Effect of acute administration of mercuric chloride on the disposition of copper, zinc, and iron in the rat

The present study was designed to investigate the effect of mercuric chloride administration on copper, zinc, and iron concentrations in the liver, kidney, lung, heart, spleen, and muscle of rats. The results showed that after dose and time exposure to mercuric chloride, the concentration of mercury in the six tissues was significantly elevated. Data showed that there were no interaction between mercury and tissue iron. There was a considerable elevation of the content of copper in the kidney and liver. The most significant changes in the copper concentration took place in the kidneys. About a twofold increase in the copper content of the kidney was noted after exposure to mercuric chloride (3 mg and 5 mg/kg). Only slight elevations in the copper content occurred in the liver, especially in high dose and longer exposure time. In the remaining organs, the copper content was not changed significantly (p>0.05). The most significant changes in the zinc concentration took place in liver, kidney, lung, and heart (5 mg/kg). Marked changes in kidney zinc concentrations were observed at any of the specified doses. Zinc concentrations were significantly increased in kidney of rats sacrificed 9–48 h after sc injection of HgCl₂ (5 mg/kg); in liver obtained from rats at 18, 24, or 48 h after injection; and in lung after 24 or 48 h of treatment. The heart and spleen zinc concentrations were elevated at 24 and 48 h after injection of HgCl₂ (5 mg/kg), respectively. The results of this study implicate that effects on copper and zinc concentrations of the target tissues of mercury may play an important role in the pathogenesis of acute mercuric chloride intoxication.     

Effect of dietary copper and zinc levels on tissue copper,zinc, and iron in male rats

The interaction between dietary copper and zinc as determined by tissue concentrations of trace elements was investigated in male Sprague-Dawley rats. Animals were fed diets in a factorial design with two levels of copper (0.5, 5 μg/g) and five levels of zinc (1, 4.5, 10, 100, 1000 μg/g) for 42 d. In rats fed the low copper diet, as dietary zinc concentration increased, the level of copper decreased in brain, testis, spleen, heart, liver, and intestine. There was no significant effect of dietary copper on tissue zinc levels. In the zinc-deficient groups, the level of iron was higher in most tissues than in tissues from controls (5 μg Cu, 100 μg Zn/g diet). In the copper-deficient groups, iron concentration was higher than control values only in the liver. These data show that dietary zinc affected tissue copper levels primarily when dietary copper was deficient, that dietary copper had no effect on tissue zinc, and that both zinc deficiency and copper deficiency affected tissue iron levels.     

Iron-induced accumulation of hepatic metallothionein: the lack of glucocorticoid involvement

The process(es) by which parenteral iron effects the accumulation of hepatic metallothionein (MT) is not known. The present study examined glucocorticoids as potential mediators of this process. Chicks were given either one injection (ip) of iron (+1FE) at 10 mg Fe/kg, two injections of iron (+2FE) given 24 hr apart, or a single injection of saline. Plasma corticosterone was evaluated at various times following the last injection. Plasma corticosterone increased approximately 50% following +1FE but more than 200% at 2 and 4 hr following a second injection of iron (+2FE). Plasma zinc showed a transient increase followed by a considerable depression. Coincidentally, the accumulation (determined at 24 hr) of zinc MT in liver of +2FE chicks was three times higher than that of +1FE chicks. In another experiment, markedly greater changes, at similar time intervals, in plasma corticosterone were effected by multiple subcutaneous injections of adrenocorticotropic hormone (ACTH) (either 5 IU ACTH or 20 IU ACTH/kg). Subsequent analysis of hepatic zinc MT showed only minor changes as a result of ACTH injections. These results indicate that a change in the plasma glucocorticoid corticosterone is not a primary component in the process(es) by which parenteral iron effects an increase in hepatic zinc MT.     

Chronological changes in tissue copper, zinc and iron in the toxic milk mouse and effects of copper loading

The toxic milk (tx) mouse is a rodent model for Wilson disease, an inherited disorder of copper overload. Here we assessed the effect of copper accumulation in the tx mouse on zinc and iron metabolism. Copper, zinc and iron concentrations were determined in the liver, kidney, spleen and brain of control and copper-loaded animals by atomic absorption spectroscopy. Copper concentration increased dramatically in the liver, and was also significantly higher in the spleen, kidney and brain of control tx mice in the first few months of life compared with normal DL mice. Hepatic zinc was increased with age in the tx mouse, but zinc concentrations in the other organs were normal. Liver and kidney iron concentrations were significantly lower at birth in tx mice, but increased quickly to be comparable with control mice by 2 months of age. Iron concentration in the spleen was significantly higher in tx mice, but was lower in 5 day old tx pups. Copper-loading studies showed that normal DL mice ingesting 300 mg/l copper in their diet for 3 months maintained normal liver, kidney and brain copper, zinc and iron levels. Copper-loading of tx mice did not increase the already high liver copper concentrations, but spleen and brain copper concentrations were increased. Despite a significant elevation of copper in the brain of the copper-loaded tx mice no behavioural changes were observed. The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants.     

Effect of dietary nickel and iron on the trace element content of rat liver

The level and/or form of dietary iron, dietary nickel, and the interaction between them affected the trace element content of rat liver. Livers were from the offspring of dams fed diets containing 10–16 ng, or 20 μg, of nickel/g. Dietary iron was supplied as ferric chloride (30 μg/g) or ferric sulfate (30 μg, or 60 μg). In nickel-deprived rats fed 60 μg of iron/g of diet as ferric sulfate, at age 35 days, levels of iron and zinc were depressed in liver and the level of copper was elevated. At age 55 days, iron was still depressed, copper was still elevated, but zinc also was elevated. In rats fed 30 μg of iron/g of diet as ferric chloride, liver iron content was higher in nickel-deprived than in nickel-supplemented rats at 30, but not at 50, days of age. Also manganese and zinc were lower in nickel-deprived than in nickel-supplemented rats at age 35 days if their dams had been on experiment for an extended period of time (i.e., since age 21 days). Thus, the levels of copper, iron, manganese, and zinc in liver were affected by nickel deprivation, but the direction and extent of the affects depended upon the iron status of the rat.     

The effect of ethylmercury on fetal development and some essential metals levels in fetuses and pregnant female rats

Ethylmercuric chloride (EtHg), at the dose of 2.5 mg Hg/kg, was administered by gavage every other day to pregnant rats from d 6 to 20 of gestation. On the 21st day of gestation, females were sacrificed to allow the evaluation of embryotoxicity and take the material for analytical determinations. Copper, zinc, iron, and calcium were determined by AAS in liver, kidneys, brain, intestines of fetal and pregnant female rats, as well as in maternal spleen, whole blood, placenta, and fetal carcass. Ethylmercury caused a decrease of the body weight gain during gestation and diminution of relative liver weight of intoxicated females. This compound also induced fetotoxic effects, evidenced by slight diminution of the length as well as the weight of fetuses. It was found that the effect of EtHg on the levels of endogenous metals is different in females and fetuses. In pregnant females, EtHg administration resulted in a significant increase of copper levels in kidneys, liver, and spleen: and in the decrease of zinc concentration in the kidneys, but an increase in placenta and blood compared with pregnant controls. EtHg induced slight decrease of iron concentration in kidneys and intestinal wall of pregnant females. The concentrations of iron in liver and kidney and of zinc in whole blood and liver were lower in control pregnant rats than those in control non-pregnant females. In fetuses of EtHg-exposed mothers, increases in kidney zinc and liver calcium levels were found, whereas tissue copper and iron concentrations were the same as in controls.     

Iron and zinc status in rats with diet-induced marginal deficiency of vitamin A and/or copper

The hypothesis was tested that there are interactions of marginal copper and vitamin A deficiency regarding iron and zinc status. Copper restriction (1 vs 5 mg Cu/kg diet) significantly lowered copper concentrations in plasma and tissues of rats and reduced blood hemoglobin, hematocrit, and iron concentrations in tibia and femur, but raised iron concentrations in liver. Vitamin A restriction (0 vs 4000 IU vitamin A/kg diet) reduced plasma retinol concentrations and induced a fall of blood hemoglobin and hematocrit. Neither copper nor vitamin A restriction for up to 42 d affected feed intake and body wt gain. There were no interrelated effects of vitamin A and copper deficiency on iron status. Copper deficiency slightly depressed liver, spleen, and kidney zinc concentrations. Vitamin A deficiency lowered zinc concentrations in heart, but only when the diets were deficient in copper.     

Zinc, copper, and iron metabolism during porcine fetal development

Zinc, copper, and iron levels in maternal and fetal pig tissues and fluids were measured starting on d 30 of gestation and continuing to term (d 114) at 10-d intervals. Fetal hematocrit increased from a low of 19% on d 30 to 32% by d 50, after which it remained above 30% to term. Amniotic fluid zinc, copper, and iron all reached maximal levels by d 60 of gestation. Maternal serum zinc levels fluctuated little during gestation, but fetal serum zinc concentration was significantly elevated above maternal levels during the second trimester. Fetal serum copper levels were significantly lower than maternal values throughout gestation and this was also the case for ceruloplasmin oxidase activity. Maternal serum iron reached its lowest level by d 80 of gestation when rate of transfer of iron to the developing fetuses was high. Fetal serum iron declined throughout gestation, reaching its lowest level on d 100. In general, fetal liver concentrations of zinc, copper, and iron were higher than the corresponding maternal values throughout gestation. Distinct increases were noted for fetal hepatic zinc and copper concentrations during the second trimester of pregnancy and these were accompanied by increases in cytosolic and metallothionein-bound zinc and copper levels. Maternal hepatic iron declined during the second trimester, reaching its lowest point on d 80, indicative of the shunting of maternal iron reserves to fetal tissues. Fetal kidney metal levels did not demonstrate any distinctive developmental patterns with respect to zinc, copper, or iron concentrations, but a general accumulation of each metal was observed as gestation progressed. The results of this study highlight some of the distinct changes occurring in the metabolism of zinc, copper, and iron in both maternal and fetal tissues and fluids during gestation in the pig. Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other suitable products.     

Effects of rutin supplementation on antioxidant status and iron,copper, and zinc contents in mouse liver and brain

The effect of rutin on total antioxidant status as well as on trace elements such as iron, copper, and zinc in mouse liver and brain were studied. Mice were administrated with 0.75 g/kg or 2.25 g/kg P. O. of rutin for 30 d consecutively. Following the treatment, the activity of total antioxidant status, catalase, Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, zinc, copper, and iron were measured in mouse liver and brain. The results showed that rutin significantly increased the antioxidant status and Mn-superoxide dismutase activities in mouse liver, but it had no effect on these variables in the brain. Treatment with a higher concentration of rutin significantly decreased catalase activity and iron, zinc, and copper contents in mouse liver; it also resulted in a slower weight gain for the first 20 d. These results indicate that rutin taken in proper amount can effectively improve antioxidant status, whereas at an increased dosage, it may cause trace element (such as iron, zinc, and copper) deficiencies and a decrease in the activities of related metal-containing enzymes.     

Presence of acute phase changes in zinc, iron, and copper metabolism in turkey embryos

Acute phase changes in trace mineral metabolism were examined in turkey embryos. An endotoxin injection resulted in increased concentrations of serum copper and liver zinc and decreased concentrations of serum zinc in embryos incubated either in ovo or ex ovo. Changes in zinc and copper metabolism occurred when endotoxin either was injected intramuscularly, into the amnionic fluid, or administered onto the chorioallantoic membrane. Unlike poults, embryos did not respond to an inflammatory challenge with decreased serum iron concentrations. Acute phase changes in embryo serum zinc and copper as well as liver zinc concentrations were similar to those in poults. Increased liver zinc concentrations were associated with increased zinc in metallothionein (MT). An injection of a crude interleukin 1 preparation into embryos resulted in similar increases in hepatic zinc and MT concentrations as an endotoxin injection, suggesting a role for this cytokine in mediating the acute phase changes in embryonic zinc metabolism.     

Variable sensitivity to the glucocorticoid activity of cortisol in patients with primary adrenal insufficiency: assessment with ACTH profiles

Our aim was to investigate the usefulness of circulating levels of adrenocorticotropic hormone (ACTH) and also salivary cortisol to monitor cortisone substitution in patients with Addison's disease. 13 patients with primary adrenal insufficiency (8 women and 5 men, age 44 ± 11 years) received 12.5 mg cortisone acetate orally at 16:00 h and 25 mg at 07:00 h. Blood samples for cortisol and ACTH analysis were drawn every hour for 24 h, and also every half hour between 07:00 and 12:00 h. Samples for salivary cortisol were collected in parallel. Total ACTH levels showed large inter-individual variations and a diurnal rhythm with a nadir in the early evening at 19:00 (median 19 ng/l, range 2-434 ng/l) and high levels in the early morning, with a peak around 07:30 (median 844 ng/l, range 45-2,249 ng/l). Plasma cortisol concentrations showed 2 peaks distinct in time, but variable in height, 1-2 h after intake of cortisone. Plasma cortisol correlated significantly with ln(ACTH) at 17:00 h (r=-0.56), at 10:00 h (r=-0.51), and at 10.30 h (r=-0.57). When tested at different time points, ln(ACTH) at 10:00 to 12:00 h was negatively correlated with plasma cortisol between 08:30 and 12:00 h. Plasma cortisol was highly correlated to ln(salivary cortisol) most of the time points measured, but 30-60 min after intake of cortisone acetate the correlation disappeared. In conclusion, the large interindividual variation in ACTH levels most likely indicates varying sensitivity to cortisol with a need for individualized dosing schemes. Furthermore ACTH-determinations may be useful for dose titration of cortisol.     

Trace element levels in the liver of rats with acute and chronic fascioliasis and after treatment with zinc-copper hydroxochloride mixed crystals

Quantities of trace elements including copper, zinc, cobalt, manganese and iron were investigated in the liver tissue of rats at the acute or chronic stages of fascioliasis following treatment with zinc-copper hydroxochloride mixed crystals. Oral dosing (with food) of zinc-copper mixed crystals to healthy rats increased zinc and copper levels in the liver and decreased the iron content compared with controls. Manganese and cobalt levels did not change significantly. Significant reductions in all trace elements except manganese occurred in the liver of rats with acute or chronic fascioliasis. Manganese levels were slightly increased in rats at the acute stage and slightly decreased in rats at the chronic stage of fascioliasis. The application of mixed zinc-copper crystals at the acute or chronic stages of fascioliasis lead to a restoration of zinc and copper levels and a slight reduction in the iron levels in liver tissue of rats. The beneficial effects of applied salts were more apparent in rats chronically infected with Fasciola hepatica.     

Extrahepatic tissue copper concentrations in white perch with hepatic copper storage

Hepatic copper storage in man (Wilson's disease), Bedtington and West Highland white terriers, and white perch ( Morone americana ) is characterized by the progressive accumulation of copper in hepatic lysosomes bound to cytoprotective metallothionein. In man, saturation of the liver storage capacity results in the distribution of copper to extrahepatic tissues with multiple organ system dysfunction. To determine if extrahepatic tissue copper concentrations also increase in white perch, copper and zinc levels in liver, brain, heart, gills, serum, and bile were determined by atomic absorption spectrophotometry and compared to striped bass ( Morone saxatilis ). Results showed that brain copper concentrations in. white perch were elevated and significantly correlated with liver copper. Bile and serum copper also increased significantly with liver copper. Copper levels in heart and gill tissues were low. Liver zinc was increased in white perch but not to the same magnitude as copper, and was correlated significantly with liver copper; possibly a non-specific secondary increase related to an overall increase in hepatic metallothionein. Histochemical staining of liver with rubeimc acid for copper was proportional to copper concentrations, and clusters of positive mononuclear cells were also seen in brain and spleen. Foci of macrophages in spleen were also intensely positive with Perl's iron stain which may have been indicative of haemolysis. The patterns of copper distribution seen in white perch present a useful comparative model to study alterations in copper metabolism.     

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 2³ 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.     

Increased ACTH and cortisol secretion after interleukin-alpha injection in the common marmoset (Callithrix jacchus jacchus)

We have studied the effect of intravenous injection of interleukin-1 (dose range: from 0.25 to 4.5 microg/kg of body weight) on plasma ACTH and cortisol levels in the marmoset, a primate paradygm of peripheral glucocorticoid resistance. Blood sampling were collected and body temperature recorded 0, 15, 30, 60, 120, 180, 240 and 300 min after injection. Interleukin-1 stimulated secretion of ACTH in a dose-dependent fashion. Maximal secretion occurred 120 min after injection, and lasted up to 240 min. Plasma ACTH levels returned to baseline 300 min after interleukin-1 injection. Plasma cortisol levels were related to ACTH levels. Body temperature elevation, which occurred 10-15 min after injection was dose-dependent, and lasted 3 h. Results suggest that the pyrogenic effect of interleukin is associated, in the marmoset, with integrated activation of the hypothalamic-pituitary-adrenal axis. In light of the proneness of marmosets to hyperimmune disorders, our data are consistent with the hypothesized central biological role of IL-1, as well as the pathophysiological relevance of the neuro-endocrine-immune cross-talk during the acute phase response.     

The effect of serotonin agonist 1-(trifluoromethylphenyl)-piperazine on corticotropin releasing factor and arginine vasopressin in rat hypothalamic nuclei

Effects of 1-(m-trifluoromethylphenyl)-piperazine, a serotonin agonist, were examined on rat plasma levels of adrenocorticotropin (ACTH) and arginine vasopressin (AVP), and on hypothalamic contents of corticotropin releasing factor (CRF) and AVP, to investigate the role of brain serotonin in ACTH regulation. Both plasma ACTH and AVP levels increased markedly 30 min after injection of the compound and were still elevated at 80 min. CRF and AVP contents in the median eminence decreased 30 min after injection but returned to the basal levels by 80 min. The AVP content in the supraoptic nucleus was elevated 80 min after injection. The CRF and aVP content did not significantly change in the paraventricular, suprachiasmatic and arcuate nuclei. Serotonin or 1-(m-trifluoromethylphenyl)-piperazine did not stimulate the release of ACTH in pituitary cell cultures. These results suggest that both CRF and AVP were secreted into the portal vessels by 1-(m-trifluoromethylphenyl)-piperazine to release ACTH from the anterior pituitary and that both the ACTH and AVP release were stimulated via the brain serotonergic mechanism.     

Effect of low dietary rubidium on plasma biochemical parameters and mineral levels in rats

The effects of low dietary rubidium on plasma biochemical parameters and mineral levels in tissues in rats were studied. Eighteen male Wistar rats, weighing about 40 g, were divided into two groups and fed the diets with or without supplemental rubidium (0.54 vs 8.12 mg/kg diet) for 11 wk. Compared to the rats fed the diet with supplemental rubidium, the animals fed the diet without rubidium supplementation had higher urea nitrogen in plasma; lower rubidium concentration in tissues; lower sodium in muscle; higher potassium in plasma, kidney and tibia, and lower potassium in testis; lower phosphorus in heart and spleen; lower calcium in spleen; higher magnesium in muscle and tibia; higher iron in muscle; lower zinc in plasma and testis; and lower copper in heart, liver, and spleen, and higher copper in kidney. These results suggest that rubidium concentration in tissues reflects rubidium intake, and that rubidium depletion affects mineral (sodium, potassium, phosphorus, calcium, magnesium, iron, zinc, and copper) status.     

The trace element composition of the organs and tissues of animals administered a highly dispersed powder and copper sulfate

Changes in the content of microelements in blood, heart and liver after a single subcutaneous injection of aquatic suspension of highly dispersed powder and copper sulphate in different doses were investigated. Injection of highly dispersed powder and copper sulphate was shown increase phase fluctuations of copper, zinc and iron level in all organs under study. It was demonstrated that irrespective of the form and dose of injection copper does not break interrelation modus between zinc and copper, characteristic of the control and does not change zinc/copper ratio. Bioavailability of highly dispersed copper powder injected in organism at the dose 0.2 mg/kg was found to be somewhat higher than that of sulphate.     

Trace element levels in the experimental peritonitis

Electron transfer from iron or copper ions to oxygen is an important example of cellular free radical initiation. Oxygen derived free radicals have been implicated as mediators of cellular injury in several model systems. To evaluate the importance of iron, copper and zinc levels on lipid peroxidation in peritonitis, we measured peritoneum malondialdehyde (MDA) as a marker of lipid peroxidation, zinc, copper, and iron levels during an animal model of intraperitoneal sepsis. Additionally the effects of the free radical scavenger alpha-tocopherol administration was studied. The peritoneum MDA, iron, copper and zinc levels were increased after induction of peritonitis with Escherichia Coli. The treatment with alpha-tocopherol was decreased the peritoneum MDA, iron and copper levels significantly, except the zinc level (p < 0.001, p < 0.001, p < 0.001, respectively). Additionally the alpha-tocopherol treatment for three days prior to injection of E.Coli more decreased MDA, copper and iron levels than that of the treatment with alpha-tocopherol at the time of injection of E. Coli (p < 0.001, p < 0.001, p<0.001, respectively). Our results indicated that copper, iron and zinc had important effects on peroxidation events in E. Coli induced peritonitis, and alpha-tocopherol treatment can improve the oxidant status.     

Influence of intracerebroventricular (ICV) injection of ACTH (1-24) on plasma gonadotropin in female rats: dose-response study

The intracerebroventricular (ICV) injection of ACTH (1-24) (0.1, 1.0 and 2.5 micrograms) to adult conscious ovariectomized (OVX) rats caused a dose-related inhibition of plasma LH at 10 min postinjection. The ICV injection of ACTH (1-24) (2.5 micrograms) to OVX rats in the absence or presence of a single dose of estradiol benzoate (OVX + EB): a) Decreased significantly plasma LH levels in OVX rats at 10 and 30 min postinjection. b) Decreased significantly plasma LH levels in (OVX + EB) rats at 10 min but not at 30 min postinjection. c) Did not change plasma FSH levels at 10 or 30 min postinjection in both (OVX) or (OVX + EB) rats. d) Did not change plasma ACTH levels at 10 or 30 min postinjection in (OVX) rats. Our observation suggest that ACTH (1-24) inhibited plasma LH, possibly through brain sites of action.