toxicity was not prevented by flavonoids in ZR-75-1 cells, whereas quercetin protected MCF-7 cells for 8 h. With regard to GGT, only quercetin protected ZR-75-1 cells against stress. In MCF-7 cells, the arsenite-induced GGT activity was not counteracted by either quercetin or silymarin. S, Q, As and As + S treatments reduced the SA content only in the MCF-7 membrane, while As + Q treatment increased it in both lines. The membrane resistance to lipid oxidation in these cells enclosed the up-regulation of GGT activity and sialylglycolipid content. Taking these results together, quercetin interfered with arsenite toxicity, whereas silymarin was not able. Thus, the potential role of flavonoids as co-adjutants may differ widely in therapeutic protocols.

Dietary n-3 polyunsaturated fatty acids improve endothelial markers in metabolic syndrome: A systematic review

ABSTRACT Metabolic syndrome (MS) is a global health problem. Dietary factors, especially fatty acids, may affect MS pathology. However, the associations between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and MS risk demonstrate inconsistent results. To clarify the relationship between dietary n-3 PUFA and endothelial function on MS, we carried out a systematic review. An electronic literature search based on controlled clinical trials (CCTs) between 2004 and 2020 was conducted. A total of 28 articles were included in the systematic review. Studies were analyzed according intervention type: dietary interventions (12 CCTs), dietary supplementation interventions (9 CCTs) and mixed interventions (7 CCTs). Studies with dietary interventions characterized by n-3 PUFAs increased by food source, such as Mediterranean and Nordic-style diets, reported significant reduction in systolic and diastolic blood pressure, and also in inflammatory endothelial biomarkers. The same effect was also observed in mixed interventions and in CCTs with n-3 PUFAs supplementation. Dietary interventions with n-3 PUFAs contributes to improved endothelial and cardiovascular health in SM and associated risk factors.

RESUMEN El síndrome metabólico (SM) es un problema sanitario global. Los factores dietéticos, especialmente los ácidos grasos, pueden afectar la patología del SM. Sin embargo, las asociaciones entre los ácidos grasos poliinsaturados omega-3 (AGPI n-3) y el riesgo de SM pueden ser inconsistentes. Para aclarar esta relación entre AGPI n-3 dietarios y la función endotelial en el SM, realizamos una revisión sistemática. Se realizó una búsqueda bibliográfica en fuentes electrónicas de ensayos clínicos controlados (ECC) entre 2004 y 2020. Se incluyeron un total de 28 artículos en la revisión. Los estudios fueron analizados según intervención realizada: intervención dietaria (12 ECC), intervención con suplementación dietética (9 ECC) e intervenciones mixtas (7 ECC). Los estudios que utilizaron intervenciones dietéticas con aumento de AGPI n-3 a través de alimentos, como las dietas mediterráneas y nórdicas, reportaron una reducción significativa de la presión arterial sistólica (PAS), diastólica (PAD) y de biomarcadores endoteliales inflamatorios. El mismo efecto se observó en intervenciones mixtas y ECC con suplementación de AGPI n-3. Las intervenciones dietéticas con AGPI n-3 contribuyen a mejorar la salud endotelial y cardiovascular y sus factores de riesgo asociados.

Polyunsaturated Fatty Acids Differentially Modulate Cell Proliferation and Endocannabinoid System in Two Human Cancer Lines.

BACKGROUND AND AIMS: Evidence suggests that quantity and quality of dietary polyunsaturated fatty acids (PUFAs) play a role in the development of cancer. However, the mechanisms involved in this interaction(s) are not clear. Endocannabinoids are lipid metabolites known to have growth modulatory actions. We studied the effect of supplementation with PUFAs ω-6 and ω-3 (essential fatty acids, EFAs), saturated and monounsaturated fatty acids (non-EFAs) on the growth of tumor cells and modifications in their endocannabinoid content. METHODS: Cell cultures of human glioblastoma (T98G) and breast cancer (MCF7) were supplemented with 50 or 100 mmol EFAs and non-EFAs for 72 h. Cell proliferation was then determined by MTT, anandamide (AEA) levels by HPLC, total fatty acids profiles by GLC, CB1 receptor expression by WB and FAAH activity by spectrophotometric method. RESULTS: Fatty acids profile reflected the incorporation of the lipids supplemented in each assay. Arachidonic acid (EFA ω-6) supplementation increased AEA levels and inhibited the growth of T98G, whereas palmitic acid (non-EFA) enhanced their proliferation. In breast cancer (MCF7) cells, eicosapentaenoic acid (EFA ω-3) reduced and oleic acid (non-EFA) enhanced their proliferation. CB1 expression was higher in T98G and no differences were observed in FAAH activity. CONCLUSIONS: The growth of tumor cells can be differentially modulated by fatty acids and, at least in part, can be attributed to their ability to act on the components of the endocannabinoid system.

Effects of soy oil on murine salivary tumorigenesis.

Dietary fat influences dimethylbenzanthracene (DMBA)-induced tumorigenesis of several organs, including the salivary glands. There is not enough evidence to suggest that soy oil could also affect growth of salivary tumors. The main purpose of this work therefore was to study the effects of dietary soy oil on macroscopic parameters of chemically induced murine salivary gland tumors. Eighty BALB/c male mice were assigned to four groups: soy oil (SO), corn oil (CO, control), fish oil (FO) and olein (O). Two weeks later, tumors were induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). At the 13th post-injection week, the animals were sacrificed. In vivo tumor diameter, gland volume (total resected mass), tumor volume (microscopically measured), tumor remission and tumor histopathology were analyzed. The initial in vivo tumor diameter, gland and tumor volume were significantly greater in soy oil than in fish oil group. 26.7% of animals on the soy oil diet showed tumor remission. Sarcomas were more often found in the SO group, carcinomas in FO and the mixed-type tumors both in SO and CO groups. This study shows that the soy oil treatment resulted in larger tumors, some of which later became undetectable. It is necessary to further investigate these divergent results.

Fatty acid profile of human saliva: a possible indicator of dietary fat intake.

OBJECTIVE: Since conventional food questionnaires are not precise in assessing the dietary fatty acids, the purpose of this study was to determine the relationship between the salivary fatty acid profile and the alimentary habits of two different groups in an attempt to develop a more reliable way to determine the lipidic intake. DESIGN: Twenty adults of both sexes, with mixed (M) or vegetarian (V) diets were studied. Data about the fat intake were obtained by means of a Food Frequency Questionnaire (FFQ) and the presence of the main salivary fatty acids was determined by gas chromatography. RESULTS: A greater salivary concentration of alpha-linolenic acid (18:3 n-3) (2.82) was found in V than in M subjects (1.65) (p = 0.001), whilst arachidonic acid (20:4 n-6) was lower in V (3.93) than in M (4.52) (p = 0.045). The same difference regarding arachidonic acid was observed in the dietary fatty acid intake, also showing a significant correlation between its dietary and salivary levels in vegetarian subjects. CONCLUSIONS: These results show that salivary arachidonic acid, relevant for their eicosanoid production related to the tumourigenesis process and cardiovascular diseases, is influenced by dietary fats.

Traditional Dietary Pattern Increases Risk of Prostate Cancer in Argentina: Results of a Multilevel Modeling and Bias Analysis from a Case-Control Study.

There is increasing evidence that dietary habits play a role in prostate cancer (PC) occurrence. Argentinean cancer risk studies require additional attention because of the singular dietary pattern of this population. A case-control study (147 PC cases, 300 controls) was conducted in Córdoba (Argentina) throughout 2008-2013. A principal component factor analysis was performed to identify dietary patterns. A mixed logistic regression model was applied, taking into account family history of cancer. Possible bias was evaluated by probabilistic bias analysis. Four dietary patterns were identified: Traditional (fatty red meats, offal, processed meat, starchy vegetables, added sugars and sweets, candies, fats, and vegetable oils), Prudent (nonstarchy vegetables, whole grains), Carbohydrate (sodas/juices and bakery products), and Cheese (cheeses). High adherence to the Traditional (OR 2.82, 95%CI: 1.569-5.099) and Carbohydrate Patterns (OR 2.14, 95%CI: 1.470-3.128) showed a promoting effect for PC, whereas the Prudent and Cheese Patterns were independent factors. PC occurrence was also associated with family history of PC. Bias adjusted ORs indicate that the validity of the present study is acceptable. High adherence to characteristic Argentinean dietary patterns was associated with increased PC risk. Our results incorporate original contributions to knowledge about scenarios in South American dietary patterns and PC occurrence.

Synergistic anti-tumor effects of melatonin and PUFAs from walnuts in a murine mammary adenocarcinoma model.

OBJECTIVE: The aim of this study was to determine the effects of some polyunsaturated fatty acids plus phytomelatonin from walnuts in the development of mammary gland adenocarcinoma. METHODS: BALB/c mice were fed a semisynthetic diet supplemented with either 6% walnut oil and 8% walnut flour containing phytomelatonin (walnut diet: WD); or 6% corn oil plus commercial melatonin (melatonin diet: MD), or the control group (CD), which received only 6% of corn oil. Membrane fatty acids of tumor cells (TCs) were analyzed by gas liquid chromatography, cyclooxygenase (COX) and lipoxygenase (LOX) derivatives, and plasma melatonin by high-performance liquid chromatography; apoptosis and tumor-infiltrating lymphocytes by flow cytometry. RESULTS: TCs from the MD and WD mice showed significant decreases in linoleic acid compared with the CD group (P < 0.05). Significantly lower levels of LOX-[13(S)-HODE] were found in TCs from the MD and WD group than in CD (P < 0.0001). COX-[12(S)-HHT] was lower and 12 LOX-[12(S)-HETE] was higher in TCs from the MD group than form the WD and CD arms (P < 0.05). Plasma melatonin, apoptosis, tumor infiltration, and survival time were significantly lower in CD mice than in MD and WD mice (P < 0.05). CONCLUSIONS: This study shows that melatonin, along with polyunsaturated fatty acids, exerts a selective inhibition of some COX and LOX activities and has a synergistic anti-tumor effect on a mammary gland adenocarcinoma model.