Quantitative significance of measuring trimethylselenonium in urine for assessing chronically high intakes of selenium in human subjects

The purpose of the present study was to investigate the effects of Se restriction on the excretion of Se in men who had consumed high levels of this element during their entire lives. With the use of stable isotopes of Se as selenite, the excretion of methylated Se in urine was investigated in Chinese men (n 10) who had habitual chronic high intakes of this element. The relationship between either urine Se or trimethylselenonium (TMSe) to the estimated long-term Se intake was not linear over the entire range of intake, which was also true for the infusion of labelled selenite. A non-linear relationship was also found between urine TMSe and urine Se both for TMSe arising from catabolism of endogenous body Se and that from infused selenite. The data suggest a close precursor-product relationship of urine Se and its TMSe component based on the nearly identical specific activities for these two selenocompounds. Although dimethylselenide in breath was not measured in the present study, combining urinary TMSe with this breath test may be more useful in the assessment of long-term Se status.     

Effect of chronic selenite supplementation on selenium excretion and organ accumulation in rats

We examined the effect of chronic selenite supplementation on whole body and selected organ selenium (Se) accumulation, urine excretion of total Se and trimethylselenonium ion, and Se balance in adult male rats. Animals were housed in metabolic cages and given either deionized water or water containing 4 micrograms of Se/mL as selenite for 30 d. Absorption of selenite was nearly complete, with only approximately 10% of ingested Se appearing in feces. There was a rapid rise in urinary Se that reached a plateau within a few days and accounted for 54 +/- 2% of the intake. Excretion of trimethylselenonium ion (TMSe) in urine increased rapidly, representing 35-40% of urinary Se in the supplemented animals compared with only 2% for the control group. In one experiment, rats were killed at 30 d and total carcass Se was measured using isotope dilution analysis. Supplemented rats had only a modest increase in whole body Se (94 +/- 4 micrograms Se vs. 66 +/- 3 in controls). Calculation of Se balance in the supplemented rats showed that approximately 35% of ingested Se could not be accounted for by urine plus fecal losses combined with the portion retained in the carcass. The results from this study demonstrate that under the condition of supplementation at 4 micrograms of Se/mL of drinking water, pathways other than urinary and fecal excretion may account for a substantial portion of Se loss.     

Metabolism and disposition of erythritol after oral administration to rats.

The metabolism and disposition of erythritol was studied using [14C]erythritol in rats. When [14C]erythritol was administered orally at a dose of 0.1 g/kg body wt to male rats, only 6% of the total radioactivity was excreted as expired 14CO2 and 88% was excreted in the urine within 24 h. The excreted metabolite in the urine consisted of a single component identified as intact [14C]erythritol. The excretion of 14CO2 and the incorporation ratios of radioactivity into tissues increased with the oral dosage. After rats were given an intravenous injection of [14C]erythritol, approximately 1% was excreted as 14CO2 and greater than 94% was excreted in the urine as intact [14C]erythritol. The excretion of 14CO2 within 24 h was increased to approximately 10% when [14C]erythritol was administered to rats that had been adapted to erythritol by feeding a diet containing 10% erythritol for 2 wk. When [14C]erythritol was incubated in vitro with the cecal contents from rats adapted to erythritol, greater than 20% was fermented to 14CO2 and 60% to short-chain fatty acids in 6 h. These results indicate that most orally administered erythritol was excreted in the urine without any degradation and that the remainder was transferred to the lower intestine and fermented by microbes.     

In vivo reduction of arsenate in mice and rabbits

In vivo reduction of AsV, has been studied in mice and rabbits by determination of arsenic metabolites in plasma and urine after administration of [⁷⁴As]arsenate. The amount of AsIII in bladder urine of mice 1 hr after administration (0.04 or 0.4 mg As/kg body wt) corresponded to 0.4–2.9% of the dose. AsIII was also detected in plasma 1 hr after administration. In rabbits, catheterized in the bladder for continuous collection of urine, about 10% of the administered arsenate (0.04 mg As/kg body wt) was reduced and excreted in form of AsIII during 4 hr after administration, corresponding to about 20% of the total arsenic excreted. Arsenic excreted during the first hour was mainly in form of unmetabolized AsV and some AsIII. Thereafter the excretion of both AsIII and dimethylarsinic acid increased. The results indicated that AsV has to be reduced to AsIII before being methylated.     

Labeling hen's egg with 74Se for use in human metabolic experiments

Experiments were conducted with laying hens to explore quantitative aspects of incorporation of 75Se ( radioselenium ) at various dosing levels and for different chemical forms of an orally administered tracer. Quantitative distribution of the incorporated isotope in egg white and egg yolk was strongly influenced by both the chemical form of the label and the dosing level. The ratio of egg yolk:egg white selenium decreased with increased level of administered dose of selenite. In addition, the rate of incorporation and the amount of selenium in whole egg were higher when [75Se]selenomethionine was given as compared to [75Se]selenite. Characterization of the chemical form of selenium in egg white and egg yolk labeled biologically by giving hens radioactive selenite or selenomethionine was performed by classification as: selenite, selenoprotein and fat-bound selenium. Studies were then undertaken to achieve intrinsic labeling of egg white and egg yolk with stable isotope 74Se for purposes of exploring selenium bioavailability in humans. Enrichments of 74Se in egg white and egg yolk of hens given high dose selenite (54.4 micrograms 74Se ) were 20- and 28-fold, whereas in egg white and egg yolk of hens given low dose (10.9 micrograms 74Se ) they were 4- and 10-fold the level of natural abundance, respectively. The stable isotope-labeling studies indicated that a 7-day sequential dosing protocol with 20-100 micrograms Se per dose permitted sufficient enrichment of egg white (only high dose) and of yolk with the stable isotope 74Se for use in human metabolic studies.     

Selenium-mercury interaction during intestinal absorption of 75Se compounds in chicks

The effects of inorganic (HgCl2) and organic (CH3HgCl) mercury on the intestinal absorption of Se compounds [Na2(75)SeO3, Na2(75)SeO4, L-[75Se]methionine ([75Se]Met)] were determined in 3-wk-old White Leghorn cockerels by the in vivo ligated duodenal loop procedure. The intraduodenal dose contained 0.05 microCi 75Se, 0.01 mM Se, 150 mM NaCl and 0-1.0 mM Hg. In the presence of 1 mM inorganic Hg in the intraduodenal dose, the absorption of the inorganic 75Se compounds was only about 65% of that in the control group, whereas only a slight inhibitory effect on [75Se]Met absorption was observed. Methylmercury had no effect on [75Se]selenite absorption. Precipitation of the 75Se-selenite in the intestinal lumen partly explained the direct interaction between inorganic Hg and Se compounds. Absorption of [75Se]Met and [75Se]selenite was also determined in chicks fed after hatching a purified diet supplemented with varying amounts of Hg (0-500 mg/kg) and Se (0-4 mg/kg). Dietary Hg significantly reduced the transfer of [75Se]selenite to body by enhancing the accumulation of the isotope in the intestinal tissue. Dietary Hg did not affect the absorption of [75Se]Met, but altered the whole-body distribution of this Se compound. Because interaction between Se and Hg was observed mainly between the inorganic compounds and with use of a manyfold excess of Hg over Se, the data suggest that intestinal interaction between these metals is not of great nutritional importance.     

Kinetics of a single administration of 74Se-selenite by oral and intravenous routes in adult humans

The purpose of this study was to explore the fate of a single dose of labeled selenium as determined by its route of administration. Thus, the appearance of a stable isotope of selenium, administered as 74-Se-selenite, was measured in plasma, urine, and feces, with neutron activation analysis, following a 81.7 micrograms dose of 74Se-selenite given either intravenously or orally in two groups (n = 4) of healthy, young adult men, who were otherwise maintained on a diet providing a constant and adequate selenium intake. From these isotopic data, measurable parameters of urine excretion, total body retention and selenite-exchangeable metabolic pool (Se-EMP) were defined to provide a quantitative assessment of selenium metabolism in these subjects. The initial 24-hr urine excretion of the label was higher for the intravenously administered label (18.2 +/- 2.1% of dose) compared to the oral dose (11.7 +/- 2.6% absorbed dose). Thereafter, the excretion of isotope was the same for both groups. For equivalent entry of Se into the body, measured total body retention and Se-EMP were the same for both groups. These initial kinetic data suggest that the overall utilization of selenium from a single administration of selenite is comparable for the two routes of intake and that the host's selenium requirement can probably be met adequately via the intravenous administration of selenite.     

Metabolic studies of [75Se]selenocystine and [75Se]selenomethionine in the rat.

1. The long-term fate in rats of an oral dose of [75Se]selenocystine was compared with that of an oral dose of [75Se]selenomethionine. 2. Urinary and faecal radioactivities were measured during the 1st week and whole-body radioactivity was determined for 10 weeks. Rats were killed at weekly intervals for 4 weeks and at weeks 6 and 10 for analysis of tissue distribution of 75Se. 3. Intestinal absorption of [75Se]selenocystine was 81% of the administered dose; that of [75Se]selenomethionine was 86%. Urinary excretion of absorbed [75Se]selenocystine was 13-9% and that of [75Se]selenomethionine was 5-8% in the 1st week. 4. Whole-body retention of 75Se was greater for [75Se]selenomethionine than for [75Se]selenocystine but after the 1st week it decreased at a similar rate in both groups. Tissue distribution of retained 75Se was also similar in both groups. 5. The initial utilization of [75Se]selenocystine was different from that of [75Se]selenomethionine. However, after the 1st week 75Se from both sources appeared to be metabolized similarly, suggesting that dietary Se of both forms is ultimately incorporated into the same metabolic pool. 6. When these findings were compared with those of earlier studies with [75Se]selenite and 75Se incorporated in vivo into rabbit kidney (RK-64Se) (Thomson, Stewart & Robinson, 1975) the metabolism of [75Se]selenocystine resembled that of [75Se]selenite and RK-75Se, rather than that of [75Se]selenomethionine.     

Absorption and retention of 75SeO3 in relation to soybean protein intake in the rat

The absorption and retention of ⁷⁵Se, given as an oral dose of ⁷⁵SeO₃, was studied in young male rats receiving different levels and sources of soy protein, with and without selenite and methionine supplementation. Rats fed a protein-free diet had a higher cumulative urine ⁷⁵Se excretion and a sligtly lower ⁷⁵Se absorption and ⁷⁵Se retention than rats fed diets containing 10% protein supplied as soya flour. Results indicated that supplementation with selenite decreased the fractional absorption and retention of selenium, but the overall effect was a marked increase in the total amount of selenium ingested, absorbed and retained. Methionine supplementation of a diet based on soya increased growth and PER: it also decreased slightly cumulative feces ⁷⁵Se excretion and increased ⁷⁵Se absorption, but only in rats fed diets supplemented with selenium. The present findings are consistent with the view that selenium homeostasis in the rat is maintained largely through changes in the urinary excretion of selenium and they show that an inadequate protein diet reduces the efficiency of retention of absorbed selenite.     

Conversion of dietary choline to trimethylamine and dimethylamine in rats: dose-response relationship

Trimethylamine (TMA) and dimethylamine (DMA) are normal components of human urine and are precursors of dimethylnitrosamine, a potent carcinogen. In part, DMA and TMA are products of the metabolism of dietary choline by intestinal bacteria. Most TMA formed in the intestinal tract is later oxidized and excreted as trimethylamine oxide (TMAO). Humans treated with large doses of choline smell "fishy" (the odor of TMA). Humans ingest choline as part of foods, and yet rarely smell fishy, suggesting that TMA formation must depend upon the dose of choline ingested. We found that, in adult rats, at low doses of choline (1.5 mmol/kg body wt) only 9 mumol choline (6% of the dose) reached the part of the intestine which is colonized by bacteria (the cecum and colon). After administration of 15 mmol choline/kg body wt, 237 mumol (16% of the dose) reached the cecum and colon. At both doses, 64-65% of the administered choline was absorbed from the intestine by 3 h after the dose. We found that orally administered choline slightly increased TMA and TMAO excretion at doses of choline smaller than 7 mmol/kg body wt, but that there was a disproportionately large increase in TMA excretion per 24 h when larger doses were administered (from 11 mumol TMA and 100 mumol TMAO per kg body wt in controls to 226 mumol TMA and 3617 mumol TMAO per kg body wt in rats treated with 15 mmol choline/kg body wt).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the magnitude of the selenite-exchangeable metabolic pool and whole body endogenous selenium in adult rats

The quantitative relationship between the size of the selenite-exchangeable metabolic pool (WSe-EMP) and whole body endogenous selenium (Seend) was investigated in adult male rats. Two experiments based on multiple labeling with stable isotopes were performed. One focused on short-term (7 d, Expt. 1) and the other on long-term (60 d, Expt. 2) relationships. Rats were fed a Torula yeast diet and water supplemented with [76Se]selenite at 0.1 micrograms Se/mL; the in vivo [74Se]selenite tracer was administered orally. Groups of three or four animals were killed at timed intervals and whole carcass or selected organs were analyzed for the stable isotopes 74Se, 77Se and 82Se with hydride generation/inductively coupled plasma mass spectrometry. The value of WSe-EMP was determined from plasma or urine isotope ratios. In Experiment 1, with plasma as the sampling compartment, WSe-EMP at 24 h was 36.5 +/- 1.2% of the baseline value of whole body endogenous selenium (Seend) and 36.3 +/- 1.8% at 7 d. When urine was the sampling compartment, the corresponding values were 3.9 +/- 0.3% and 43.1 +/- 2.8%, respectively. In Experiment 2, WSe-EMP (plasma) was 38.9 +/- 1.3% of Seend at 7 d, increasing to 45.5 +/- 1.6% at 60 d. The corresponding values for urine as the sampling compartment were 45.5 +/- 2.0% (7 d) and 61.5 +/- 1.7% (60 d), respectively.     

Comparative studies of selenium-75 (selenite and selenomethionine) absorption from various milk diets in suckling rats

Selenium (Se) absorption was studied in human milk, bovine milk and infant formula (Similac) using suckling rats as a model. The effect of age on Se absorption from the three milk diets extrinsically labeled with 75Se, either as selenite or selenomethionine, was also investigated. Milk diets were fed by gastric intubation and the radioactivity in the carcass, gastrointestinal tract and the liver were measured 3 h after feeding. There was no difference in [75Se]selenite absorption from the three milk diets between 8-20 d of age. However, significantly higher quantity of 75Se was absorbed from all three milk diets by 20-d-old rats than by the younger rats (46 vs. 32%). This increase in [75Se]selenite absorption with advancing age is opposite to what has been found for most other trace elements. When rats were fed milk diets labeled with [75Se]selenomethionine, the absorption of 75Se was approximately twofold higher in all age groups compared with 75Se absorption from selenite. No difference in [75Se]selenomethionine absorption existed among the three milk diets in 8- or 10-d-old suckling rats. However, at 15 d of age [75Se]selenomethionine absorption from human milk was higher (82%) than from either bovine milk (72%) or infant formula (72%). Between 8 and 20 d of age, absorption of [75Se]selenomethionine from the three milk diets decreased with advancing age. Adding sodium selenate to increase the total nonradioactive Se of human milk, bovine milk (endogenous plus the added selenium) did not affect the absorption of either [75Se]selenomethionine or [75Se]selenite.     

Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites

Results of kinetic and pharmacokinetic studies have suggested that dietary carnitine is not totally absorbed and is in part degraded in the gastrointestinal tract of humans. To determine the metabolic fate of dietary carnitine in humans, we administered orally a tracer dose of [methyl-3H]L-carnitine with a meal to subjects who had been adapted to a low-carnitine diet or a high-carnitine diet. Urinary and fecal excretion of radiolabeled carnitine and metabolites was monitored for 5 to 11 d following administration of the test dose. Total radioactive metabolites excreted ranged from 13 to 34% (low carnitine diet) and 27 to 46% (high carnitine diet) of the ingested tracer. Major metabolites found were [3H]trimethylamine N-oxide (8 to 39% of the administered dose; excreted primarily in urine) and [3H]gamma-butyrobetaine (0.09 to 8% of the administered dose; excreted primarily in feces). Urinary excretion of total carnitine was 42 to 95% (high carnitine diet) and 190 to 364% (low carnitine diet) of intake. These results indicate that oral carnitine is 54 to 87% bioavailable from normal Western diets; the percentage of intake absorbed is related to the quantity ingested.     

Selenium status of exclusively breast-fed infants as influenced by maternal organic or inorganic selenium supplementation

A longitudinal dietary Se supplementation study on lactating mothers was performed to determine the possibilities of improving the Se status of exclusively breast-fed infants. A total of 200 mothers randomized into three groups received either no Se supplements, 100 micrograms of selenite, or 100 micrograms of yeast-Se daily. Maternal and infant serum Se concentrations showed a linear correlation during exclusive breast-feeding. Yeast-Se in the dose administered was safe and more effective than selenite in increasing the Se concentrations of maternal serum and milk, and infant serum. The mean estimated daily Se intakes of the infants were 7.7 +/- 2.2, 8.9 +/- 2.2, and 11.5 +/- 4 micrograms, in the control, selenite, and yeast-Se groups respectively. Though the infant Se intakes of the unsupplemented and selenite-supplemented mothers were below the lower limit of the safe and adequate range as set by the US National Research Council, their serum Se concentrations increased steadily over the 6-mo study period. As maternal serum Se also increased by over 50% during the same period the results suggest that a maternal daily intake of 50-75 micrograms is adequate during lactation.     

Toxicokinetics and bioavailability of paraquat in rats following different routes of administration

The toxicokinetics and bioavailability of [14C]paraquat were examined in rats which had received a single dose (11.6 micrograms/kg) of the herbicide by the iv, intragastric, dermal or pulmonary route. In the pulmonary route studies, rats were exposed to an aqueous solution or liquid aerosols of [14C]paraquat through a tracheal cannula or [14C]paraquat aerosols in a nose-only inhalation chamber. After intratracheal, intragastric, and dermal administration of [14C]paraquat to the rat, the average bioavailabilities were 0.45 +/- 0.22, 0.12 +/- 0.03, and 0.038 +/- 0.027, which corresponded to 20.3 nmol, 5.4 nmol and 1.7 nmol of [14C]paraquat, respectively. Since the dose administered to the rat in the [14C]paraquat aerosol studies was unknown, the bioavailability for this exposure route could not be determined. However, about 27.5 nmol of [14C]paraquat was observed into the systemic circulation of the rat after inhaling [14C]paraquat aerosols through a tracheal cannula. [14C]paraquat administered to the rat iv was eliminated from the blood with a half-life of about 68 min. Urine and feces were the major excretion routes. The radioactivity absorbed into the systemic circulation of the rat was approximately equal to that excreted in the urine; about 23.8 nmol, 8.5 nmol and 1.5 nmol of [14C]paraquat were recovered from the urine of the rat after inhalation of [14C]paraquat aerosols in a nose-only exposure chamber, intragastric injection and dermal absorption of [14C]paraquat, respectively. Tissue distribution studies showed that the bulk of the [14C]paraquat administered to the rat by the inhalation and dermal routes remained at the sites of administration.     

Chemical stability of selenious acid in total parenteral nutrition solutions containing ascorbic acid

Reduction of selenious acid (H2SeO3) to elemental Se by ascorbic acid was investigated in regard to the stability of selenite in total parenteral nutrition (TPN) solutions. [75Se] H2SeO3 (100 micrograms Se/liter) was incubated at 25 degrees C with pure ascorbic acid (100 or 500 mg/liter) or added to complete TPN solutions containing similar levels of ascorbate. The mixtures were subjected to thin layer electrophoresis at pH 5.3 to separate HSeO3- from Se degree. In complete TPN formulas, little or no reduction of HSeO3- to Se degree occurred over a 24-hr period, whereas complete reduction occurred with pure ascorbic acid. Further experiments showed that the amino acid component of the TPN formula was preventing the reduction of selenite, and that reduction of selenite by ascorbate did not occur in buffered solutions having a pH of 5 or greater. These results show that reduction of selenite is strongly influenced by pH. At the concentrations of H2SeO3 and ascorbic acid commonly used, reduction to elemental Se is unlikely to be a practical problem in TPN solutions in the near-neutral pH range.     

Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats.

The intestinal absorption and in vivo kinetics of (6S)-[3H]-5-methyl-tetrahydrofolate (5-methyl-H4folate), (6S)-[3H]-5-formyl-H4folate and [3H]folic acid were investigated to determine whether inherent differences exist in the overall bioavailability of these folates in rats. Adult rats (n = 9 per group) were given an intragastric dose of the appropriate folate (50 pmol/100 g body wt) in 50 mmol/L ascorbate (pH 7). Each compound underwent nearly complete absorption within 8 h, and there was no significant difference in the excretion kinetics in relation to the form of folate administered. A biphasic pattern of excretion was observed over the following 8 d. Both urine and feces were important excretory routes. The rapid phase of total isotopic excretion (urinary and fecal) exhibited a half time (t1/2) of 0.11-0.12 d, whereas the t1/2 of the slower phase was 13.4-15.9 d. Isotopic distributions and the pattern of labeled folates in urine and tissues were similar regardless of the form administered. These results indicate that the bioavailability of orally administered folic acid, 5-methyl-H4folate and 5-formyl-H4folate is equivalent in rats under the conditions of this study.     

Fate of excess nicotinamide and nicotinic acid differs in rats

Rats administered excess nicotinamide and nicotinic acid were studied to determine the metabolic fate of pharmacological levels of these compounds. When a large amount of nicotinamide (500 mg/kg body wt) was intraperitoneally injected into rats, 32% of the dose was excreted as nicotinamide, 11% as N1-methylnicotinamide (MNA), 10% as nicotinuric acid, 5% as nicotinic acid, 3% as N1-methyl-4-pyridone-3-carboxamide (4-pyr) and 2% as N1-methyl-2-pyridone-5-carboxamide (2-pyr) during d 1 after the injection. Urinary excretion of these compounds gradually decreased with time and returned to normal by d 3. Urinary excretion of nicotinic acid and nicotinuric acid was observed only on d 1. When a large amount of nicotinic acid (500 mg/kg body wt) was intraperitoneally injected into rats, 55% of the dose was excreted as nicotinic acid and 15% as nicotinuric acid during d 1, and no excretion of these compounds was observed thereafter. The increase in excretion of nicotinamide, MNA, 2-pyr and 4-pyr was slight even on d 1. Excretion of nicotinic acid, nicotinuric acid, nicotinamide, MNA, 2-pyr and 4-pyr returned to normal levels on d 2. From these results, the different fates of excess nicotinamide and nicotinic acid are discussed.     

Relationship of membrane-bound sulfhydryl groups to vitamin D-stimulated uptake of [75Se]Selenite by the brush border membrane vesicles from chick duodenum

The uptake of selenite by purified brush border membrane vesicles isolated from duodena of rachitic or vitamin D-treated chicks was studied by using radioactive selenite and a rapid filtration technique. Cholecalciferol treatment (500 IU at 72 h) significantly enhanced selenite uptake, a response that decreased when the vesicles were stored at room temperature for 2.5 h prior to the uptake measurement. Preincubation of the vesicles in 1.0 mmol/L H2O2 reduced [75Se]selenite uptake, indicating the involvement of oxidizable groups in the uptake reaction. Iodoacetic acid (IAA), a sulfhydryl-blocking reagent, at 1-2 mmol/L concentration eliminated the difference in selenite uptake due to cholecalciferol and had no effect on vesicles from rachitic animals. A higher concentration of IAA (10 mmol/L) enhanced selenite uptake manyfold and increased the absolute difference due to cholecalciferol treatment. Single intravenous doses of 100 IU cholecalciferol, 100 IU ergocalciferol, or 0.1 micrograms 1,25-dihydroxycholecalciferol also stimulated selenite uptake, suggesting a general response to vitamin D compounds. Normal animals given a single dose of 1,25-dihydroxycholecalciferol 12 h prior to killing also responded. Treatments that enhanced the uptake of [75Se]selenite also increased the amount of membrane-bound sulfhydryl groups, suggesting the involvement of membrane-bound sulfhydryl groups in the vitamin D response. A significant increase in selenite uptake by intravenous 1,25-dihydroxycholecalciferol occurred within 10 min. This rapid effect provides a new tool to probe early biochemical effects of vitamin D on intestinal epithelium.     

Increase of urinary ketone body excretion in selenium-deficient rats is a ketone-specific change.

The effects of selenium (Se) deficiency on urinary ketone body excretion in starved rats were examined. Rats were fed a basal diet which was Se-deficient (Se content: 0.011 micrograms/g) or a Se-adequate diet (the basal diet supplemented with 0.1 micrograms Se/g as sodium selenite). On the 11th and 22nd week of the feeding period, Se-deficient status in rats fed the basal diet was verified by the observation that the Se content and glutathione peroxidase activity in their plasma, erythrocytes, and livers were markedly lowered. On the 4th, 6th, 11th, 15th, and 22nd week, the rats were starved for 48 h and the urinary excretion of ketone bodies (acetoacetate (AcAc) and 3-hydroxybutyrate (3-OHBA)), urea, and creatinine were examined. The urinary excretion of AcAc and 3-OHBA during the second 24 h of the 48-h starvation period were markedly higher in the Se-deficient rats than in the Se-adequate rats for all weeks examined, while the urine volume and the excretion of urea and creatinine were similar in the Se-deficient and Se-adequate rats, irrespective of the feeding period and the number of hours of starvation. On the 22nd week, the plasma ketone body levels were also determined and significantly higher plasma 3-OHBA levels were observed in the Se-deficient rats than in the Se-adequate rats 72 h after starvation began. These results indicate that Se deficiency causes an increase of urinary ketone body excretion in starved rats and that the increase is ketone-specific with no changes in major urinary profiles.