Dietary fat and selenium effects on ex vivo prostaglandin production in rat colon, kidney, and blood

The effects were determined of dietary fat and selenium (Se) levels on prostaglandin (PG) production in rat blood, kidney, and colon mucosa. For 30 weeks, male Wistar-derived MRC rats were prefed diets containing low (6 g/367 kcal) or high (20 g/367 kcal) levels of fat with one of three Se supplements from sodium selenite: 0.0, 0.1, or 2.0 ppm Se. PG production was stopped by adding aspirin immediately following removal of the blood, kidney, and colon samples. Separate samples were allowed to incubate 10 or 60 minutes before blockage of PG production for determination of ex vivo PG production. Prostaglandin E2 (PGE2), thromboxane B2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay following separation on silicic acid columns. Basal levels of the three PGs were not influenced by diet. PGE2 production in the colon was highest in the group fed the high-fat diet that contained 2.0 ppm Se at 10 and 60 minutes, but PGE2 production in the blood and kidney were not altered by diet. Thromboxane B2 production in the rats' blood was higher in those prefed high-fat diets, but it was not influenced by dietary Se. Production of 6-keto-PGF1 alpha in the blood and thromboxane B2 and 6-keto-PGF1 alpha production by the kidney and colonic mucosa were not influenced by either dietary fat or Se.     

Comparative studies on the effects of semipurified and commercial diet on longevity and spontaneous and induced lesions in the Syrian golden hamster

Syrian golden hamsters were fed a semipurified or commercial diet from weaning throughout life. Bis(2‐oxopropyl)nitrosamine (BOP) was administered at 8 weeks of age (10 mg/kg body wt, sc). Longevity was improved by 26% and 36% increases in the mean life‐spans of male and female hamsters, respectively, fed the semipurified diets. Carcinogen treatment did not alter survival. The age‐adjusted occurrence rates of pancreatic ductular proliferation, carcinomas, adenomas, and common duct polyps were higher in hamsters fed commercial diet; this indicates an earlier onset of these BOP‐induced lesions in hamsters fed this diet. However, their overall incidences were generally similar when the two diet groups were compared. Acinar cell nodules were observed only in hamsters fed semipurified diets and were elevated in BOP‐treated females. The onset of pancreatic ductular proliferation and adenomas, bile duct proliferation, parathyroid hyperplasia, and common duct papillary hyperplasia was earlier in females than in male hamsters, especially in groups fed commercial ration. Generalized vascular calcification was observed at an elevated rate and reached a higher overall incidence in hamsters fed commercial ration. The age‐adjusted rate of amyloidosis was high in female hamsters and elevated in groups that consumed the commercial ration. In addition, colitis and islet cell hyperplasia occurred more often and earlier in hamsters fed commercial ration, but gallbladder stones occurred most in animals fed semipurified diet. This paper discusses the possible association between these and other observed lesions and survival.     

Comparative toxicity and tissue retention of selenium in methionine-deficient rats fed sodium selenate or L-selenomethionine

Selenium (Se) toxicity is known to be affected by level of intake of the mineral, but there are conflicting reports on the relative toxicities of the various chemical forms of Se. We monitored Se toxicity in rats fed Torula yeast-based diets containing 0.1, 0.5 or 2.5 micrograms Se/g of diet as either sodium selenate (Na2SeO4) or L-selenomethionine (SeMet). Half the diets were supplemented to contain adequate dietary methionine (Met). Weights were monitored weekly for 6 (Met-adequate) or 7 (Met-deficient) wk, at which time the rats were killed. There were no significant differences in final weight among Met-adequate rats, regardless of level or form of dietary Se. Methionine-deficient rats all gained significantly less weight than their Met-adequate counterparts. Selenosis was most severe in the Met-deficient rats fed 2.5 micrograms Se/g of diet as Na2SeO4, as indicated by significantly impaired weight gains. Nonetheless, Se retention in serum, heart, brain, bone, testes, colon, skin, lungs and pancreas was greater in rats fed SeMet than in those fed Na2SeO4, and Met deficiency further intensified this trend. The kidney was the only organ in which Se levels were markedly higher in the severely poisoned Met-deficient rats fed Na2SeO4. Further research is needed to determine whether elevated kidney Se levels are related to the greater toxicity observed in the Met-deficient rats fed Na2SeO4.     

Chronic toxicity and retention of dietary selenium fed to rats as D- or L-selenomethionine,selenite, or selenate

Groups of 8 male weanling Sprague-Dawley rats were fed for 6 weeks Torula yeast-based purified diets containing 2.5, 5.0, or 10.0 μg Se/g added as D-selenomethionine (D-SeMet), L-selenomethionine (L-SeMet), sodium selenite, or sodium selenate. All rats consuming diets containing 10.0 μg Se/g experienced severe growth depression and diet within 29 days, regardless of the form of Se fed, whereas rats fed 2.5 μg Se/g diet gave no evidence of depressed growth and survived the entire experimental period. Selenium fed as D-SeMet was retained in the tissues as strongly as L-SeMet. Skeletal muscle and heart Se concentrations were markedly greater when D- or L-SeMet were consumed than when selenite or selenate were consumed. Lesser differences due to the form of dietary Se fed were seen in the retention of Se in red blood cells, plasma, or liver. The increased deposition of Se in muscle tissues was not reflected by proportionate increases in either plasma or RBC Se, so monitoring plasma or whole blood Se may not indicate the degree of increased total Se body burden.     

Dietary fat and selenium effects on ex vivo prostaglandin production in rat colon,kidney, and blood

The effects were determined of dietary fat and selenium (Se) levels on prostaglandin (PG) production in rat blood, kidney, and colon mucosa. For 30 weeks, male Wistar‐derived MRC rats were prefed diets containing low (6 g/367 kcal) or high (20 g/367 kcal) levels of fat with one of three Se supplements from sodium selenite: 0.0, 0.1, or 2.0 ppm Se. PG production was stopped by adding aspirin immediately following removal of the blood, kidney, and colon samples. Separate samples were allowed to incubate 10 or 60 minutes before blockage of PG production for determination of ex vivo PG production. Prostaglandin E₂ (PGE₂), thromboxane B₂, and 6‐keto‐prostaglandin F_1α (6‐keto‐PGF_1α) were measured by radioimmunoassay following separation on silicic acid columns. Basal levels of the three PGs were not influenced by diet. PGE₂ production in the colon was highest in the group fed the high‐fat diet that contained 2.0 ppm Se at 10 and 60 minutes, but PGE₂ production in the blood and kidney were not altered by diet. Thromboxane B₂ production in the rats’ blood was higher in those prefed high‐fat diets, but it was not influenced by dietary Se. Production of 6‐keto‐PGF_1α in the blood and thromboxane B₂ and 6‐keto‐PGF_1α production by the kidney and colonic mucosa were not influenced by either dietary fat or Se.     

Comparative studies on the effects of semipurified and commercial diet on longevity and spontaneous and induced lesions in the Syrian golden hamster

Syrian golden hamsters were fed a semipurified or commercial diet from weaning throughout life. Bis(2-oxopropyl)nitrosamine (BOP) was administered at 8 weeks of age (10 mg/kg body wt, sc). Longevity was improved by 26% and 36% increases in the mean life-spans of male and female hamsters, respectively, fed the semipurified diets. Carcinogen treatment did not alter survival. The age-adjusted occurrence rates of pancreatic ductular proliferation, carcinomas, adenomas, and common duct polyps were higher in hamsters fed commercial diet; this indicates an earlier onset of these BOP-induced lesions in hamsters fed this diet. However, their overall incidences were generally similar when the two diet groups were compared. Acinar cell nodules were observed only in hamsters fed semipurified diets and were elevated in BOP-treated females. The onset of pancreatic ductular proliferation and adenomas, bile duct proliferation, parathyroid hyperplasia, and common duct papillary hyperplasia was earlier in females than in male hamsters, especially in groups fed commercial ration. Generalized vascular calcification was observed at an elevated rate and reached a higher overall incidence in hamsters fed commercial ration. The age-adjusted rate of amyloidosis was high in female hamsters and elevated in groups that consumed the commercial ration. In addition, colitis and islet cell hyperplasia occurred more often and earlier in hamsters fed commercial ration, but gallbladder stones occurred most in animals fed semipurified diet. This paper discusses the possible association between these and other observed lesions and survival.     

低硒大鼠对紫阳高硒小麦硒的相对生物利用率

本文用耗竭—补充—耗竭的设计,以克山病病区低硒粮饲料(含硒0.006ppm)喂养大鼠6周后,观察了补充紫阳高硒小麦(含硒1.175ppm)或亚硒酸钠,使饲料含硒分别为0.219和0.223ppm时,以及停止补硒后,大鼠组织和血液硒水平和谷胱甘肽过氧化物酶(GSH-px)活性的变化,并评估了紫阳高硒小麦的相对生物利用率。结果表明,以血浆、红细胞、肾、肝和心肌硒水平为指标时,高硒小麦硒的平均生物利用率(补硒2、4和6周时)与亚硒酸钠相似,其相对生物利用率分别为98％,104％,100％,96％和101％(亚硒酸钠为100％);而以心肌和红细胞GSH-Px活性为指标时,其生物利用率(90％和70％)低于亚硒酸钠。但在补硒的各时期,血液和各组织对高硒小麦硒的相对生物利用率不尽相同。此外,在停止补硒3周时,高硒小麦维持心、肝和红细胞硒水平以及心肌GSH-Px活性的作用优于亚硒酸钠。     

Growth, reproduction rates and mammary gland selenium concentration and glutathione-peroxidase activity of BALB/c female mice fed two dietary levels of selenium

This research was designed to determine the effect of various levels of dietary selenium on growth of BALB/c female mice. The selenium concentration and glutathione peroxidase (GSH-Px) activity in different developmental stages of the mammary gland was determined in the female mice fed 0.03 and 1.5 ppm Se. The development stages studied were: virgin (at 20 and 26 weeks of age), pregnant, lactating and involuted mammary gland. Also, the effect of the two levels of dietary selenium (0.03 and 1.5 ppm Se) on second generation reproductive rates were determined. There was no effect of dietary selenium (0.03, 0.20 or 2.00 ppm Se) on the growth rate of the mice except during pregnancy. The pregnant mice fed the 1.5 ppm Se diet had a greater growth rate than the mice fed the 0.03 ppm diet. Selenium levels in the mammary glands were higher in mice fed the 1.5 ppm Se diet than those fed the 0.03 p]pm Se diet. However, only in the mice with the highest growth rate, 10-week-old virgins, pregnant and lactating mice, was there an effect of dietary selenium on mammary gland GSH-Px activity. The reproductive rates for the second generation mice fed the two diets were similar to rates of mice fed stock diet. When both mating pairs (male and female) consumed the 0.03 ppm Se diet, the reproductive rates were lower than all other mating pairs. Thus, two conclusions can be made from these studies. First, as measured by growth and reproductive capabilities there were no signs of toxicity in mice fed the 1.5-2.0 ppm Se diet. Secondly, the differentiative states of the mammary gland influenced the selenium requirement for GSH-Px activity     

Analysis of Bioavailability and Induction of Glutathione Peroxidase by Dietary Nanoelemental,Organic and Inorganic Selenium

Dietary organic selenium (Se) is commonly utilized to increase formation of selenoproteins, including the major antioxidant protein, glutathione peroxidase (GPx). Inorganic Se salts, such as sodium selenite, are also incorporated into selenoproteins, and there is evidence that nanoelemental Se added to the diet may also be effective. We conducted two trials, the first investigated inorganic Se (selenite), organic Se (L-selenomethionine) and nanoelemental Se, in conventional mice. Their bioavailability and effectiveness to increase GPx activity were examined. The second trial focused on determining the mechanism by which dietary Se is incorporated into tissue, utilising both conventional and germ-free (GF) mice. Mice were fed a diet with minimal Se, 0.018 parts per million (ppm), and diets with Se supplementation, to achieve 0.07, 0.15, 0.3 and 1.7 ppm Se, for 5 weeks (first trial). Mass spectrometry, Western blotting and enzymatic assays were used to investigate bioavailability, protein levels and GPx activity in fresh frozen tissue (liver, ileum, plasma, muscle and feces) from the Se fed animals. Inorganic, organic and nanoelemental Se were all effectively incorporated into tissues. The high Se diet (1.7 ppm) resulted in the highest Se levels in all tissues and plasma, independent of the Se source. Interestingly, despite being ~11 to ~25 times less concentrated than the high Se, the lower Se diets (0.07; 0.15) resulted in comparably high Se levels in liver, ileum and plasma for all Se sources. GPx protein levels and enzyme activity were significantly increased by each diet, relative to control. We hypothesised that bacteria may be a vector for the conversion of nanoelemental Se, perhaps in exchange for S in sulphate metabolising bacteria. We therefore investigated Se incorporation from low sulphate diets and in GF mice. All forms of selenium were bioavailable and similarly significantly increased the antioxidant capability of GPx in the intestine and liver of GF mice and mice with sulphate free diets. Se from nanoelemental Se resulted in similar tissue levels to inorganic and organic sources in germ free mice. Thus, endogenous mechanisms, not dependent on bacteria, reduce nanoelemental Se to the metabolite selenide that is then converted to selenophosphate, synthesised to selenocysteine, and incorporated into selenoproteins. In particular, the similar efficacy of nanoelemental Se in comparison to organic Se in both trials is important in the view of the currently limited cheap sources of Se.     

Effect of selenite, vitamin E and N,N'-diphenyl-p-phenylenediamine on liver organic solvent-soluble lipofuscin pigments in mice

The present experiment was designed to investigate the effect of selenium (Se) supplementation, as sodium selenite, on organic solvent-soluble lipofuscin pigment (OLP) accumulation and glutathione peroxidase (GSH-Px) activity in the livers of mice fed varying levels of vitamin E or N,N'-diphenyl-p-phenylenediamine (DPPD). Four groups of 16 female, weanling mice each were fed either a vitamin E-deficient diet, a diet supplemented with 30 mg/kg or 300 mg/kg vitamin E (as RRR-alpha-tocopheryl acetate), or a diet supplemented with 30 mg/kg DPPD. Each diet contained 0.05 ppm Se. At 5 months of age, eight animals from each dietary group were supplemented with an additional 0.1 ppm Se, as sodium selenite, in their drinking water. The remaining animals were fed their original diets through the 9-month experimental period. Selenite supplementation resulted in a significant increase in OLP concentration and GSH-Px activity in the liver of mice fed vitamin E- or DPPD-supplemented diets. Normal levels of vitamin E and DPPD (30 mg/kg) were not sufficient to protect against the oxidative effects of selenite; however, 10 times the normal level of vitamin E (300 mg/kg) markedly suppressed this oxidative effect.     

Effect of dietary selenium deficiency on incidence and size of 1,2-dimethylhydrazine-induced colon tumors in rats

Torula yeast diets deficient (less than or equal to 0.02 ppm) in selenium (Se) and a control diet supplemented with sodium selenite (0.1 ppm Se), were fed to 52 male Sprague-Dawley rats per diet for 23 wk following weaning. 1,2-dimethylhydrazine (DMH) was administered (20 mg/kg body weight) in 20 weekly i.p. injections after 3 wk of feeding. After 23 wk, 67% of the rats fed the Se-deficient diet had intestinal adenocarcinomas versus 63% on the 0.1 ppm Se diets. Diet also had no effect on the number or size of tumors per tumor-bearing animal or on the location of the tumors within the colon. The effects of Se deficiency on the hematological variables of white blood cell count, hematocrit, serum urea nitrogen and cholesterol concentrations were examined. Serum urea nitrogen levels were lower in Se-deficient DMH-treated rats (9.6 +/- 0.7 vs. 13.7 +/- 0.9 mg/dl, P less than 0.01) and serum cholesterol was higher in Se-deficient DMH-treated animals (69.0 +/- 5.5 vs. 50.7 +/- 3.9 mg/dl, P less than 0.05). Body weights of the Se-depleted group were lower in the DMH-treated animals (P less than 0.01) although food consumption did not differ. Controls without DMH did not show differences due to Se status for any variable examined. Se deficiency appears to affect DMH toxicity but nutritional adequacy (0.1 ppm Se) does not inhibit tumor development. The results of this study do not support the belief that Se deficiency enhances colon carcinogenesis.     

Dietary supplementation with high-selenium soy protein reduces pulmonary metastasis of melanoma cells in mice

The effect of high-selenium (Se) soy protein on pulmonary metastasis of murine B16BL6 melanoma cells was investigated in male C57BL6 mice. Isolated soy proteins (ISP) from soybeans grown with and without Se foliar application during seed development were compared. Five diets were studied, a basal AIN-93G diet or a basal diet containing 10% low-Se ISP, 5% low-Se + 5% high-Se ISP, 10% high-Se ISP, or 10% low-Se ISP supplemented with Se equivalent to that of the 10% high-Se ISP diet. The Se concentrations of the 5 diets were 0.13, 0.13, 1.9, 3.6, and 3.0 microg/g, respectively. Mice were fed the diet for 2 wk before and 2 wk after an i.v. injection of 5 x 10(4) viable cells. At necropsy, the number and size of tumors that had developed in the lungs were determined. In the control group, 13/18 mice exhibited > or = 50 tumors. The numbers of mice with > or = 50 tumors were 8/18, 7/18, 3/18, and 6/17 in the ISP-fed groups, respectively. The differences between the 10% high-Se ISP group, the Se-supplemented 10% low-Se group, and the control were significant (P < 0.05). Dietary supplementation with 10% low-Se ISP significantly decreased the mean number of tumors per group and the tumor size compared with the control. A greater reduction in these variables occurred in mice fed the 10% high-Se ISP diet. The inhibition by the Se-supplemented 10% low-Se ISP diet was similar to that by the 10% high-Se ISP diet. The whole-blood Se concentration was inversely related to the tumor number (R = -0.87, P = 0.052), tumor cross-sectional area (R = -0.91, P < 0.05), and tumor volume (R = -0.93, P < 0.05). These findings suggest that Se is responsible for the greater antimetastatic effect of the high-Se ISP. We conclude that the high-Se soy protein has a greater inhibitory effect than the low-Se soy protein on pulmonary metastasis of melanoma cells in mice.     

Relative bioavailability of seleno-compounds in the lactating rat

Bioavailability of the organic forms of selenium (Se), selenomethionine (Se-methionine) and Se-yeast was determined relative to that of an inorganic form, selenite, in the lactating rat. A purified, casein-based diet without added Se was fed to nine groups of rats throughout pregnancy to produce a marginal Se deficiency. During lactation, groups (n = 8) were fed experimental diets containing either 0.1, 0.25 or 0.5 ppm Se as selenite, Se-methionine, or Se-yeast. On d 18 of lactation, tissue Se and glutathione peroxidase (GSH-Px) activities of dams and pups were determined. Based on slope-ratio analyses, the bioavailability of Se-methionine and Se-yeast was greater than that of selenite in both lactating dams and their nursing pups. The greater availability of organic Se to pup tissues may be a direct result of the greater concentration of Se in the milk of dams fed organic Se. A dietary level of 0.25 ppm Se as Se-methionine ensured maximal GSH-Px activity in both dam and pup tissues, but 0.5 ppm Se was necessary when selenite or Se-yeast was fed. These results indicate that, regardless of form, the National Research Council recommendation for growing rats of 0.1 ppm Se is not adequate to replete lactating dams and maintain maximal tissue GSH-Px in nursing pups.     

Selenised casein protects against AOM-induced colon tumors in Sprague Dawley rats

Selenium (Se) has been shown to be protective against cancers in animal models at concentrations exceeding those considered essential for normal nutritional requirements. Organic forms of Se provided as dairy proteins were obtained from cows fed diets supplemented with yeast Se. The casein extracted from milk was found to contain approximately half the Se of the Se-enriched milk. This casein was included in a semi-purified AIN rodent diet so as to provide 1 ppm Se and 25% protein and was compared with AIN diets containing no added Se (control, 0.05 ppm), 1 ppm and 4 ppm Se as selenised yeast (Sel-Plex) Their influence on colon tumor expression was examined in rats induced with azoxymethane, the diets being introduced post-induction. The selenised casein diet at this concentration was effective in reducing colon tumor incidence (by 29%) and burden (decreased 52%, P < 0.05) relative to the control in rats 26 wk post-induction. Selenised yeast, when added at similar (1 ppm) and increased Se concentration (4 ppm), did not influence significantly colon tumor expression. However, in a second study, with Se yeast providing Se at 1 ppm, 4 ppm, and 8 ppm throughout the experiment, a significant reduction in tumors was observed with 8 ppm Se (colon tumor incidence was 15% lower and colon tumor burden was 35% lower, P < 0.05). However this was associated with a significantly lower body weight in the rats (down 10.5%, P < 0.05) indicating a possible disturbance with normal energy intake or metabolism. The form in which Se is presented in the diet may influence significantly its bioavailability and/or anticancer potential at given concentrations within a safe range. The efficacy of selenised casein and indeed other potential dietary sources deserve further investigation with regard to their ability to prevent colon tumors at concentrations considered safe in the diet.     

Selenium influences growth via thyroid hormone status in broiler chickens

As there is a possibility that Se influences the growth of animals via thyroid hormone metabolism, the following three experiments were undertaken in order to determine the effects of dietary Se on growth, skeletal muscle protein turnover and thyroid hormone status in broiler chickens. Broiler chickens were raised on a Se-deficient diet until 12 d of age and then used for the experiments. In Experiment 1, twenty-eight birds were randomly assigned to four groups and fed purified diets with the following amounts of Se supplementation: 0.0, 0.1, 0.3 and 0.5 mg Se/kg diet. Dietary Se supplementation significantly increased plasma 3,5,3'-triiodothyronine (T3) concentration and improved growth, while plasma thyroxine (T4) concentration was decreased. In Experiment 2, twenty-eight birds were assigned to four groups and fed either a Se-deficient diet or a Se-supplemented diet (0.3 mg Se/kg diet) with or without the supplementation of iopanoic acid, a specific inhibitor of 5'-deiodinase (5 mg/kg diet). The growth was promoted and feed efficiency was improved by dietary Se supplementation as was also observed in Experiment 1. However, this effect of Se was halted by iopanoic acid supplementation. Hepatic 5'-deiodinase activity was elevated by Se and inhibited by iopanoic acid. In Experiment 3, birds were fed on the following diets to show that Se influences growth of birds via thyroid hormone metabolism: Se-deficient diet, Se-supplemented diets (0.1 and 0.3 mg/kg) and T3 supplemented diets (0.1 and 0.3 mg/kg diet). Lower dietary T3 supplementation (0.1 mg/kg diet) resulted in growth promotion similar to Se supplementation, while higher level of T3 caused growth depression. Furthermore, it was observed that the rate of skeletal muscle protein breakdown tended to be increased by Se similarly to the effect of T3. In conclusion, it was shown in the present study that Se deficiency depresses growth of broilers by inhibiting hepatic 5'-deiodinase activity which causes lower plasma T3 concentration.     

膳食蛋白质水平对硒利用的影响 Ⅰ、膳食蛋白质水平对大鼠血及组织中硒含量及谷胱甘肽过氧化物酶活力的影响

用低硒(0.03ppm)及高硒(0.30ppm)两类饲料喂养大鼠共三月,每类饲料蛋白质水平从5.3—13.4％,饲料基本成分为玉米和黄豆,实验结果发现,在不同硒水平下,饲料蛋白质水平对机体利用硒的影响大不相同。在低硒(0.03ppm)饲料下,低蛋白组动物血及血、心、肾及胰织组中的含硒量最高,饲养蛋白质水平愈高,各组织中硒含量则显著降低。及肝组织中的谷胱甘肽过氧化物酶活力有相同趋势。在高硒(0.30ppm)饲料组则无此种趋势,相反,蛋白质水平愈高,在肝脏中的贮存愈好。文中并讨论了在我国克山病区单纯补充硒的意义。     

Evidence for increased selenium requirement for the rat during pregnancy and lactation

Adequacy of the National Research Council (NRC) selenium (Se) requirement for growth (0.1 ppm Se) was assessed in reproducing Sprague-Dawley rats. Either a casein-based diet with no added Se or the same diet supplemented with selenite to contain 0.05, 0.1, or 0.2 ppm Se was fed during pregnancy and lactation and to nonreproducing controls. Only 0.05 ppm Se was necessary to maintain maximal red blood cell (RBC) and liver Se concentrations and glutathione peroxidase (GSH-Px) activities in controls, whereas 0.2 ppm Se was necessary to maintain comparable RBC Se during pregnancy and tissue Se and GSH-Px activities during lactation. On d 2 of lactation, no differences in pup tissue Se or GSH-Px activities could consistently be related to maternal Se intake. By d 18 of lactation, however, Se status of nursing pups reflected maternal Se intake. Pups of dams fed 0.2 ppm Se had tissue Se and GSH-PX activities significantly greater than those of all other pups. Milk Se content correlated significantly with maternal Se intake and plasma Se and with pup tissue Se and GSH-Px activities. These results indicate that during reproduction 0.1 ppm Se is not adequate to maintain maternal tissue Se or GSH-Px activities comparable to those of normal controls; 0.2 ppm dietary Se is more appropriate, resulting in maternal GSH-PX activities similar to those of controls fed 0.1 ppm Se and milk Se concentrations that result in greater pup tissue GSH-Px activities.     

High-dose supplemental selenite to male Syrian hamsters fed hypercholesterolaemic diets alters Ldlr, Abcg8 and Npc1l1 mRNA expression and lowers plasma cholesterol concentrations

The aim of the present study was to elucidate possible cholesterol-lowering mechanism(s) of high-dose supplemental Se in the form of selenite, a known hypocholesterolaemic agent. Male Syrian hamsters (four groups, ten per group) were fed semi-purified diets for 4 weeks containing 0.1 % cholesterol and 15 % saturated fat with selenite corresponding to varying levels of Se: (1) Se 0.15 parts per million (ppm), control diet; (2) Se 0.85 ppm; (3) Se 1.7 ppm; (4) Se 3.4 ppm. Lipids were measured in the bile, faeces, liver and plasma. The mRNA expression of several known regulators of cholesterol homeostasis (ATP-binding cassette transporters g5 (Abcg5) and g8 (Abcg8), 7-hydroxylase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, LDL receptor (LdLr) and Nieman-Pick C1-like 1 protein (Npc1l1)) were measured in the liver and/or jejunum. Oxysterols including 24-(S)-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol (27-OHC) were measured in the liver. Significantly lower total plasma cholesterol concentrations were observed in hamsters consuming the low (0.85 ppm) and high (3.4 ppm) Se doses. The two highest doses of Se resulted in decreased plasma LDL-cholesterol concentrations and increased mRNA levels of hepatic Abcg8, Ldlr and jejunal Ldlr. Higher hepatic 27-OHC and TAG concentrations and lower levels of jejunal Npc1l1 mRNA expression were noted in the 1.7 and 3.4 ppm Se-treated hamsters. Overall, Se-induced tissue changes in mRNA expression including increased hepatic Abcg8 and Ldlr, increased jejunal Ldlr and decreased jejunal Npc1l1, provide further elucidation regarding the hypocholesterolaemic mechanisms of action of Se in the form of selenite.     

The effect of dietary fat on metastasis of the Lewis lung carcinoma and the BALB/c mammary carcinoma

The effect of feeding mice diets high in beef tallow (high in saturated fat) or corn oil (high in polyunsaturated fat) on the production of lung metastases by the Lewis lung carcinoma and the BALB/c mammary tumor was determined. Diets were fed ad libitum, and the mice fed the high-fat (24.6%) diets consumed more calories and gained more weight than those fed the control (5%) diets. With the Lewis lung carcinoma, we found that both high-fat diets significantly increased the growth of the primary tumor in the footpad as well as the number of spontaneous metastases produced after the primary was removed; this was in comparison with results from the appropriate control diets. With the BALB/c mammary tumor, the high-fat beef tallow diet (but not the corn oil diet) significantly increased the number of lung metastases formed after tail vein injection. In addition, the group given the control corn oil diet had more metastases than the group given the control beef tallow diet. Overall, these studies showed that the consumption of high-fat/high-calorie diets increased metastasis compared to the consumption of high-fat/high-calorie diets increased metastasis compared to the consumption of low-fat diets. However, the results varied depending on the tumor model used and the type of fat.     

Effect of dietary benzylselenocyanate on azoxymethane-induced colon carcinogenesis in male F344 rats.

The effect of dietary benzylselenocyanate (BSC) and its analogue, benzylthiocyanate (BTC), and sodium selenite during the initiation and postinitiation phases of azoxymethane (AOM)-induced intestinal carcinogenesis was studied in male F344 rats. Animals intended for initiation study were fed the high-fat (23.5% corn oil) diets containing 25, 50, and 100 ppm BSC (10, 20, and 40 ppm selenium, respectively) and 100 ppm BTC and 4 ppm selenium (as sodium selenite in drinking water); those intended for postinitiation study were fed the high-fat control diet. Two weeks later, all animals were injected subcutaneously with AOM (15 mg/kg body wt) once weekly for two weeks. Three days after the last AOM injection, animals in the initiation and postinitiation studies were transferred respectively to the high-fat diet and high-fat diets containing BSC and BTC and sodium selenite in drinking water. This regimen was continued until 36 weeks post-AOM injection. BSC inhibited the small intestinal and colon adenocarcinoma incidence and multiplicity of colon adenocarcinomas when fed during the postinitiation phase. Sodium selenite inhibited the incidence and multiplicity of colon adenocarcinomas only during the postinitiation phase. BTC had no inhibitory effect when fed during the initiation and postinitiation phases. The colonic mucosal ornithine decarboxylase activity was significantly inhibited by the administration of all three compounds, BSC (78%), BTC (62%), and sodium selenite (44%). It is concluded that the BSC has an inhibitory effect on the intestinal carcinogenesis in animals fed the high-fat diet.