Postnatal selenium repletion protects lungs of neonatal rats from hyperoxia.

We reported previously that Se-adequate neonatal rat pups born to Se-adequate dams were resistant to lung damage by hyperoxia. To assess whether early postnatal Se repletion could also protect developing pups reared under hyperoxia, female Sprague-Dawley rats (n = 20) were bred and fed a Se-deficient (0.04 microgram/g) diet during pregnancy. On d 1 postpartum, dams were divided into two groups and fed either a Se-deficient diet or a Se-repleted (0.5 microgram/g) diet. On d 4 postpartum, litters in each group were randomly assigned to either air or high oxygen (greater than 95% O2) environments. Histologic evaluation of lungs from d-8 pups indicated that Se repletion significantly reduced the incidence of lung lesions caused by hyperoxia. Selenium-repleted pups also had significantly greater lung volumes and internal surface areas. The 7-d period of Se repletion resulted in significantly elevated maternal milk Se concentrations compared with a Se-deficient group, which was reflected in the pups by elevated plasma and hepatic Se concentrations and Se-dependent glutathione peroxidase (SeGPx) activities. Pulmonary glutathione concentration and SeGPx activity in pups were affected by oxygen exposure only, not by Se nutrition. Therefore, early postnatal Se repletion can protect the developing lung from oxygen-induced injury, a protection that is not entirely due to the effects of Se on pulmonary SeGPx activity and glutathione concentration.     

Carcass deposition of dietary long-chain odd carbon fatty acids by rats and their effect on plasma glucose and ketone bodies during starvation.

Weanling rats were fed diets containing various levels (0 to 40% of total dietary acids) of long chain, odd-carbon fatty acids (OCFA, 15:0 + 17:0) for 5 weeks. The OCFA did not significantly alter growth or feed efficiency and the OCFA were deposited in the carcass fat in proportion to their concentration in the diet fat. After the 5-week ingestion period, the rats were starved for 48 hours and the effect of carcass OCFA content on weight loss, fat loss, urinary total nitrogen, plasma glucose concentration and plasma ketone body concentrations was determined as a function of starvation time. The results demonstrate that OCFA catabolism during starvation results in a dose related increase in plasma glucose and dose related decrease in plasma ketone bodies without significantly altering the total weight loss, carcass fat loss, or urinary total nitrogen. Finally, the carcass percentage of OCFA did not change during starvation showing that these acids are as readily lost from the carcass during starvation as even chain fatty acids.     

Dietary selenium requirements based on glutathione peroxidase-1 activity and mRNA levels and other Se-dependent parameters are not increased by pregnancy and lactation in rats

The hierarchy of selenium (Se) requirements for growing rats ranges from <0.01 to 0.1 microg Se/g diet, depending on the choice of Se status parameter. To further evaluate the efficacy of molecular biology markers to determine Se requirements in later periods of the life cycle, which are less amenable to traditional approaches, we studied pregnant and lactating rats. Female weanling rats were fed a Se-deficient diet (<0.01 microg Se/g) or supplemented with graded levels of dietary Se (0-0.3 microg Se/g) for >10 wk, bred, and killed on d 1, 12, and 18 of pregnancy and d 7 and 18 of lactation; Se response curves were determined for 10 parameters including liver glutathione peroxidase (GPX). Growth, and mRNA levels for selenoprotein P, 5'-deiodinase, and GPX4 were not decreased by Se deficiency. GPX4 activity required 0.05 microg Se/g diet for maximum activity, similar to growing rats. Dietary Se requirements for plasma GPX3 activity decreased 33% in pregnancy, but returned during lactation to the requirement of growing rats. The Se requirement for GPX1 activity decreased 25% in pregnancy but not in lactation. GPX1 mRNA required 0.05 microg Se/g diet for maximum levels in both pregnancy and lactation, similar to growing rats. Clearly, Se requirements do not increase during pregnancy and lactation relative to Se requirements in growing rats. Unexpectedly, Se-adequate levels of GPX1 mRNA and activity declined to <40 and 50%, respectively, of nonpregnant Se-adequate levels during pregnancy and lactation, illustrating the need to fully understand biomarkers at all stages of the life cycle.     

Effect of selenium repletion on glutathione peroxidase protein level in rat liver

We have previously reported that liver glutathione peroxidase (GSH-Px, EC 1.11.1.9) protein level and activity decrease exponentially during Se deficiency. To determine the effect of Se repletion on these parameters, Se-deficient rats were repleted with 0.1 or 0.5 mg Se/kg diet as Na2SeO3 in a 30% torula yeast-based diet and were killed 0, 1, 2, 3, 5, 7 or 14 d later. GSH-Px protein was quantitated using anti-GSH-Px antibodies. Dietary repletion with 0.5 mg Se/kg diet increased GSH-Px protein and activity significantly (P less than 0.05) after 1 d. After 5 d for GSH-Px protein and 7 d for activity the rate of increase slowed, and at d 14 neither GSH-Px protein nor activity was significantly different from that of Se-adequate rats. Repletion with 0.1 mg Se/kg diet did not significantly increase GSH-Px protein or activity until 14 d. To examine the short-term effect of Se repletion, Se-deficient rats were injected intravenously with 15 or 60 micrograms Se as Na2SeO3 and killed 1, 3, 6, 12 or 24 h later. Only rats injected with 60 micrograms Se and killed 24 h later had a significant increase in GSH-Px activity along with a marginally significant increase in GSH-Px protein. These response curves indicate that homeostatic processes control the level of GSH-Px. The lack of an increase in GSH-Px until 24 h after Se administration implies that additional metabolic events after a rise in cellular Se may be necessary prior to an increase in GSH-Px synthesis in Se-deficient rats.     

Effect of intermittent supplementation with selenate on selenium status of rats fed selenium-deficient diet

To examine the selenium (Se) status of rats intermittently supplemented with Se, we measured tissue Se contents and glutathione peroxidase (GPx) activities in rats fed a Se-deficient diet intermittently supplemented with selenate. In experiment 1, four groups of male 4-wk-old Wistar rats were fed a Torula yeast-based Se-deficient diet (Se content, < 0.01 microg/g) for 28 d. During the experimental period, the diet of each group was supplemented with sodium selenate (0.17 microg Se/g) for 0, 1, 2 or 7 d/wk. The tissue Se contents and GPx activities both increased gradually with an increase in frequency of the selenate supplementation, and significant linear regressions were observed between the frequency and these Se indices. In particular, the correlation coefficient in the liver and plasma indices was nearly equal to a value of 1.0. In experiment 2, three groups of rats were fed the Se-deficient basal diet for 28 d. Among these, one group was daily supplemented with sodium selenate to the Se-deficient diet at a level of 0.17 microg Se/g, and another group was intermittently supplemented with the selenate at a level of 1.19 microg Se/g for 1 d/wk. The tissue Se contents and GPx activities both were increased by the selenate supplementation and no significant difference was observed between daily and weekly supplementation in the Se indices except in erythrocyte Se. These results indicate that Se status in the growth period is dependent on total Se intake in this period and that weekly intermittent supplementation with Se can maintain adequate Se status.     

Glutathione-dependent and ketone body-related enzymes in the selenium-deficient rat

Male rats, born of selenium (Se)-depleted dams and continuously fed a Se-deficient diet regimen or Se-repleted for 11 weeks, were used for some enzymatic determinations in samples from liver, heart, kidney and hind limb muscle. The Se-dependent GSH-Px activity in liver and kidney of the Se-deficient group was less than 0.5% of Se-repleted controls, whereas a 3-fold increase in liver and kidney GSH S-transferase activity was found in these Se-deficient rats. The Se-deficient group excreted 3 times more acetoacetate via the urine than their Se-repleted siblings. The activity of the key enzymes of ketone body utilization was similar in tissues from Se-repleted and Se-deficient rats. It is suggested that longlasting or even Se-unresponsive changes in enzymes of ketone body metabolism might have developed in these rats born of Se-depleted dams.     

Type I iodothyronine deiodinase activity after high selenium intake, and relations between selenium and iodine metabolism in rats.

Type I iodothyronine deiodinase (I-D), which catalyzes the production of the thyroid hormone 3,3',5-triiodothyronine from thyroxine, has recently been identified as a selenoenzyme. It is therefore of interest to investigate the relationships between selenium and iodine metabolism. In the livers of Se-deficient rats I-D activity was inhibited; the production of 3,3',5-triiodothyronine and 3,3'-diiodothyronine from added thyroxine was decreased by greater than 95% relative to Se-adequate controls. The hepatic I-D activity was also reduced in rats fed a diet with a low iodine concentration. Unaltered glutathione peroxidase activities in liver and plasma of these rats suggest, however, that with normal Se intake this metabolic pathway of Se is not affected by iodine depletion. When rats were administered 75Se-labeled selenium at levels equal to the amounts ingested from diets with Se concentrations of 0.3 or 2 mg Se/kg, greater Se concentrations were found in the thyroid and liver of the animals receiving the higher dosage. The thyroidal 3,3',5-triiodothyronine and thyroxine concentrations, however, were comparable in rats fed diets with 0.3 mg Se/kg diet as selenite and 2 mg Se/kg as selenite or L-selenomethionine. The measurement of the hepatic I-D and glutathione peroxidase activities in these animals showed that excessive Se supply does not elevate the activities of the two enzymes but might even have the opposite effect. At high Se intake tissue Se concentration cannot therefore be used as indicator of the selenoenzyme activities.     

Uncomplicated selenium deficiency produced in chicks fed a corn-soy-based diet

Day-old chicks were fed a practical-type diet based on corn- and soybean meal produced in a severely Se-deficient area of northeastern China. The diet contained 0.007 ppm Se and resulted in marked decreases in the activities of Se-dependent glutathione peroxidase in plasma and pancreas within 6 days of feeding. Chicks fed this basal diet showed histological signs of acinar atrophy of the pancreas, hyaline body formation, vacuolation and cytoplasmic shrinkage by 18 days and significantly elevated activities of amylase in plasma by 30 days. Each of these changes was prevented by supplementing the basal diet with Se to bring it to a level of 0.20 ppm. Chicks fed a Se-deficient purified diet based on crystalline amino acids also showed decreased Se-dependent glutathione peroxidase activities in plasma and pancreas, pancreatic damage as evidenced by histological examination and increases in plasma amylase activities. However, these signs of nutritionally induced pancreatic atrophy occurred sooner and were of greater magnitude than those observed in Se-deficient chicks fed the practical diet within the 30-day experimental period. These results, therefore, constitute the first report of nutritionally induced pancreatic atrophy in Se-deficient chicks fed a diet containing intact protein, and we suggest that a factor(s) associated with the practical diet acts to partially protect the chicks from this pathological consequence of severe Se deficiency.     

低硒对F344纯系大鼠子代神经行为发育和学习记忆能力的影响

目的建立F344纯系大鼠低硒动物模型,观察低硒对子代仔鼠神经行为发育和空间学习记忆能力的影响。方法以纯系F344大鼠为实验对象,采用人工半合成饲料(低硒组饲料硒含量<0.01mgkg,补硒对照组饲料中硒含量为0.1～0.3mgkg)建立低硒大鼠模型,观测子一代仔鼠哺乳期的生长体重变化、生长发育生理学指标和神经反射指标,并采用开场实验、Morris水迷宫实验检测其行为活动和空间学习记忆能力。结果(1)低硒组大鼠尾血GSHPx活性极其显著地低于对照组(P<0.001)。(2)低硒组仔鼠的出生体重和哺乳期神经发育不同时间点体重明显低于对照组。(3)仔鼠出生后第4天平面翻正和悬崖回避、第10天听觉惊愕反射实验中,低硒组评分均低于对照组(P<0.05),但在第7天平面翻正、悬崖回避和第11天后的听觉惊愕反射实验以及第12、14天前肢悬挂、后肢行走能力实验中,两组仔鼠结果差异无统计学意义(P>0.05)。(4)开场实验中:低硒组雄仔鼠在中央格停留时间、穿行格数较对照组明显减少(P<0.05)。(5)Morris水迷宫实验:①低硒组仔鼠第4、5天的定位航行实验中,平均潜伏期比对照组明显延长(P<0.05);在第6、9时间段的直线式搜索方式也较对照组减少(P<0.05);②低硒组在空间探索实验中,原站台象限活动时间较对照组减少(P<0.05)。结论成功利用纯系F344大鼠建立了低硒动物模型,母代长期硒缺乏导致了子一代F344仔鼠出生体重减低、生后体格发育和神经行为发育的迟缓,雄性仔鼠对新异环境中的适应能力减弱,并且导致了子代仔鼠空间学习和记忆能力能力的减弱。     

Selenium from selenium-rich Spirulina is less bioavailable than selenium from sodium selenite and selenomethionine in selenium-deficient rats

The bioavailabilty of selenium (Se) from selenium-rich Spirulina (SeSp) was assessed in Se-deficient rats by measuring tissue Se accumulation and glutathione peroxidase (GSH-Px) activity. For 42 d, rats were subjected to dietary Se depletion by consumption of a Torula yeast (TY)-based diet with no Se; controls were fed the same diet supplemented with 75 microg Se/kg diet as sodium selenite. Se-deficient rats were then repleted with Se (75 microg/kg) by the addition of sodium selenite, selenomethionine (SeMet) or SeSp to the TY basal diet. Selenium speciation in SeSp emphasized the quasi-absence of selenite (2% of total Se); organic Se comprised SeMet (approximately 18%), with the majority present in the form of two selenoproteins (20-30 kDa and 80 kDa). Gross absorption of Se from SeSp was significantly lower than from free SeMet and sodium selenite. SeMet was less effective than sodium selenite in restoring Se concentration in the liver but not in kidney. SeSp was always much less effective. Similarly, Se from SeSp was less effective than the other forms of Se in restoring GSH-Px activity, except in plasma and red blood cells where no differences were noted among the three sources. This was confirmed by measuring the bioavailability of Se by slope-ratio analysis using selenite as the reference form of Se. Although Se from SeSp did not replenish Se concentration and GSH-Px activity in most tissues to the same degree as the other forms of Se, we conclude that it is biologically useful and differently metabolized due to its chemical form.     

Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment.

This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin-induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se-deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin-induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation.     

Short-term dietary selenium restriction in young adults: quantitative studies with the stable isotope 74SeO3(2-)

A 45 d metabolic study was carried out in four young adult male North American residents consuming a controlled diet based on an amino acid mixture. During the initial 10 d, total daily selenium intake was adjusted to 107.7 (SE 0.1) microgram/d, which was reduced to 11.4 (SE 0.1) microgram/d for the remaining 35 d. Two doses of a stable isotope (74SeO3(2-)) were administered orally in the post-absorptive state on days 4 and 39 of the study. Se balance (faecal + urinary excretion) as well as stable isotope excretion studies were carried out for the entire 45 d period; blood plasma and erythrocyte Se concentrations were also monitored. Plasma Se concentrations (microgram/ml) fell progressively from the initial value of 0.132 (SE 0.007) to 0.083 (SE 0.008) at the end of the study. The erythrocyte concentrations of Se did not vary in a consistent manner (average value for the entire study 0.147 (SE 0.002) microgram/ml). Faecal excretion of unenriched Se decreased from 66 (SE 6) microgram/d for days 1-10 to 10.2 (SE 0.8) microgram/d for days 14-40. Mean urinary excretions of the unenriched Se were 43.9 (SE 2.8) microgram/d (days 1-10) and 26.9 (SE 4.6) microgram/d (days 14-40). Total balance (intake-faecal excretion-urinary excretion) for unenriched Se was (microgram/d):-18 (SE 7) days 10-19, -17 (SE 2) days 19-39, -5 (SE 1) days 38-45. Fractional absorption of the ingested label was 0.529 (SE 0.032) and 0.542 (SE 0.038) for the Se-adequate and Se-restricted phases of the study. However, urinary excretion of the absorbed label was reduced from 6.57 (SE 0.73)% for day 1 of the Se-adequate phase to only 3.32 (SE 0.26)% for day 1 of the Se-restricted phase. Similar observations were also made for day 7 of each phase. These findings indicate that immediate contribution of ingested Se to the urinary Se pool is small.     

Selenium deficiency and transsulfuration in the chick

Experiments were conducted to investigate the effect of selenium (Se) deficiency on the efficiency of cysteine formation from methionine (Met) in three strains of chickens. Hubbard, Leghorn, or crossbred (New Hampshire X Columbian) chicks were fed a crystalline amino acid diet that was fortified with both vitamin E and ethoxyquin but was essentially devoid of Se. The sulfur-containing amino acid (SAA) requirement was provided as equal quantities of Met and cystine (Cys-Cys) or as an isosulfurous level of Met alone. When fed diets unsupplemented with Se, all chicks exhibited depressed growth and markedly reduced blood glutathione peroxidase (SeGSH-Px) activities. SAA source had no effect on SeGSH-Px activity. Source of SAA also had no effect on growth rate of Leghorn or crossbred chicks, regardless of Se status. Se-deficient Hubbard chicks, on the other hand, gained faster and more efficiently when fed the Met-Cys-Cys combination than when fed an isosulfurous level of Met alone. Plasma concentrations of Cys-Cys and cystathionine were reduced in Se-deficient chicks of all strains. Homocystine was detected only in plasma of Hubbard chicks fed Se-adequate diets containing Met as the source of SAA. These findings support the view that transsulfuration efficiency may be impaired by Se deficiency in some strains of chickens.     

Bioavailability of selenium from raw and cooked ground beef assessed in selenium-deficient Fischer rats.

The literature on the bioavailability of selenium (Se) from meats, especially beef, is meager, and that which existed when this research began suggested that Se was not highly bioavailable. In addition, much of the analytical values for Se in beef predated the Food and Drug Administration's 1973 approval of Se as an additive to feeds and mineral premixes of livestock.

One hundred and thirty-six weanling female Fischer 344 rats were divided into two dietary groups: the selenium deficient group in which animals were fed a torula yeast (TY) basal diet which contained 0.008 mg/kg Se and the control group in which animals were fed the TY diet to which was added 0.10 mg/kg Se as sodium selenite.

After 6 weeks of dietary treatment liver glutathione peroxidase (GSHPx) activity had fallen in the Se-deficient rats to 2.4% of that of control rats. At this time (week 6) rats from the Se-deficient TY diet were refed diets containing 0.10 mg/kg Se as selenite, selenate, raw or cooked ground beef that had been freeze-dried. During the Se-repletion period rats were sacrificed at weeks 1, 3, 5 and 8. Liver GSHPx activity and total Se levels in liver and muscle tissue were the criteria of Se bioavailability. After 8 weeks of Se resupplementation the recovery of liver GSHPx activity compared to the control animals (set at 100%) were selenite (98%, p > 0.05), selenate (117%, p < 0.05), raw beef (127%, p < 0.05) and cooked ground beef (139%, p < 0.05). Total Se in both liver and muscle tissue reflected the liver GSHPx activity with the total Se concentration in tissues being highest for cooked beef.

The data suggest that bioavailability of Se from ground beef is greater than that from either selenite or selenate.     

Effects of dietary selenite, selenocystine and selenomethionine on selenocysteine lyase and glutathione peroxidase activities and on selenium levels in rat tissues

Weanling male rats were fed a basal selenium (Se)-deficient diet or this diet plus 2 ppm Se as either selenite, selenocystine (SeCys) or selenomethionine (SeMet) for 9 wk. The rats were killed by decapitation while anesthetized with ether, and tissues were assayed for glutathione peroxidase (GPx) and selenocysteine lyase activities, and for Se content. Dietary Se had no effect upon the activity of tissue selenocysteine lyase. This activity was highest in the liver, followed by kidney, muscle and testis in decreasing order. Although the GPx activity was lower in tissues of the Se-deficient rats, there were no significant differences in its activity between animals given the different chemical forms of dietary Se. Except for the kidney, the tissue Se concentrations were similar in rats fed selenite or SeCys, but the Se content in testis, muscle, pancreas, heart, spleen, whole blood, erythrocytes and plasma was significantly higher in rats fed SeMet than in those fed either selenite or SeCys. The greatest increase due to SeMet compared with the selenite and SeCys treatments was about 10-fold in the muscle compared with 1.3- to 3.6-fold for the other tissues.     

Trimethyllysine metabolism in lean and obese zucker rats during fasting

The effect of starvation upon the metabolism of trimethyllysine in lean and obese female Zucker rats was studied. All rats were fed a carnitine and trimethyllysine limiting diet for one to two weeks before starvation was initiated. Fed rats and rats starved for three, six, and nine days were used. Liver free and peptide-linked trimethyllysine, and urine total trimethyllysine were measured. Lean and obese Zucker rats had similar hepatic-free and peptide-linked trimethyllysine content when expressed per g protein or per mg DNA. Obese Zucker rats excreted more total trimethyllysine during starvation relative to lean rats. Starvation did not affect trimethyllysine excretion over time, although there were significant decreases in total carnitine excretion in both lean and obese starved rats. Both phenotypes demonstrated a high efficiency of entry of trimethyllysine into the carnitine biosynthetic pathway. We conclude that lean and obese female Zucker rats, similar to male Sprague-Dawley rats, are extremely efficient in the conversion of trimethyllysine into carnitine.     

肉碱对不全饥饿大鼠脂肪利用的影响

目的　探讨肉碱对不全饥饿大鼠脂肪利用的影响。方法　用限食的方法造成不全饥饿大鼠模型 ,在给予高脂饲料基础上观察对照组与给予肉碱的实验组血浆肉碱浓度、附睾脂肪垫重量、粪便中脂肪含量、尿酮体、糖原等指标的变化。结果　补充肉碱后 ,实验组动物血浆总肉碱浓度显著高于对照组 ( P<0 .0 0 1 ) ;附睾脂肪组织重量及粪便中脂肪含量均显著低于对照组 ( P<0 .0 5) ,而肝糖原和肌糖原含量显著高于对照组 ( P<0 .0 5) ;实验前期和中期实验组尿酮体排出减少 ,与对照组相比 P<0 .0 5。结论　补充肉碱对不全饥饿大鼠脂肪利用有一定的促进作用     

补硒对克山病病区粮饲养大鼠心肌线粒体单胺氧化酶活性的影响

90只断乳两周的Spragul-Dawley纯种大鼠,随机分为低硒、补硒及常备饲料三组,分别饲以克山病病区低硒粮(含Se 0.009ppm)、克山病病区低硒粮补亚硒酸钠(含Se 0.232ppm)及常备饲料(含Se 0.169ppm),观察硒对心肌线粒体单胺氧化酶活性(MAO)的影响,结果表明:与补硒和常备饲料组相比,低硒组心肌线粒体MAO活性明显下降。饲喂30,60,90天血浆硒含量和红细胞GSH-Px活性显著下降,补硒组心肌线粒体MAO和红细胞GSH-Px活性接近常备饲料组水平。     

Cephaloridine nephrotoxicity is potentiated by selenium deficiency but not copper deficiency in rats.

Lipid peroxidation may contribute to the nephrotoxicity of cephaloridine, a beta-lactam antibiotic. Copper and Se may protect against free radical damage, and dietary Se deficiency potentiates cephaloridine nephrotoxicity. The objectives of this study were to further investigate potentiation of cephaloridine toxicity by Se deficiency and to determine whether Cu deficiency increases cephaloridine-induced injury. Weanling male Sprague-Dawley rats were fed adequate, Cu-deficient, Se-deficient, and Se and Cu-deficient diets for 4 wk and subsequently injected i.p. with cephaloridine (1200 mg/kg body wt) or saline. Nephrotoxic response to cephaloridine occurred, with increased plasma urea, kidney weight, excretion of urinary enzymes, and kidney lesions. Cephaloridine also increased plasma sorbitol dehydrogenase activity. Selenium deficiency depressed kidney glutathione peroxidase activity (78%) and potentiated cephaloridine nephrotoxicity. Copper deficiency did not increase cephaloridine nephrotoxicity; the small depression (13%) in kidney Cu,Zn-superoxide dismutase activity may not have been sufficient to impair antioxidant status. However, the marked depression in kidney glutathione peroxidase activity during Se deficiency may have impaired antioxidant status and enhanced cephaloridine-induced injury. In contrast to results in the kidney, neither Se deficiency nor Cu deficiency potentiated cephaloridine hepatotoxicity, as assessed by plasma SDH activity.     

Effect of dietary methionine on utilization of tissue selenium from dietary selenomethionine for glutathione peroxidase in the rat

To study the effect of dietary methionine on the bioavailability of Se from selenomethionine ([Se]Met), weanling rats were first loaded with Se by feeding 0.5 mg Se as [Se]Met per kg diet of a low methionine (0.17% by analysis) torula yeast-based diet for 21 d, and then were fed an Se-deficient diet (less than 0.02 mg Se/kg) supplemented with 0, 0.4 or 0.9% methionine for 28 d. Plasma, liver and muscle Se increased 2.6-, 2.5- and 2.2-fold, respectively, during [Se]Met supplementation, and then the tissue Se declined exponentially during the Se-deficient diet period. Plasma, liver and muscle glutathione peroxidase (GSH-Px) activities decreased 43-50% during the [Se]Met supplementation period in spite of the increase in tissue Se. When these [Se]Met-loaded rats were fed the Se-deficient diet and supplemented with methionine, tissue GSH-Px activities increased significantly within 3 to 7 d, but then decreased for the remainder of the experiment. Calculation of the percentage of tissue Se present as Se in GSH-Px indicated that substantial Se from dietary [Se]Met was stored in tissues in a form different from GSH-Px when a low methionine diet was fed. These results indicate that the dietary methionine level can modulate the availability of Se from dietary [Se]Met and from stored tissue [Se]Met; the inability of stored [Se]Met to provide Se for GSH-Px synthesis over a prolonged period of time suggests that [Se]Met may not be an optimum form for Se supplementation.