Copper Concentrations In Kidney Research Articles

Effects of nickel chloride on reproduction of the rat and possible antagonistic role of selenium

Nickel (10–100 ppm added as NiCl 2) was studied to determine its effects on reproduction of Wistar rats. In nine experimental groups, females, males or both were exposed to nickel in drinking water. In one female group and one male group, the drinking water was also supplemented with 0.3 ppm selenium (added as Na 2SeO 3). Breeding success and the growth and viability of pups were recorded. Nickel, copper and zinc concentrations in kidneys, liver and skin (with fur) of the females, males and pups were determined with an atomic absorption spectrophotometer. In addition, histology of the male testes (from control and nickel-exposed groups) was studied. The female exposures started 14, 28 or 100 days before copulation and continued during pregnancy and lactation. When the males were exposed (for 28 or 42 days before copulation), NiCl 2 reduced both the number of pregnancies and the number of pups born. In the testes, NiCl 2 induced shrinkage of the seminiferous tubules, which seemed to close some of the tubules. In the tubules, NiCl 2 decreased the number of basal spermatogonia. When the females or both parents were exposed to NiCl 2, pup mortality during lactation was high. However, when the females were drinking NiCl 2 supplemented with selenium, all the pups survived and development of the total mass of the litters was even better than in the control group. In the same way, in males, selenium supplementation of the drinking water protected those pups that were born; but fertility was lower than with the control treatment. In the tissues studied, nickel accumulated most in the kidneys and then in the liver and skin. In each type of organ, there was a clear dose–response relationship. In the pups, in particular, selenium (given to the females) increased the amount of nickel in tissues compared with corresponding administration of nickel without selenium. In summary, selenium seemed to counteract the deleterious effects of NiCl 2 on the reproduction of rats.

Liver fibrosis in guinea pigs experimentally induced by combined copper and aflatoxin application

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administrated orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group liver damage was established. In the combined group liver injury was more frequent and more severe compared to the aflatoxin B1 group. Compared with the copper group biliary copper excretion was diminished and the kidney copper content was elevated in the Afl. B1 + Cu group. While copper concentrations in bile and kidney correlated with other parameters, notably the pathological lesions of the liver, no such correlation was found for liver copper. Therefore in this experiment the degree of Cu accumulation was not decisive for the liver lesions. The livers' capacity for excreting Cu by bile seems to be a much more important factor. Histologically only the livers of the combined group exhibited degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.

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.

Serum concentrations of zinc and copper in Bull Terriers with lethal acrodermatitis and tail-chasing behavior

Abstract Objective To establish similarities or differences in tissue concentrations of zinc, copper, and iron in Bull Terriers with lethal acrodermatitis (LAD) and tail-chasing behavior (TCB) and to confirm the suspicion that copper is involved in the etiopathogenesis of LAD. Samples Serum samples from 29 Bull Terriers (9 control dogs, 6 dogs with LAD, 14 dogs with TCB), and liver and kidney specimens from 2 dogs and 1 and 4 dogs with LAD or TCB, respectively. Procedure Serum, liver, and kidney mineral (zinc, copper, and iron) concentrations in Bull Terriers with LAD or TCB and in a group of control dogs were analyzed, using flame atomic absorption after wet ashing technique. Results Serum zinc and copper concentrations were lower (P < 0.05) in dogs with LAD, compared with values for control dogs and dogs with TCB. Liver zinc and copper concentrations were similar to serum values. Kidney zinc and copper concentrations were similar among the 3 groups. Serum, liver, and kidney iron concentrations had a wide range of variability within all 3 groups. Conclusion Copper deficiency is associated with LAD. The primary cause of LAD may be copper deficiency, with zinc involved secondarily, or combined zinc and copper deficiencies. The role of ion deficiency in TCB was not clarified. Clinical Relevance Serum zinc and copper concentrations should be determined when LAD is suspected. (Am J Vet Res 1997;58:808–810)

A molybdenum - sulfur - cadmium interaction in sheep

We determined the effects of increased dietary concentrations of molybdenum and sulfur on the accumulation and tissue concentrations of cadmium in sheep, and compared them with effects on copper. Forty sheep, each weighing approximately 40 kg, were adjusted for 3 weeks to a basal diet of 80% wheaten chaff and 20% lupin seed containing (per kg dry weight) 0·016 mg Cd, 0·45 mg Mo, 3·4 mg Cu, and 1·9 g S. On Day 0 of treatment, 8 sheep were killed and the tissues analysed for trace minerals to provide a baseline value. The remaining sheep were divided into 4 dietary treatment groups: control (basal diet plus 4 mg Cd/kg), +Mo (control diet plus 15 mg Mo/kg), +S (control diet plus 4 g S/kg), +Mo+S (control diet+15 mg Mo+4 g S/kg). The treatment period lasted 80 days, after which sheep were killed for tissue samples. Sulfur alone reduced the accumulation of Cd in liver, kidney, and muscle by 60% compared with control sheep (P < 0·05). Molybdenum alone reduced Cd accumulation by 40% in liver and muscle (P < 0·05) and 30% in kidney (P = 0·09). When provided together (+Mo+S), the effect was equivalent to feeding with Mo alone, showing that Mo blocked the effect of S. Cadmium concentrations in whole kidneys for the 4 respective treatments were 6·40 ± 0· 7, 2·8 ± 0·3, 4·5 ± 0·8, and 5·0 ± 0·5 mg/kg fresh weight. The pre-treatment concentration was 0·7 ± 0·2 mg/kg. For Cu in blood and tissues, the effects of Mo and S treatment were consistent with the thiomolybdate hypothesis, and were quite different from those seen for Cd. Copper concentrations in whole kidney for the 4 treatments were 4·1 ± 0·1, 3·5 ± 0·2, 4·7 ± 0·3, and 22·4 ± 3·9 mg/kg fresh weight. The pre-treatment concentration was 4·1 ± 0·3 mg/kg. The results show that increased dietary levels of Mo and S reduce the accumulation of Cd in tissues, and the mechanisms of action differ from those involving Cu.

Copper metabolism in analbuminaemic rats fed a high-copper diet

Copper metabolism in male Nagase analbuminaemic (NA) rats was compared with that in male Sprague Dawley (SD) rats fed purified diets containing either 5 or 100 mg Cu/kg diet. Dietary copper loading increased hepatic and kidney copper concentrations in both strains to the same extent, but baseline values were higher in the NA rats. There was no strain difference in true and apparent copper absorption nor in faecal endogenous and urinary copper excretion. NA rats had higher levels of radioactivity in kidneys at 2 hr after intraperitoneal administration of 64Cu. As based on the distribution of added 64Cu, about 70% of plasma copper appeared to be in the non-protein compartment in the NA rats, whereas in SD rats, it was only about 1%. It is concluded that the NA rats are able to maintain a relatively normal metabolism of copper, even after dietary copper challenge. In the NA rats, zinc concentrations in kidneys, liver and urinary zinc excretion were elevated when compared with SD rats. The high-copper diet did not affect tissue zinc concentrations and apparent zinc absorption in both strains of rats.

The combined effect of high iron and zinc intake on copper status in rats

The interactions between copper, zinc, and iron intake in rats were investigated with regard to copper status. Weanling male rats were fed purified diets containing two levels of each of the three elements in a 2(3) factorial design. The added amounts of copper, zinc, and iron in the diets were 5, 12, and 35 mg/kg feed or were 10 times as high. After feeding on the experimental diets for 4 wk, the rats were killed and copper concentrations in plasma and organs measured. Plasma copper concentration was lowered by high zinc and iron intakes but this was seen only in the rats fed the normal-copper instead of the high-copper diets. In essence, the effects of zinc and iron were additive. Neither in rats fed the normal-copper diets nor in those fed the high-copper diets did extra iron or zinc intake alter copper concentrations in liver, spleen, kidney, and tibia.

Quantitative immunohistochemical evaluation by image analysis of metallothionein in copper-loaded rat kidney.

Kidneys of copper-loaded rats were investigated immunohistochemically with a directly peroxidase-conjugated monoclonal antibody against metallothionein (MT). By means of an image analyzing system the area and the staining intensity of MT immunoreactivity in the proximal convoluted tubule (PCT) cells were determined. In the present study we compared the data obtained by image analysis with analytically determined tissue copper and MT concentrations of rats fed a high-copper diet (1 g/kg) for 16 weeks and sacrificed sequentially during this period. Our results provide evidence that the area of MT immunoreactivity correlates significantly with tissue copper and MT concentrations. Both the copper and MT concentrations in kidney rose to a maximum at 8 weeks and remained constant thereafter. The observed rise in the staining intensity of MT in PCT cells to a maximum at 6 weeks, which subsequently declined, suggests a continuing redistribution of copper and MT in the kidneys even after a maximum of concentration copper and MT is reached in the tissue.

Cisplatin-induced loss of kidney copper and nephrotoxicity is ameliorated by single dose diethyldithiocarbamate, but not mesna

Platinum, copper, and zinc concentrations in kidney and liver were monitored following administration of cis-diamminedichloroplatinum (Cisplatin, CDDP) alone or in combination with diethyldithiocarbamate (DDC) or mercaptoethanesulfonate (mesna). Compounds were administered in saline to F344 female rats as single bolus ip doses: 7.5 mg CDDP/kg body wt; 500 mg DDC/kg body wt 1 hr after CDDP; and 100 mg mesna/kg body wt 1 hr before CDDP, at the same time as CDDP, or 1 hr after CDDP. Tissues were collected at 4 hr, 1 day, 4 days, and 7 days post-CDDP dosing. CDDP alone produced significant increases in blood urea nitrogen (fourfold) and plasma creatinine (threefold) concentrations by Day 4. Concurrent with the toxicity, CDDP lowered kidney copper (−71%) by Day 4, but had little effect on liver copper except in copper-pretreated rats. Copperpretreated rats initially had a twofold higher kidney copper concentration and a fourfold higher liver copper concentration, but by Day 4, CDDP lowered copper concentrations in both organs to near the noncopper-treated levels. Platinum in kidney and liver rose 72–100% of peak levels within 4 hr post-CDDP and was relatively stable throughout the 7-day test period. Kidney zinc rose significantly by day 4 only in CDDP-treated rats. DDC protected against the kidney toxicity of CDDP and markedly changed kidney copper loss. Within 4 hr, DDC reduced kidney copper 60% while increasing kidney platinum to the highest concentration of any of the treatments. By Day 4, DDC-treated rats had ≈ 50% lower kidney platinum while copper returned toward control levels. A single dose of mesna did not significantly protect against CDDP nephrotoxicity and had little effect on kidney platinum, copper, or zinc. The patterns of copper loss and toxicity from CDDP alone or with DDC suggest that copper be further evaluated for its role in the mechanism of CDDP cytotoxicity.

Relationship of cadmium accumulation to zinc or copper concentration in horse liver and kidney

The concentrations of Cd, Zn, Cu, and metallothionein (MT) in the liver, renal cortex, and renal medulla were determined in 24 male and 15 female younger thoroughbreds (age 27 to 97 months) and two old male horses (age 154 months and 190 months). High correlations were found between Zn and MT in the liver (partial correlation coefficient 0.836), between Cd and MT in the renal cortex (partial correlation coefficient 0.786), and between Cd and Zn in the renal cortex (partial correlation coefficient 0.675), while the correlation between Cd and MT in the liver was low (partial correlation coefficient 0.124). In the renal medulla, high correlations were found between Cd and Zn (partial correlation coefficient -0.631), between Zn and Cu (partial correlation coefficient 0.881), and between Cd and Cu (partial correlation coefficient 0.785). Therefore, in the liver, the MT concentration is the most highly correlated with the Zn concentration and is not correlated with the CD concentration unless artificially exposed to Cd. In the renal cortex, the MT and Cd concentrations are very highly correlated with each other. The Zn concentration is about 20 micrograms/g when the Cd concentration in the renal cortex is the lowest.

Vitamin C Treatment in Menkes’ Disease: Failure to Affect Biochemical and Clinical Parameters

Menkes’ disease (kinky hair disease, McKusick 30940) is an X-linked recessive disorder characterized by progressive neurological degeneration, hypothermia, seizures, growth retardation, abnormal hair and abnormalities of the major arteries, with death usually within the first 3 years of life (Menkes et al., 1962; Danks et al., 1972). There is an abnormal distribution of copper with low serum, cerebrospinal fluid (CSF), brain and hepatic copper levels but increased copper concentration in kidney, muscle and gut. Cultured fibroblasts show an abnormal accumulation of copper but reduced levels of lysyl oxidase, a copper-containing enzyme (Royce et al., 1980). Decreased activities of other copper-dependent enzymes, such as cytochrome c oxidase, tyrosinase and dopamine-β-hydroxylase, explain many of the clinical symptoms. An abnormal metallothionein gene regulation in response to copper has been found (Leone et al., 1985), but the basic defect has yet to be identified.

Localization of bismuth radiotracer in rat kidney following exposure to bismuth

It has been proposed that alpha emitting 212Bi (t1/2 = 60 min) coupled to tumor-specific antibodies may be a useful radiotherapeutic agent. However, since Bi can accumulate in the kidney, it is necessary to characterize the factors influencing localization of Bi within this tissue in order to evaluate the potential for radiation damage to the renal system. In this study, the localization of Bi radiotracers was determined in kidneys of rats previously exposed and not exposed to mumole quantities of Bi. Following repeated injection of Bi (4 x 14 mumols (3 mg Bi)/kg bw) the element accumulated mainly in the kidney followed by liver, spleen, pancreas, bone, and brain. Kidney copper and liver zinc concentrations were higher in Bi-exposed rats than in non-exposed rats. Within the cytosol, in Bi-exposed rats, Bi radiotracer in the kidney was associated with a metallothionein-like protein (Mt). In contrast, non-exposed rats contained no detectable metallothionein-like proteins in the kidney and the Bi tracer was associated with the hemoglobin fraction of the cell. Thus, when Bi is administered in tracer quantities such as that incorporated for use as a radiopharmaceutical, no induction of, and association with, metallothionein-like proteins should occur. These results suggest that the potential nephrotic effects of 212Bi will be influenced by the individual's previous exposure to Bi-containing drugs, or other metallothionein-inducing insults.

Changes in trace-element concentrations after intravenous injection of an essential trace-element preparation for parenteral use in rats

This experiment was carried out to investigate the effects of intravenous injection of an essential trace-element preparation (TE-5) on iron, zinc, copper and manganese concentrations, and blood biochemical and hematological parameters in rats. The rats were treated by intravenous injection of TE-5 for 7 days and the following results were obtained: 1) Neither a 0.04 nor a 0.4 ml/kg/day injection of TE-5 affected the iron, zinc, copper and manganese concentrations in tissues. 2) At a higher dose (1.2 ml/kg/day), iron concentrations in liver and spleen, zinc concentrations in liver, kidney, tibia and plasma, copper concentrations in heart, kidney and whole blood, and manganese concentrations in brain, heart, spleen, kidney, femoral muscle, tibia and whole blood increased. 3) At the highest does (4 ml/kg/day), all rats died and iron, zinc, copper and manganese concentrations in tissues increased remarkably. 4) With injections of TE-5 (0.04-1.2 ml/kg/day), hemoglobin, hematocrit, alkaline phosphatase activity and blood urea nitrogen decreased slightly. These results suggest that iron, zinc, copper and manganese concentrations, and blood biochemical and hematological parameters are maintained at doses up to 0.4 ml/kg/day of TE-5, but that doses higher than that destroy homeostasis.

Effects of total parenteral nutrition containing essential trace elements on their concentrations in rats.

Twenty-four rats were equally divided into 4 groups and maintained for 1 week as follows: Group A (normal control) with a synthetic normal diet and distilled water, group B with conventional total parenteral nutrition (TPN), i.e., TPN without essential trace elements (ETE), group C with TPN supplemented with a usual dose of ETE solution (TE-5), and group D with TPN supplemented with 3 times the usual dose of TE-5. Body weight, trace element concentrations in various tissues and certain blood biochemical parameters were determined in these rats. The results were as follows: 1) No significant differences in body weight were observed among the groups. 2) The iron concentrations in plasma and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases, but dose-dependent increases in the concentrations of iron were observed in liver, spleen and kidney (groups C and D). 3) The zinc concentrations in plasma, whole blood, brain, heart, kidney and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases dose-dependently (groups C and D). 4) The copper concentrations in plasma, whole blood, liver, spleen, kidney, testis and tibia decreased significantly in group B as compared with group A. The addition of TE-5 resulted in a tendency for these decreases to diminish (groups C and D). 5) The manganese concentrations of whole blood in group B decreased significantly as compared with group A. The addition of TE-5 caused the manganese concentrations of various tissues in groups C and D to increase significantly as compared with group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental changes of selected minerals in Zucker rats.

Effects of obesity and age on copper, iron, zinc, sodium, potassium, and protein were compared in liver, kidney, brain, and muscle of obese (fa/fa) and nonobese (non-fa/fa) male Zucker rats. Blood plasma cerulopasmin, copper, zinc, sodium, and potassium were also determined. Mean brain weight of fa/fa rats was less than that of non-fa/fa rats at 12 weeks of age; mean brain protein concentration was greater in fa/fa than in non-fa/fa at 5 and 12 weeks of age. At 18-19 days of age, mean sodium concentration (mg/g protein) in liver of fa/fa was less than that of non-fa/fa. At 5 weeks of age, mean copper concentration (microgram/g protein) in kidney was greater in fa/fa. Mean total copper, iron, zinc, sodium, and potassium in liver and kidney were greater in fa/fa than in non-fa/fa at 5 weeks because of the larger livers and kidneys of fa/fa. Mean concentrations of copper, zinc, sodium, and potassium per gram of brain protein were slightly (6-10%) less in fa/fa than in non-fa/fa at 5 weeks. By 12 weeks, mean concentrations of copper in liver, kidney, (tibialis) muscle, and blood plasma, ceruloplasmin in blood plasma, zinc in liver and muscle, iron in muscle, and sodium in liver were greater in fa/fa than in non-fa/fa. However, total amount of each mineral in muscle at 12 weeks was less in fa/fa than in non-fa/fa because of the smaller mean muscle weight of fa/fa. Mean concentrations of copper and zinc in brain and of iron in liver and brain were less in fa/fa than in non-fa/fa at 12 weeks. The major age-related changes in fa/fa that were not observed in non-fa/fa were large increases in liver and kidney copper between 5 and 12 weeks of age. It seems that the abnormal mineral metabolism is a consequence of the obesity, but the mechanisms are not identified.

Copper-binding protein in acute copper poisoning

This paper presents a suicide case of copper sulfate ingestion. Post-mortem autopsy revealed mucous membrane necrosis of the esophagus and the stomach. Histological examination revealed centrilobular necrosis in the liver and renal insufficiency. The quantitative determination of copper, zinc and cadmium in various tissues showed that the copper concentrations in blood, liver, kidney and lung were 3.5–24-fold higher than those of the normal level, whereas zinc and cadmium concentrations were within normal range. Chromatographical patterns on Sephadex G-75 showed that most of the accumulated copper in the liver and kidney was bound to metallothionein (MT), a low molecular weight protein with high metal binding capacity which plays a role in the detoxification of heavy metals, while no copper bound to MT was found in the lung. These results suggest that the formation of Cu-induced MT in the liver and kidney occurred at the early stage in fatal acute copper poisoning.

Effects of copper administration on fetal and neonatal mice.

The effects of copper administration to neonatal male mice on the copper concentrations and activities of copper-containing enzymes in cerebrum, liver, and kidney were studied. Intraperitoneal copper injections at 7 and 10 days of age increased the activities of superoxide dismutase and cytochrome oxidase in cerebrum and liver, and also increased the copper concentrations in cerebrum, liver, and kidney at 13 days of age. Maternal copper administration during the late-gestational period (from 13 days gestation to delivery) decreased the activities of both enzymes and increased the copper concentration in cerebrum. This increased level of copper remained by 13 days of age after birth. Liver showed similar changes to those in cerebrum, but the renal responses were less remarkable. Maternal copper administration from the late-gestational through lactational periods affected neonatal growth, decreased the activity of cytochrome oxidase, and increased the copper concentrations in all tissues examined. It is known that the copper concentration and copper-containing enzyme activity are low in cerebrum of mottled mice as well as of patients with Menkes' disease. These results suggested that the cytochrome oxidase activity in cerebrum was decreased by not only copper deficiency but also excess. The combination of prenatal copper supplementation by means of maternal copper administration during the late-gestational period and intraperitoneal copper injections after birth, while being careful not to overdose, is expected to be efficient for the copper supplementation to mottled mice.

Strain differences in kidney copper concentrations of male rats

The copper concentrations of the kidneys of male rats of six inbred (BN, F344, LEW, SHR, WAG/Cpb, and WAG/Rij) and one random-bred Wistar strain were determined.In inbred rats the mean concentration varied between strains and ranged from 7.10 μg/g for F 344 to 23.48 μg/g for WAG/Cpb. The calculated coefficient of genetic determination (g(2)) was 0.88. A remarkable discrepancy was found between the two WAG inbred strains; the WAG/Cpb had a 2.5 times higher kidney Cu concentration than the WAG/Rij.Kidney Cu concentrations of random-bred rats varied considerably; the coefficient of variation of the means was 28 and 34% in two samples taken with a 1-yr interval, respectively, indicating inhomogeneity within the population.The results indicate that the individual differences in kidney Cu concentration have a genetic basis.

Hypertension-induced alterations in copper and zinc metabolism in Dahl rats.

It has been suggested that one risk factor in the development of hypertension and vascular disease may be abnormal copper and zinc metabolism. In the current study we tested the hypothesis that hypertension itself may result in alterations in the metabolism of these essential elements. Dahl salt-sensitive rats were fed diets containing 0.4 or 8.0% NaCl for 32 days. At the conclusion of the study, blood pressure was significantly higher in the rats fed a high NaCl diet than in controls. Liver, kidney, and heart copper concentrations were significantly lower in the rats fed a high NaCl diet compared with controls, while plasma copper levels were higher. In contrast, tissue zinc levels were higher in the rats fed a high NaCl diet than in controls, while plasma zinc levels were lower. It is hypothesized that alterations in copper and zinc metabolism may be one factor underlying tissue damage in these animals.

PLACENTAL COPPER TRANSPORT IN THE BRINDLED MOUSE

The X-linked mouse mutant brindled is a model for Menkes syndrome. In young hemizygotes, reduced liver and brain copper concentrations are associated with neurologic dysfunction. In fetuses copper concentrations in placenta and kidney are higher in brindled than controls while those in liver and carcass are lower. To treat the copper deficiency in brindled young, heterozygotes were injected at 16 or 18 days gestation with copper, 6 mcg/g/dose, as cupric chloride, 18 and 6 hours before sacrifice. Placental, carcass, and hepatic copper concentrations in brindled fetuses increased (p>0.006). Injection of methylprednisolone, 5 mcg/g, 20 hours before the copper, to increase fetal hepatic copper storage through metallothionein induction, resulted only in further increase in the carcass copper concentrations. These data suggest: placental copper transport in brindled fetuses is impaired; hepatic copper binding capacity of control and brindled fetuses is limited and cannot be augmented by pretreatment with methylprednisolone; extra-hepatic copper binding may be increased with methylprednisolone, which implicates induction of extra-hepatic metallothionein in both groups of animals.