High fructose intake significantly reduces kidney copper concentrations in diabetic, islet transplanted rats.

Trace element status is known to be altered in the diabetic state, although the factors affecting trace element homeostasis in this condition are not well understood. The authors examined the effects of a high fructose diet (40% wt:wt) vs a control diet on the copper (Cu), zinc (Zn), and iron (Fe) concentrations in the kidney, plasma, and red blood cells of islet transplanted (TX) and sham-operated (SHAM) rats. Male, Wistar Furth rats made diabetic by streptozotocin injection (55 mg/kg, iv) were given an intraportal islet transplant (1000 islets); control animals were sham-injected, sham-operated (SHAM). Rats within TX and SHAM groups were assigned to either a high fructose diet (40% fructose, 25% cornstarch, FR) or a purified control diet (33% cornstarch, 33% dextrose, CNTL) containing identical amounts of mineral mixture for a period of 6 wk. Kidney Cu concentration was significantly elevated among hyperglycemic TX-CNTL rats (224+/-25 nmol/g wet wt), but was markedly reduced in hyperglycemic TX-FR rats (109+/-14 nmol/g) relative to normoglycemic controls. This occurred in spite of similar levels of glucose, insulin (fed and fasted), insulin secretory capacity, body weight, and food intake in the TX-CNTL and TX-FR groups. Among the subgroup of rats with normal glucose levels post-TX, kidney Cu levels normalized and were unaffected by dietary treatment (normoglycemic TX-CNTL = 60+/-5 nmol/g; normoglycemic TX-FR = 40+/-2 nmol/g). Kidney Cu concentrations also were unaffected by fructose feeding in SHAM animals (CNTL, 60+/-4 nmol/g and FR, 51+/-5 nmol/g). Kidney Zn and Fe concentrations were similar among the treatment groups. Plasma and red blood cell (RBC) Cu, Zn, and Fe concentrations were also similar among the groups. Since fructose feeding led to a substantial reduction of kidney Cu concentrations in the presence of hyperglycemia, the authors suggest that this model can be useful in examining effects of altered kidney Cu accumulation in the diabetic animal.

Copper status of young men consuming a low-copper diet.

A study was conducted in 11 young men to evaluate the effect of a low-copper diet on indexes of copper status and to define an amount of dietary copper at which adequate copper status could not be maintained. The young men were confined to a metabolic research unit for 90 d. The study was divided into three periods, with dietary copper as the only variable. Dietary copper was 0.66 mg/d for 24 d, 0.38 mg/d for 42 d, and 2.49 mg/d for 24 d. Plasma copper, ceruloplasmin activity, ceruloplasmin concentration, and erythrocyte superoxide dismutase (SOD) were measured at selected time points during each dietary copper period. Urine was collected throughout the study. Plasma copper, ceruloplasmin concentration and activity, and urinary copper declined significantly during the lowest dietary copper period. Plasma copper, ceruloplasmin concentration, and urinary copper increased in response to repletion. The average erythrocyte SOD concentration was lower during the depletion period than in the periods before or after depletion, but it did not decline significantly over time in the depletion period. The results suggest that these indexes are sensitive to copper depletion; that 0.38 mg Cu/d is not sufficient to maintain copper status in normal, healthy young men; and that the minimum dietary copper requirement is between 0.4 and 0.8 mg/d.

Influence of dietary folic acid on the developmental toxicity of methanol and the frequency of chromosomal breakage in the CD-1 mouse.

The proposed increased use of methanol (MeOH)-based fuels raises the concern for an increased risk for MeOH toxicity. MeOH, which is detoxified in part via a folate-dependent pathway, is known to be teratogenic in rodents. Previous observations have implicated maternal folate status as a critical modulator for the developmental toxicity of MeOH. The current study extends these findings, examining the effect of maternal dietary folate intake on fetal folate stores, as well as identifying a possible marker for the prediction of the developmental toxicity of MeOH. Virgin female CD-1 mice were assigned to diets containing either 400 (marginal) or 1200 (control) nmol folic acid (FA)/kg, and and 1% succinylsulfathiazole for 5 weeks prior to mating and throughout breeding and gestation. From gestation day (GD) 6 through 10 dams were given by gavage deionized, distilled water (dH2O) or MeOH at 2.5 g/kg body weight, twice daily. On GD 18, mice were weighed and killed and the liver, kidneys, and gravid uteri removed and weighed. Implantation sites, live and dead fetuses, and resorptions were counted; fetuses were weighed individually and examined for cleft palate and exencephaly. The marginal FA dietary treatment resulted in low maternal liver (50% reduction) and red cell folate (30% reduction) concentrations, as well as low fetal tissue folate concentrations (60 to 70% reduction) relative to the adequate FA dietary groups. Marginal FA treatment alone resulted in cleft palate in 13% of the litters; there were no litters affected with cleft palate in the adequate FA-control group. Marginal FA-MeOH treatment resulted in a further increase in the litters affected by cleft palate (72% of litters affected). The percent of litters affected by exencephaly was highest in the marginal FA-MeOH group. The frequency of micronuclei in maternal and fetal reticulocytes, a marker for chromosomal abnormalities, was not influenced by either the marginal FA diet or by MeOH treatment. These results show that marginal folate deficiency in pregnant dams significantly increases the teratogenicity of MeOH.

Influence of maternal folate status on the developmental toxicity of methanol in the CD-1 mouse.

Methanol, which is detoxified via a folic acid-dependent pathway, has been shown to be teratogenic in mice. Given recent observations that the level of dietary folic acid intake may be inversely related to the occurrence of select birth defects in humans, we tested the hypothesis that dietary folic acid intake would influence the developmental toxicity of methanol. Virgin female mice were fed one of three diets containing 400 (low), 600 (marginal), or 1,200 (adequate) nmol folic acid/kg diet for 5 weeks prior to and following mating. On gestation days (GD) 6-15, dams were administered by gavage either vehicle (distilled, deionized water) or methanol at 2.0 or 2.5 g/kg body weight, twice daily. On GD 18, mice were weighed and killed and the liver, kidneys, and gravid uteri removed and weighed. Implantation sites, live and dead fetuses, and resorptions were counted; fetuses were weighed individually and examined for cleft palate and exencephaly. One third of the fetuses in each litter were examined for skeletal morphology. Maternal liver folate concentrations were approximately 40-50% lower in the low dietary folic acid groups than in the marginal and adequate groups; methanol did not affect maternal liver folate concentration at term. Maternal net gestational weight gain was lowest at the lowest dietary folate level but was not affected by methanol. Gravid uterus weights were lowest in the low dietary folic acid groups exposed to the high methanol dose and the number of live fetuses per litter was lowest in the low folic acid groups. Fetal body weights were lowest in the low folic acid groups and significantly lower in the methanol groups relative to vehicle-treated animals. Fetal crown-rump lengths were shorter in the methanol-treated groups; this parameter was not affected by folic acid treatment. Both methanol and low dietary folic acid increased the incidence of cleft palate, with the highest number of affected litters in the low dietary folic acid group. These results support the concept that maternal folate status can modulate the developmental toxicity of methanol.

Effect of dietary restriction during lactation on cardiac output, organ blood flow and organ weights of rats.

Cardiac output, organ blood flow and organ weights were examined in rats assigned at d 0 of lactation to a control (C) group fed ad libitum or an acutely restricted (AR) group fed 50% of the intake of C dams. Dams in each group were assigned to subgroups for measurement of milk yield or cardiac output, blood flow and organ weights. At d 14 of lactation, cardiac output and blood flow were measured with radiolabeled microspheres and milk yield with the tritiated water method. In AR dams cardiac output was 55% of that of C dams, but cardiac output relative to body weight did not differ between groups. Mammary gland blood flow and weight were reduced in AR dams. The weight of the kidneys, gastrointestinal tract and liver of the AR dams was less than that of C dams; however, relative blood flow to these organs did not differ between groups. Milk yield was reduced by 58% in AR dams compared to C dams. We conclude that dietary restriction during lactation negatively affects absolute cardiac output, blood flow to the mammary glands and milk yield, and that the reduced milk yield is associated with the decrease in mammary gland weight and blood flow.