Electrolyte composition of cow and calf tissues in health and in acute digestive disturbances]

Sodium, potassium, calcium, magnesium, manganese, zinc and chloride contents in the blood plasma of calves at parturition have been established to correspond to their levels in blood of cows during their calving period. Iron and inorganic phosphorus contents in calves blood plasma appeared to increase and copper content to be lower in this period as compared to postnatal period. By the third day of postnatal ontogenesis sodium concentration in calves blood decreased, copper level increased and the rest indices of water-salts metabolism in calves and adult animals were alike. Digestion disturbances in the calves were accompanied by changes in levels and magnitude of Na+/K+ ratio, magnesium, iron, copper, manganese and zinc contents in blood, liver and kidneys as well as Ca++/Pi ratio in mitochondria and cytosol of liver and jejunum mucose layer cells in comparison with clinically healthy animals.     

Evaluation of the protective activity of deferiprone, an aluminum chelator, on aluminum-induced developmental toxicity in mice

BACKGROUND: Since deferiprone can be an effective chelating agent for the treatment of aluminum (Al) overload, in the present study we investigated whether this chelator could protect against Al-induced maternal and developmental toxicity in mice. METHODS: A single oral dose of Al nitrate nonahydrate (1,327 mg/kg) was given on gestation day 12, the most sensitive time for Al-induced maternal and developmental toxic effects in mice. At 2, 24, 48, and 72 hr thereafter, deferiprone was given by gavage at 0 and 24 mg/kg. Cesarean sections were performed on day 18 of gestation and fetuses were examined for malformations and variations. RESULTS: Aluminum-induced maternal toxicity was evidenced by significant reductions in body weight gain, corrected body weight change, and food consumption. Developmental toxicity was evidenced by a significant decrease in fetal weight per litter and an increase in the total number of fetuses and litters showing bone retardation. No beneficial effects of deferiprone on these adverse effects could be observed. By contrast, a more pronounced decrease in maternal weight gain and corrected body weight change, as well as a higher number of litters with fetuses showing skeletal variations was noted in the group exposed to Al nitrate and treated with deferiprone at 24 mg/kg. CONCLUSIONS: According to the current results, deferiprone would not be effective to prevent Al-induced maternal and embryo/fetal toxicity in mice.     

Distribution patterns of trace metals and of lipid peroxidation in plasma and erythrocytes of rat exposed to aluminum

Significant decreases of the hematocrit, hemoglobin, and plasma iron levels were observed in rats receiving daily intraperitoneal injections of aluminum at a dose of 27 mg Al/kg body wt for 3 wk, as compared to untreated controls. The activity of alkaline phosphatase was also significantly lower in the treated animals as a result of the accumulation of aluminum in the liver (p<0.05). Following aluminum administration, the plasma concentrations of aluminum and copper were also significantly increased, whereas the plasma zinc levels and oxidative stress measured through thiobarbituric acid reaction products showed nonsignificant differences between the two groups (p>0.05). The erythrocyte concentrations of aluminum, copper, zinc, and iron and of superoxide dismutase activity were found to be significantly higher in the study group as compared to controls. The treated animals also showed evidence of higher oxidative stress in comparison to controls. These results suggest that erythrocyte aluminum accumulation could result in abnormal trace element homeostasis and increasing oxidative stress, which might be a mechanism of aluminum-induced anemia.     

Transition metal abnormalities in progressive dementias

Abnormal distributions of transition metals inside the brain are potential diagnostic markers for several central nervous system diseases, including Alzheimer’s disease (AD), Parkinson’s disease, dementia with Lewy bodies (DLB), bipolar disorders and depression. To further explore this possibility, the total concentrations of iron, zinc, copper, manganese, aluminum, chromium and cadmium were measured in post-mortem hippocampus and amygdala tissues taken from AD, DLB and Control patients. A statistically significant near fifty percent reduction in the total copper levels of AD patients was observed in both the hippocampus and amygdala. The statistical power of the hippocampus and amygdala copper analysis was found to be 86 and 74% respectively. No statistically significant deviations in the total metal concentrations were found for zinc, manganese, chromium or aluminum. Iron was found to be increased by 38% in AD amygdala tissues, but was unchanged in AD hippocampus tissues. Accounting for differences in tissue water content, as a function of both tissue type and disease state, revealed more consistencies with previous literature. To aid in the design of future experiments, the effect sizes for all tissue types and metals studied are also presented.     

Studies of Zn, Mg, Cu, Ca and Fe in cadmium poisoned toads before and after treatment with EDTA

Zn, Mg, Cu, Ca and Fe were determined spectrophotometrically in liver, kidneys, muscle, spleen and blood of Bufo regularis after a single i.m. injection of 6.2 mg Cd/kg (which represents the 96 hr LD50) alone or in combination with 40 mg EDTA/kg (the minimal EDTA concentration causing 100% survival over that period). Cadmium administration caused recognizable effects on the essential metals levels in different tissues and organs. In the majority of the tissues and organs studied, zinc and copper concentrations returned to their normal ranges in animals that received both cadmium and EDTA. In contrast, magnesium, calcium and iron contents not only returned back to their control values but also exceeded them.     

Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis

The role of trace elements in the pathogenesis of liver cirrhosis and its complications is still not clearly understood. Serum concentrations of zinc, copper, manganese and magnesium were determined in 105 patients with alcoholic liver cirrhosis and 50 healthy subjects by means of plasma sequential spectrophotometer. Serum concentrations of zinc were significantly lower (median 0.82 vs. 11.22 micromol/L, p < 0.001) in patients with liver cirrhosis in comparison to controls. Serum concentrations of copper were significantly higher in patients with liver cirrhosis (median 21.56 vs. 13.09 micromol/L, p < 0.001) as well as manganese (2.50 vs. 0.02 micromol/L, p < 0.001). The concentration of magnesium was not significantly different between patients with liver cirrhosis and controls (0.94 vs. 0.88 mmol/L, p = 0.132). There were no differences in the concentrations of zinc, copper, manganese and magnesium between male and female patients with liver cirrhosis. Only manganese concentration was significantly different between Child-Pugh groups (p = 0.036). Zinc concentration was significantly lower in patients with hepatic encephalopathy in comparison to cirrhotic patients without encephalopathy (0.54 vs. 0.96 micromol/L, p = 0.002). The correction of trace elements concentrations might have a beneficial effect on complications and maybe progression of liver cirrhosis. It would be recommendable to provide analysis of trace elements as a routine.     

Levels of trace elements in the liver and diet of free-living koalas, Phascolarctos cinereus (Goldfuss)

The mean liver concentrations of copper, manganese, zinc and cobalt were 0.25, 0.20, 2.97 mmol/kg and 2.81 mumol/kg respectively in free-living koalas in Victoria, Australia. The mean plasma copper concentration was 9.2 mmol/liter which was somewhat below the level in other hindgut fermenters. The mean concentrations of copper, manganese and zinc in their diet (Eucalyptus spp.) were 0.08, 4.46 and 0.27 mmol/kg respectively. Analysis of the data established a significant correlation between the age of the koalas and the inverse of the concentration of the copper (r = -0.67, P less than 0.001) in the liver. There were no such correlations apparent for manganese, zinc or cobalt. The concentrations of trace metals in the Eucalyptus diet for the koala were comparable to those recommended in the diets for other hindgut fermenters such as horse, rabbits and rats. However there was evidence for suboptimal plasma copper levels (mean 9.2 mmol/liter) in some koalas, and reduced liver copper levels in older koalas. Liver histology revealed the presence of brown intracytoplasmic granules in hepatocytes. The size and number of these granules per cell was noted to increase with increasing age of the koala but the chemical nature and the role of the granules was not determined by the histochemical techniques used.     

Effects of interaction between65Zn,cadmium, and copper in rats

Distribution and retention of zinc in the presence of cadmium and copper was studied in rats exposed repeatedly to these metals. The experiment was performed on white rats of the Wistar strain. The animals were divided into four groups/five rats each: 1)⁶⁵ZnCl₂; 2)⁶⁵ZnCl₂+CdCl₂; 3)⁶⁵ZnCl₂+CuCl₂; and 4) control group. Rats were administered sc every other day for two weeks:⁶⁵ZnCl₂−5 mg Zn/kg; CdCl₂−0,3 Cd/kg; and CuCl₂−2 mg Cu/kg. The zinc content was measured in rat tissues by γ-counting. Effect of Cd and Cu on subcellular distribution of zinc in the kidney and liver and on the level of metallothionein were also examined. Whole body retention of zinc under the influence of cadmium was lower than that observed in animals treated with zinc alone. However, copper increased twofold the whole body retention of zinc. Cadmium elevated the accumulation of zinc only in the kidneys nuclear fraction and liver soluble fraction. In the kidneys and liver, copper elevated the accumulation of zinc, in the nuclear, mitochondrial, and soluble fractions. The level of metallothionein-like proteins (MT) in the kidneys after a combined supply of zinc and copper was significantly increased with respect to the group of animals treated with zinc alone. These results indicated complex interactions between cadmium, copper, and zinc that can affect the metabolism of each of the metals.     

Effects of oral aluminum on essential trace elements metabolism during pregnancy

The present study was conducted to assess in rats the effects of oral aluminum (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) accumulation and urinary excretion. Three groups of plug-positive Sprague-Dawley (SD) rats were given by gavage 0, 200, and 400 mg/kg/d of Al(OH)₃ on gestational days 1–20. Three groups of nonpregnant female SD rats of the same age received Al(OH)₃ by gavage at the same doses for 20 consecutive days. At the end of the treatment period, 24-h urine samples were collected for analysis of Al and essential elements. Subsequently, all animals were sacrificed and samples of liver, bone, spleen, kidneys, and brain were removed for metal analyses. With some exceptions, the urinary amounts of Al, Mn, and Cu excreted by pregnant animals as well as the urinary levels of Al excreted by nonpregnant rats were higher in the Al-treated groups than in the respective control groups. Although higher Al levels were found in the liver of pregnant rats, the concentrations of Al in the brain of these animals were lower than those found in the same tissues of nonpregnant rats. With regard to the essential elements, tissue accumulation was most affected in pregnant than in nonpregnant animals. In pregnant rats, the hepatic and renal concentrations of Ca, Mg, Mn, Cu, Zn, and Fe, as well as the levels of Ca in bone, and the concentrations of Cu in brain were significantly higher in the Al-exposed groups than in the control group. According to the current results, oral Al exposure during pregnancy can produce significant changes in the tissue distribution of a number of essential elements.     

Phostoxin-induced biochemical and pathomorphological changes in rabbits

The effect of chronic phostoxin administration on some tissue ATPases, hematology and tissue histopathology was investigated using a combination of gravimetric, enzymatic, colorimetric and histological procedures in New Zealand White rabbits after 2 weeks administration of 0.8mg phostoxin/kg body weight/day, po. The phostoxin treatment led to significant decreases in Na(+)-K+ ATPase activities in renal, hepatic and cardiac tissues. Similar decreases were obtained in the activities of Ca(2+)-ATPase and Mg(2+)-ATPase in liver. In addition, the phostoxin-toxified rabbits manifested significant decreases in hematocrit, red blood cell count, hemoglobin and platelets. Histological examination of the tissues revealed pronounced degenerative changes in liver, heart and kidney.     

Influence of sex,strain, and species on trace metal status of insulin-deficient diabetic rodents

Previous studies have demonstrated marked alterations in trace metal metabolism in male Sprague-Dawley rats following chemical induction of the diabetic state. To determine whether such changes represented a general response to the insulin-deficient condition the levels of zinc, copper, and maganese in liver, kidney, and intestine of normal and streptozotocin (STZ)-diabetic male rats of the Sprague-Dawley, Wistar, and Long-Evans strains, female Sprague-Dawley rats, and male mice were measured. Significantly increased concentrations of zinc, copper, and maganese in liver, and zinc and copper in kidney were found in STZ-diabetic rats, regardless of sex and strain. In contrast, the zinc and copper contents in liver and kidney of control and STZ-diabetic mice were similar, but hepatic manganese levels were significantly elevated in both organs of the diabetic mouse. The concentrations of all three metals were similar in the intestine of control and diabetic rodents. Higher amounts of zinc and copper were bound to metallothionein in the liver and kidney of the diabetic rats. Nicotinamide injection prior to STZ administration protected rats against the development of diabetes and alterations in trace metal status. These data indicate that specific alterations in the metabolism of zinc, copper and manganese during episodes of pancreatic hormonal imbalance represent a general phenomenon in the rat. A possible explanation for the differential response of the STZ-diabetic mouse is discussed.     

Studies on the effects of x-ray on erythrocyte zinc and copper concentrations in rabbits after treatment with antioxidants

The aim of this study was to investigate the effect of supplemental antioxidant vitamins and minerals on the erythrocyte concentrations of zinc and copper in rabbits after exposure to X-rays. The animals were divided into two experimental and one control group (CG). The first group (VG) was given daily oral doses of vitamins E and C; supplemental amounts of managanese, zinc, and copper were mixed with the feed and given to the second group of experimental animals (MG). Blood samples were taken from all groups before and after 4 wk of vitamin and mineral administration and after irradiation with a total dose of 550-rad X-rays. The administration of minerals caused the most significant increases of Zn and Cu. Even after irradiation, the zinc levels in the irradiated animals were higher than in the nonirradiated vitamin-supplemented animals (p<0.05). The results suggest that supplementation with antioxidant vitamins and minerals may have a protective effect against X-ray-induced damage.     

Effect of cadmium and aluminum intake on the antioxidant status and lipid peroxidation in rat tissues.

This work aimed to study the relationship between the accumulation of cadmium (Cd) or aluminum (Al) in certain tissues and the levels of lipid peroxides as well as tissue antioxidants. To carry out such investigations, CdCl2 was given to rats in two dose levels; 0.5 or 2.0 mg/kg i.p for 1 day or daily repeated doses for 2 weeks. Al was given as AlCl3 either in a single dose of 100 mg/kg or daily repeated doses of 20 mg/kg for 2 and 4 weeks. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation) and reduced glutathione (GSH) levels as well as the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) enzymes. Liver and kidney functions were assessed by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities as well as serum urea and creatinine concentrations. Cd and Al concentrations in the studied tissues were also measured. Results indicated that tissue Cd was significantly increased after administration of either Cd doses. After a single dose of 0.5 or 2.0 mg/kg CdCl2, the increase in tissue Cd levels were accompanied by an increase in MDA and a decrease in GSH levels. On the other hand, after repeated administration of Cd, tissue Cd accumulation was accompanied by increased hepatic and renal GSH levels with decrease in MDA content and a decrease in GSH-PX activity in liver. Liver function was affected at all dose regimens, whereas kidney function was affected only after 2 weeks administration of the higher dose. In Al treated rats, Al concentration was shown to be increased in liver much more than in brain. This was accompanied by a slight decrease in hepatic GSH level after 2 weeks and a decrease in GSH-PX activity after 4 weeks. Liver function was affected only after repeated injection of Al for 2 or 4 weeks. In general, Al administration exhibited safer pattern than Cd.     

Copper, zinc, iron, and manganese accumulation in cattle from Asturias (northern Spain)

Monitoring levels of mineral concentrations in animal tissues is important for assessing the effect of contamination on animal health and safety of animal origin products in human nutrition. This study evaluated the levels of certain trace elements (copper, zinc, iron, and manganese) in cattle from an industrial and mining region in the north of Spain (Asturias). Samples of 312 animals aged 9–12 mo were collected from the whole region and analyzed after acid digestion using atomic absorption spectrophotometry (AAS). The geometric mean concentrations obtained per wet weight for the liver, kidney, muscle, and blood were 34.3 mg/kg, 4.04 mg/kg, 1.65 mg/kg, and 0.651 mg/L for copper, respectively, and 38.5 mg/kg, 23.0 mg/kg, 47.0 mg/kg, and 2.44 mg/L for zinc, respectively. For iron, blood was not analyzed and results were 96.2 mg/kg, 105 mg/kg, and 56.0 mg/kg for the liver, kidney and muscle, respectively. For manganese, only the liver and kidney were analyzed, and the results were 3.11 mg/kg and 1.19 mg/kg, respectively. There was no evidence of an accumulation of toxic levels of trace metals in Asturian cattle. Females accumulated more iron in the liver (p<0.001, F _1,310=18.4) and the kidney (p<0.001, F _1,310=13.5) and more manganese in the liver (p<0.01, F _1,310=9.55) than males.     

Mineral content of blood serum in greenland seal pups during the period of adaptation to the captivity

Results of investigation of mineral levels in the harp seal pups blood serum in connection with adaptation to the captivity are presented. The contents of copper, zinc, iron, magnesium, cobalt, manganese, sodium, potassium, calcium and phosphorus in the first 18 day of animals keeping in the oceanarium were determined. The causes of the revealed differences in changes of the contents of single elements during the observation term, and also question on duration of fading stress alterations and stabilization of biochemical parameters of marine mammals blood are discussed.     

Chelating effect of novel pyrimidines in a model of aluminum intoxication

Long time ago aluminum (Al) was considered as a non-toxic element and its use had no restrictions. However, over the last two decades, scientific publications have indicated that Al is a toxic element. In line with this, aluminum accumulation in the organism is associated with a variety of human pathologies. Efficient therapeutics approach to treat Al intoxication are still not available, but there is a consensus that chelation therapy is the procedure to be used. However, the development of new chelating agents are highly desirable to improve the efficacy of the treatment of Al intoxication. The present study evaluates the chelating effect of two novel pyrimidines: 4-tricloromethyl-1-H-pyrimidin-2-one (THP) and (4-methyl-6-trifluoromethyl-6-pyrimidin-2-il)-hydrazine (MTPH) in a mice model of aluminum intoxication and compares their efficacy with those of desferrioxamine (DFO), a classical agent used for treat Al accumulation. The animals were exposed to aluminum by gavage (0.1 mmol aluminum/kg/day) 5 days/week for 4 weeks. At the end of this period, DFO was injected i.p. and the novel pyrimidines were given by gavage at 0.2 mmol/kg/day for five consecutive days. Aluminum concentration in tissues (brain, liver, kidney and blood) was determined by graphite furnace atomic absorption spectroscopy (GFAAS). The results showed that when administered by gavage, aluminum accumulated in the brain, kidney and liver of mice. MTPH was able to decrease aluminum levels in aluminum plus citrate animal groups, whereas THP was inefficient for this purpose. However, the novel pyrimidines used in this study were unable to surpass the aluminum chelating property of DFO. Thus, new studies must be performed utilizing other chelating agents which can decrease aluminum toxicity.     

Effects of tin and lead on organ levels of essential minerals in rabbits

The effect of tin and lead on levels of essential metals (Zn, Cu, Ca, Fe) in rabbit tissues was compared in relation to the route of administration. Animals received intraperitoneally, or per os, SnCl2 (2 mg Sn/kg) or Pb(CH3COO)2 (3.5 mg Pb/kg) every day for 5 d or for 1 mo. Copper, zinc, iron, and calcium were determined by AAS in the liver, kidneys, spleen, brain, bone marrow, and blood; lead and tin concentration were measured in the blood of animals. Tin and lead administered per os caused either no changes or the decreased concentration of endogenous metals in several tissues. The other route of administration (ip) of both metals generally contributed to the increased storage of essential elements. Blood tin levels of tin treated animals were only about less than or equal to 1/10 of blood lead concentrations of rabbits exposed to lead.     

Production of hypotaurine, taurine and sulfate in rats and mice injected with L-cysteinesulfinate

Summary. We studied in vivo production of taurine, hypotaurine and sulfate following subcutaneous administration of L-cysteinesulfinate (CSA) to rats and mice. When 5.0 mmol/kg of body weight of CSA was injected to rats, increased urinary excretions of taurine, hypotaurine and sulfate in 24 h urine were 617, 52 and 1,767 μmol/kg, respectively. From these results together with our previous data, sulfate production was calculated to be 1.6 times greater than taurine production. Increased contents (μmol/g of wet tissue) over the control of taurine and hypotaurine in mouse tissues at 60 min after the injection of 5.0 mmol/kg body weight of CSA were: liver, 3.5 and 9.9; kidney, 0.3 and 5.2; heart, 3.7 and 0.2; blood plasma, 0.4 and 0.2, respectively. Upon loading of hypotaurine or taurine, tissue contents of these amino acids in liver and kidney increased greatly. Our results indicate that liver is the most active tissue for taurine production, followed by kidney, and that external CSA, hypotaurine and taurine are easily taken up by these tissues.     

Zinc status does not affect aluminum deposition in tissues of rats

To examine whether zinc deficiency would increase the toxicity of dietary aluminum, weanling, male Sprague-Dawley rats were fed purified diets containing either 2 or 30 mg Zn/kg diet, with or without 500 mg Al/kg diet for 28 d. Individually pair-fed rats were fed the 30 mg Zn/kg diet with or without added aluminum to control for inanition secondary to zinc deficiency. Rats fed the 2 μg Zn/kg diet showed evidence of zinc deficiency, including anorexia, growth retardation, and depressed concentrations of zinc in tibias and livers. Zinc deficiency did not significantly increase the concentrations of aluminum in the tibias, livers, kidneys, or regions of the brain examined (cerebrum, cerebellum, midbrain, and hippocampus). Inclusion of aluminum in the diet did not alter aluminum concentrations in the various tissues. Under the conditions of this study, zinc deficiency did not result in greater sensitivity to dietary aluminum exposure.