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Biomedical subjects

O A Levander

Publications and source records attributed to O A Levander.

At least 73 records · Page 4Linked to original sources

The effect of elevated selenium intake on colonic cellular growth in rats.

Both selenium and calorie restriction are anticarcinogenic in many tumor models, but the mechanisms of action are unknown. This study compared the effects of elevated selenium (Se) intake and calorie restriction on colonic cellular growth. Female weanling rats were divided into four groups: control, 40% calorie restricted, and 4 or 6 mg Se/l H2O as selenate. Control rats and rats given Se consumed the control diet ad libitum. Rats in the 40% calorie-restricted group were pair fed 40% less than the total intake of control rats with a diet designed to provide equal nutrients except calories from carbohydrate. After three weeks, rats were injected with [3H]thymidine (1 muCi/g body wt) and killed one hour later. Se at 4 and 6 mg/l H2O and 40% calorie restriction significantly decreased food intake, weight gain, colon weight, and total colon DNA compared with controls. Total number of cells per crypt was not affected by any treatment, whereas total DNA synthesis was significantly decreased, suggesting that the total number of colonic crypts are reduced by calorie restriction and Se treatment. The rate of cell division was decreased only in rats given 6 mg Se/l H2O. These results indicate that elevated Se intake and caloric restriction decrease colonic mucosal growth by decreasing growth in general, but only very high intakes of Se affect colonic cell turnover.

Animals↗

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.

Adult↗

Effect of various dietary factors on the deposition of selenium in the hair and nails of rats.

Noninvasive techniques to monitor selenium (Se) status at higher intake levels should be developed if Se supplements are to be given to human subjects as possible anti-cancer agents. Hair and nails have been suggested as indices of Se status because they are easily obtained, transported and stored. However, there has been little research on the potential influence of such factors as dietary Se intake or nutritional status on the levels of Se in hair and nails. Here we report the effects of chemical form of dietary Se and of methionine (Met) status on the Se content of rat hair and nails. Rats were fed diets containing 0.5, 1.5 or 2.5 micrograms/g of Se as sodium selenate (Na2SeO4) or L-selenomethionine (SeMet) for 8 wk. Hair and nail Se retention was two- to threefold greater when dietary SeMet was fed. Hair and nail Se levels increased as liver and muscle Se retention increased in rats fed SeMet, whereas in rats fed Na2SeO4, hair, nails and liver accumulated Se but muscle Se levels remained relatively unchanged. In a second experiment, rats were fed diets containing 0.1, 0.5 or 2.5 micrograms/g of Se as Na2SeO4 or SeMet, +/- added Met (0.3%) for 6 (+Met) or 7 (-Met) wk. Hair and nail Se retention was greater when Met was deficient than when this amino acid was not limiting. These results suggest that factors other than dietary Se intake affect hair and nail Se content and that these tissues should be used with caution for Se status assessment purposes.

Animals↗

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.

Animals↗

Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii.

Young female mice were fed torula-yeast-based diets deficient in vitamin E or selenium or supplemented with cod-liver oil to determine the effect of host antioxidant status on the therapeutic efficacy of the Chinese traditional antimalarial drug qinghaosu (QHS), a sesquiterpene endoperoxide. Vitamin E deficiency enhanced the antimalarial action of QHS against Plasmodium yoelii, both in terms of decreased parasitemia and improved survival but Se deficiency did not. A vitamin E-deficient diet containing 5% cod-liver oil had such strong antimalarial activity in itself that no additional therapeutic benefit of QHS could be demonstrated. Hematocrit values in parasitized mice treated with QHS or fed the cod-liver-oil-supplemented, vitamin E-deficient diet were normal. Nutritional manipulation of host antioxidant status may provide a promising prophylactic and/or therapeutic tool for the control of malaria.

Animals↗

Upper limit of selenium in infant formulas.

At present, the amount of selenium in infant formulas is not controlled and varies depending upon the selenium content of the raw materials used in its manufacture. Since selenium deficiency has been associated with two diseases of childhood, prudence dictates that the concentration of selenium in infant formula be standardized. Extrapolation from studies with human adults indicates that a daily intake of 10 microg of selenium is sufficient to meet the nutritional requirement of the infant while providing a reasonable margin of safety. Extrapolation from adult studies also suggests that intakes of 75-160 microg/d might have harmful effects in infants. On the other hand, no cases of selenosis in infants have been reported in high selenium areas of the United States, where human breast milk supplies as much as 47 microg/d. Therefore, it is proposed that infant formulas contain enough selenium to provide 10-45 microg/d.

Female↗

Human selenite metabolism: a kinetic model.

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.

Feces↗

Relative nutritional availability to rats of selenium in Finnish spring wheat (Triticum aestivum L.) fertilized or sprayed with sodium selenate and in an American winter bread wheat naturally high in Se.

A Finnish national programme to fertilize crops with sodium selenate led us to compare the nutritional availability to rats of selenium in two Finnish spring wheats (Triticum aestivum L.), either fertilized or sprayed with sodium selenate, with that in an American winter bread wheat naturally high in Se. Weanling male rats were given a Se-deficient Torula yeast diet for 4 weeks followed by either continued depletion or repletion for 4 weeks with graded levels of Se as sodium selenite (standard) or wheat (test food). Plasma and liver Se levels and plasma and liver glutathione peroxidase (EC 1.11.1.9; GSH-Px) activities were used as criteria of body Se status. The availability of Se under these conditions was calculated with the point-slope technique at two dietary levels of Se (Expt 1) and with the slope-ratio method (Expt 2). In the point-slope assay, the level of dietary Se fed had a considerable effect on the apparent availability values obtained which made interpretation of the results difficult. In the slope-ratio assay, no difference in the availability of Se from the various wheats was observed when plasma or liver Se levels were used as the response criteria. The Se in the fertilized wheat was somewhat more available than that in the sprayed wheat when plasma or liver GSH-Px activities were the response criteria. Overall, availability values (%) derived by averaging all four response criteria were 86, 77 and 73 for the fertilized and sprayed Finnish wheats and the American wheat respectively (sodium selenite 100). These results show that wheat is a relatively available source of Se to rats regardless of whether its Se content is naturally high or is increased by fertilization or spraying.

Animals↗

Dietary selenium intake and selenium concentrations of plasma, erythrocytes, and breast milk in pregnant and postpartum lactating and nonlactating women.

The selenium status of a group of 23 lactating and 13 nonlactating women was assessed from 37-wk gestation through 6-mo postpartum. The mean overall dietary Se intake of both groups of women was 80 +/- 37 micrograms/d. Plasma and erythrocyte Se levels were lower in the lactating than in the nonlactating mothers both before and after parturition. Breast-milk Se concentrations fell from 20 micrograms/L (0.25 mumol/L) at 1-mo postpartum to 15 micrograms/L (0.19 mumol/L) at 3- and 6-mo postpartum. A weak (r = 0.38) but statistically significant (p less than 0.025) relationship was observed between maternal plasma Se level and breast-milk Se concentration. The dietary Se intake of these lactating North American women appears sufficient to maintain satisfactory Se nutriture in their breast-fed infants during the first 6 mo of lactation.

Adult↗

Nutritional availability to rats of selenium in four seafoods: crab (Callinectes sapidus), oyster (Crassostrea virginica), shrimp (Penaeus duorarum) and Baltic herring (Clupea harengus).

1. The present study was conducted to determine the biological availability to rats of the selenium in four high-Se seafoods: crab (Callinectes sapidus), oyster (Crassostrea virginica), shrimp (Penaeus duorarum) and Baltic herring (Clupea harengus). 2. Weanling male rats were fed on a Se-deficient Torula yeast diet for 4 weeks followed by either continued depletion or repletion for 4 weeks with 0.05, 0.1 or 0.2 microgram Se as selenite/g, or 0.1 or 0.2 microgram Se as freeze-dried cooked test food/g. Plasma and liver Se levels or glutathione peroxidase (EC 1.11.1.9; GSH-Px) activities were used as indicators of body Se status. 3. Except for oysters, the biological availability of Se in all these seafoods was close to that of selenite (selenite 100%) when the criterion used was either plasma Se level or plasma GSH-Px activity. 4. By the criterion of increased liver Se level of restored hepatic GSH-Px activity, only herring-Se had a biological availability comparable to that of selenite-Se under all conditions tested, whereas crab-Se and oyster-Se were distinctly inferior in this regard. 5. Increasing the amount of crab-Se, oyster-Se or shrimp-Se supplied in the diet from 0.1 to 0.2 microgram/g changed the apparent availability (%) of Se for hepatic GSH-Px restoration from 38 to 78, 22 to 53 and 57 to 90 respectively. 6. The present study demonstrates that the availability of Se in certain foods is a function of the criterion chosen, the level of Se supplied in the diet, and possibly other unknown interacting dietary factors.

Animal Nutritional Physiological Phenomena↗

Effect of selenium deficiency on the chronic toxicity of adriamycin in rats.

The effect of selenium deficiency on the chronic toxicity of adriamycin was examined in rats fed diets adequate in vitamin E. Selenium-deficient and selenium-supplemented diets were fed to rats for 10 wk, after which groups of 10 rats fed each diet were given weekly intravenous injections of adriamycin in saline at doses of 0, 0.5 or 1.0 mg/kg body weight for 12 wk. All rats were killed at 24 wk. Even though the cardiac glutathione peroxidase activity in the selenium-deficient group was less than 1% of that of the selenium-supplemented group, the severity of the adriamycin-induced cardiomyopathy was similar in both groups. However, the selenium-deficient rats were more sensitive to the growth-inhibiting effect of the higher dose of adriamycin than the selenium-supplemented rats. Moreover, the lower dose of adriamycin caused a mild nephropathy in 70% of the deficient rats but affected only 10% of the supplemented rats. Selenium status may have to be considered when adriamycin is used as a chemotherapeutic agent.

Animals↗

Urinary excretion of selenium by New Zealand and North American human subjects on differing intakes.

Lower renal plasma clearances of selenium (CSe 0.1-0.2 ml min-1), indicating excretion of a smaller proportion of Se presented to the kidneys, were found in New Zealand (NZ) residents with low plasma Se ((Se)p 50-70 ng ml-1) on customary intakes below 30 micrograms d-1 Se. North American subjects consuming 80 micrograms d-1 with (Se)p 120-140 ng ml-1 had CSe between 0.2 and 0.3 ml min-1. Several weeks' supplementation with high-Se bread increased NZ subjects' (Se)p to 120-175 ng ml-1 and CSe to 0.4-0.7 ml min-1. (Se)p remained elevated when supplementation ceased, but CSe returned to the basal range within a few days. Americans' clearances showed no such abrupt decrease when their dietary intake was similarly reduced. The NZ residents thus appeared to excrete selenium more sparingly than others. Rapid alterations in clearance after supplements and single doses were probably due to changes in the proportions of different forms of selenium in the plasma.

Adaptation, Physiological↗

Considerations on the assessment of selenium status.

There is increasing interest in the techniques available for assessing Se status because of the accumulating evidence from laboratory animal experiments and human epidemiological studies that suggests a link between Se and the incidence of certain types of human cancer. In this paper, different methods of Se assessment are described, including analytical approaches (dietary intakes, tissue contents, and excreta levels), functional biochemical measurements (glutathione peroxidase activity), and functional physiological tests. The importance of considering interacting nutrients and other interacting substances is pointed out. Typical values of some Se status indicators reported in normal, deficient, and selenotic states are given.

Animals↗

Dietary selenium levels needed to maintain balance in North American adults consuming self-selected diets.

Dietary selenium intake and selenium balance were measured during 4 1-wk metabolic periods over the course of 12 months in 27 free-living adult volunteers consuming self-selected diets. Men consumed more selenium in their diets than women (90 +/- 4 versus 74 +/- 3 micrograms/day), but plasma selenium levels were similar for both sexes (136 +/- 4 versus 133 +/- 4 ng/ml, respectively). Neither dietary selenium intake nor plasma selenium levels varied seasonally. Regression of selenium balance versus intake indicated that adult men needed 80 micrograms SE/day to stay in balance, whereas women needed only 57 micrograms SE/day. When balance and intake were adjusted for body weight, the sex difference disappeared, and both men and women needed about 1 microgram of dietary selenium per kg of body weight per day to maintain balance. The levels of dietary selenium reported here as necessary to maintain balance in North American adults are considerably higher than those previously reported as needed for balance in adult women from New Zealand, a country where low selenium status is common. Our results indicate that the levels of dietary selenium needed to achieve balance are a function of lean body mass and historical selenium intake.

Adult↗