Impact of conjugated linoleic acid administered to rats prior and after carcinogenic agent on arachidonic and linoleic acid metabolites in serum and tumors (original) (raw)
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Biochimica et biophysica acta, 2014
Conjugated linoleic acid (CLA) is thought to exert anticarcinogenic, antiatherogenic, anti-inflammatory and weight loss effects. The impact on eicosanoid biosynthesis may be one of the mechanisms of its action. The aim of this study was to establish whether CLA mixture supplemented daily after administration of carcinogen (7, 12-dimethylbenz[a]anthracene, DMBA) influenced the concentration of linoleic and arachidonic acid metabolites: 13- or 9-hydroxyoctadecadienoic acids (13-, 9-HODE) and 15-, 12- or 5-hydroxyeicosatetraenoic acids (15-, 12- or 5-HETE) and prostaglandin E2 (PGE2) in rat serum and DMBA-induced tumours. The correlations between polyunsaturated fatty acids (PUFA) and HETE and HODE contents in serum were also investigated. Female Sprague-Dawley rats divided into three groups according to the diet (1% Bio-C.L.A., 2% Bio-C.L.A. and plant oil in the control group) were used in the study. On the 50th day of life some of the animals in every dietary group were administered ...
Carcinogenesis, 1999
Previous research suggested that conjugated linoleic acid (CLA) feeding during the period of pubescent mammary gland development in the rat resulted in diminished mammary epithelial branching which might account for the reduction in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the objectives of the present study was to investigate the modulation of TEB density by increasing levels of dietary CLA and to determine how this might affect the risk of methylnitrosourea-induced mammary carcinogenesis. The data show a graded and parallel reduction in TEB density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was observed when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the mammary gland. Since both CLA and linoleic acid are likely to share the same enzyme system for chain desaturation and elongation, it is possible that increased CLA intake may interfere with the further metabolism of linoleic acid. Fatty acid analysis of total lipid showed that CLA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5-2% CLA. There was no perturbation in tissue linoleic acid, however, linoleic acid metabolites (including 18:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA. Of particular interest was the significant drop in 20:4 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoid biosynthesis. Thus the CLA dose-response effect on arachidonic acid suppression corresponded closely with the CLA dose-response effect on cancer protection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA.
Lipids, 1988
The comparative effects of high-fat diets {20%, w/w} on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz{a}anthracene {DMBA}-induced rats were studied using diets containing 20% primrose oil {PO}, 20% menhaden oil {MO) or 20% corn oil {CO). Sprague-Dawley rats fed the PO or MO diet had 21% or 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically {i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid {GLA}. Arachidonic acid {AA} levels were significantly higher {p < 0.05) in PO-fed than in CO-or M(~fed rats. MO-fed rats had significantly higher levels of plasma palm/tic acid, while palmitoleic, eicosapentaenoie {EPA) and docosahexaenoic (DHA} acids were detected only in MO-fed rats. As expected, linoleic acid {LA} and AA levels were lower {p < 0.05) in the MOfed rats than in POor CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2-10 times higher than in mammary fat pads of control rats. The synthesis of PGEI and LTB4 was significantly {p < 0.05} higher in PO-fed rats than in CO-fed or MO-fed rats, although PGE values were significantly {p < 0.05} higher in CO-fed rats than in MO or PO groups. The synthesis of eicosanoids in both mammary fat pads and mammary carcinomas of MO-fed rats was lower {p < 0.05} than in tissues of rats fed either CO or PO diets due to less AA precursor being fed and/or to competition between n-6 and n-3 fatty acids for cyclooxygenase and lipoxygenase. The ratios of monc~ enoic to dienoic eicosanoids in both mammary fat pads and mammary carcinomas were higher in the PO group than in the MO or CO groups. These results suggest that inclusion of GLA {PO feeding} or EPA and DHA {MO feeding} in the diet may decrease malignancy by altering eicosanoid profiles.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 1995
The effects of pure gamma-linolenic acid (GLA; C18:3, n-6) and dihomo-gamma-linolenic acid (DGLA; C20:3, n-6) were investigated in 7,12-dimethylbenz(~)anthracene (DMBA) (10mg/rat)-induced mammary tumors in Sprague-Dawley rats. 0.15 g of GLA, DGLA, or corn oil (CO) were administered (two times per week) by oral intubation, for 12 weeks to rats maintained on a 5% (w/w) CO diet. Tumor incidence, tumor multiplicity, and percent of tumor-bearing rats were highest in the CO group. Tumor multiplicity was significantly reduced in the GLA group (p = 0.015). Feeding of GLA and DGLA resulted in significant alterations in levels of these fatty acids in phospholipids of mammary tissue, thymus, colon, liver, stomach, and ovary. These results suggest that GLA may have a small, but significant, inhibitory effect on the development of DMBA-induced mammary tumors in rats.
Nutrition and cancer, 2015
The aim of the present research was to examine the effect of conjugated linoleic acids (CLA) supplementation on the activity of enzymes that take part in the synthesis of arachidonic acid (AA) and also to investigate the relation between their activity and the neoplastic process. The enzyme activities were established indirectly, because their measure was the amount of AA formed in vitro, being developed from linoleic acid as determined in liver microsomes of Spraque-Dawley rats. In addition, the indices of Δ(6)-desaturase (D6D) and Δ(5)-desaturase (D5D) were determined. To this aim, the method of high per-formance liquid chromatography with UV/VIS detection was used. Between the examined groups, statistically significant differences were observed in the activities of enzymes as well as D6D. The carcinogenic agent applied (DMBA) was found to significantly increase the activity of the examined enzymes. Negative correlation was found between the activities of desaturases and CLA suppl...
Cancer research, 1992
On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation with 7,12-dimethylbenz(a)anthracene and 3 weeks before starting promotion with 12-O-tetradecanoylphorbol-13-acetate. An inverse correlation (r = -0.92) was observed between papilloma number and level of LA; however, there was little difference in tumor incidence. A relationship between diet and carcinoma incidence was also found. The fatty acid composition of epidermal phospholipids reflected the dietary LA levels. 12-O-Tetradecanoylphorbol-13-acetate-induced epidermal prostaglandin E2 levels generally decreased with increasing dietary LA. To determine whether this inverse correlation between dietary LA and tumor yield was due to species differences or organ-model differe...
Journal of Nutrition, 2000
We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the Apc Min/ϩ mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of ␣-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or ␥-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the ⌬6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of Apc Min/ϩ mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by ϳ50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P ϭ 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA-and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2016
We investigated how different doses of conjugated linoleic acids applied for various periods of time influence breast cancer risk and fatty acids profile in serum of rats treated or not with 7,12-dimethylbenz [a]anthracene (DMBA). We also search for interactions among parameters describing health conditions and cancer risk. Animals were divided into 18 groups with different diet modifications (vegetable oil, 1.0%, 2.0% additions of CLA) and different periods of supplementation. In groups treated with DMBA mammary adenocarcinomas appeared. Due to the complexity of experiment apart from statistical analysis a chemometric tool-Partial Least Square method was applied. Analysis of pairs of correlated parameters allowed to identify some regularities concerning the relationships between fatty acid profiles and clinical features of animals. Fatty acids profile was the result of prolonged exposure to high dose of CLA and DMBA administration. These two factors underlined the differences in fatty acids profiles among clusters of animals.
Inhibition of Carcinogenesis by Conjugated Linoleic Acid: Potential Mechanisms of Action
The Journal of Nutrition, 2002
Conjugated linoleic acid (CLA) is composed of positional and stereoisomers of octadecadienoate (18:2); it is found in foods derived from ruminants (beef and lamb as well as dairy products from these sources). When a mixture of isomers is fed to experimental animals, chemically induced tumorigenesis of mammary, skin and colon is reduced. Importantly, many isomers of CLA are readily metabolized to desaturated/elongated products as well as -oxidized products, suggesting that these metabolites may be important anticancer compounds. Mechanisms of inhibition of carcinogenesis may include reduction of cell proliferation, alterations in the components of the cell cycle and induction of apoptosis. In addition, CLA modulates markers of immunity and eicosanoid formation in numerous species as well as lipid metabolism and gene expression. It is likely that CLA exerts inhibitory properties in carcinogenesis via one or more of these pathways with some tissue specificity. This review will explore recent advances in putative mechanisms of reduction of carcinogenesis by CLA.
2010
Backround: Conjugated linoleic acids (CLA) are a group of positional and geometric isomers of linoleic acid with proven beneficial influence on health. They show e.g. anticarcinogenic, antiobesity, and antiatherogenic effect. Milk, dairy products and meat of poligastric animals are their most valuable dietary sources, with cis-9, trans-11 CLA (RArumenic acid) being the predominant isomer. Dietary supplements with CLA became very popular, mainly among the overweight and bodybuilders. The aim of this study was to examine the influence of the food supplements with conjugated linoleic acid on carcinogenesis in female Sprague-Dawley rats and evaluation of CLA and other fatty acids distribution in their bodies. Animals were divided into four groups depending on the diet supplementation (oil or Bio-C.L.A. (Pharma Nord Denmark) given intragastrically) and presence or absence of carcinogenic agent (7,12-dimethylbenz[a]antharcene). Animals were decapitated at 21st week of experiment and serum and microsomes were extracted.