Effects of etretinate on the distribution of elements in rats

We studied in the rat the effects of the drug etretinate (Tigason), given at three doses 3, 10, and 30 mg/kg body wt for 1 mo, on the concentrations of Na, K, Ca, Mg, Fe, S, P, Cu, and Zn in the plasma, brain, thymus, heart, liver, lung, kidney, testicle, muscle, and bone. The elements were simultaneously determined in tissues after nitric acid dissolution by inductively coupled plasma emission spectrometry using a JY 48 instrument. At the dose of 3 mg/kg, etretinate did not induce any statistically significant modifications of the element distribution. At the dose of 10 mg/kg, the main observed modifications were in plasma an increase of copper (+38%) and a decrease of zinc (-25%). At the highest dose of 30 mg/kg, some variations of the concentrations of elements in tissues were observed. But, on no account did retinoids induce an alteration of the mineral composition of bone, despite obvious macroscopic bone alterations.     

Iron,copper, and zinc status in rats fed supplemental nickel

Literature data concerning the effect of increasing dietary Ni concentrations on Fe, Cu, and Zn status in rats are sparse and, in part, controversial. Therefore, the effects of the addition of either 0, 3, 50, or 100 mg Ni/kg diet on Fe, Cu, and Zn status of rats were investigated in two separate experiments. Purified diets were used that were composed according to the established nutrient requirements of rats. Ni in kidney was increased with increasing Ni intakes. Dietary Ni did not significantly influence Fe concentrations in plasma, liver, kidney, femur, and spleen. Likewise, the addition of Ni to the diet did not alter Cu status. Zn concentrations in femur were significantly decreased after feeding the diets with 100 mg Ni/kg. However, Zn in plasma, liver, kidney, and spleen was not affected. It is concluded that variations in dietary Ni concentrations have no major impact on Fe, Cu, and Zn status in rats.     

Gut retention of metals in rats

In sucklings, a high fraction of orally administered metals and radionuclides is retained in the gut. The location of elements in the gut is of interest because of their potential local health effect. The purpose of this work was to evaluate the influence of chelation therapy on gut retention and location of cadmium, mercury, and cerium in-suckling rats. Radionuclides^115mCd,²⁰³Hg, and¹⁴¹Ce were administered orally to 6-d-old rats. Chelating agent Zn-DTPA (3.64 mmol/kg) was administered to animals that received^115m Cd or¹⁴¹Ce and Na-DMPS (375 μmol/kg) to those that received²⁰³Hg, immediately and 24 h or 24 and 48 h after radionuclide administration. Radio-activity was determined in the whole body and gastrointestinal tract 6 d later. Both early and delayed chelation treatment very effectively reduced whole body retention, and this was mainly owing to reduced gut retention. Although chelation therapy reduced gut retention of administered radionuclides 3–30 times, the site of metal accumulation and retention in the intestine remained unchanged. For all 3 radionuclides, both after early and delayed therapy, the site of metal accumulation was always the lower part of small intestine—ileum.     

Tissue distribution and urinary excretion of essential elements in rats orally exposed to aluminum chloride

The purpose of this study was to determine disorders in the metabolism of the essential elements (Ca, Fe, Cu, and Zn) in some tissues of rats, as well as to detect the dynamics of urinary excretion of these metals after oral administration of 20 mgAl/kg every day for 8 wk. The elements were determined in brain, kidneys, blood, and urine of the animals in 1st, 2nd, 3rd, 4th, and 8th wk after the exposure to AlCl₃. After the 1st wk of aluminium administration, we observed increase of Ca and a decrease of Fe in blood. In brain Ca, Fe, and Cu concentrations were significantly higher in Al-treated rats than in controls after 8-wk exposure. The concentration changes of the essential metals in the tissue were accompanied by increase of the Ca, Fe, and Zn urinary excretion. We assume that the increase in urinary excretion of Ca and the decrease of Fe in the blood may be sensitive indicators of oral aluminium administration.     

The distribution of cadmium within the human prostate

Five normal prostates from autopsies of humans aged 61-76 yr were divided into 2 x 24 topographically well-defined pairs of slices that were analyzed for cadmium (Cd) and examined histologically. The corresponding kidney cortex concentrations were also determined. The concentrations in ng Cd/g wet wt were in the range of 50-500 in the prostates and 8,000-39,000 in the kidneys with good mutual correlation. Large variations in Cd concentrations within the prostates were found. The concentrations were highest at the base (near the bladder) and lowest at the apex of the gland. Furthermore, large variations within horizontal layers were found, and this variation was not correlated to the histological amount of stroma or glands.     

Manganese status,gut endogenous losses of manganese,and antioxidant enzyme activity in rats fed varying levels of manganese and fat

We hypothesized that manganese deficient animals fed high vs moderate levels of polyunsaturated fat would either manifest evidence of increased oxidative stress or would experience compensatory changes in antioxidant enzymes and/or shifts in manganese utilization that result in decreased endogenous gut manganese losses. Rats (females in Study 1, males in Study 2,n = 8/treatment) were fed diets that contained 5 or 20% corn oil by weight and either 0.01 or 1.5 μmol manganese/g diet. In study 2,⁵⁴Mn complexed to albumin was injected into the portal vein to assess gut endogenous losses of manganese. The manganese deficient rats:

Levels of some trace elements in selected autopsy organs,and in hair and blood samples from adult subjects of the Italian population

This study, which is part of a research program for the determination of trace element reference levels in various human tissues for the Italian population, presents the concentrations of Se, Hg, Cr, Cs, Sc, Rb, Zn, Fe, Co, and Sb in lung, liver, spleen, and kidney autopsy samples taken from 14 adult subjects of the Italian population who died from accidental causes. Concentrations of the same trace elements are given also for blood and hair samples taken from subjects of the general Italian population and of a population group living in a small coastal town that has an average annual fish consumption well above the national average. The analytical method used was Instrumental Neutron Activation Analysis. The levels and distribution of the trace elements in the various human organs examined are analyzed and discussed.     

The effect of silicon (Si) on lipid parameters in blood serum and arterial wall

The influence of silicon treatment on the levels of lipid parameters of blood serum and aortic wall was studied in rats. The concentrations of total cholesterol, phospholipids, triglycerides, HDL-cholesterol, LDL-cholesterol, and HDL-phospholipids were measured in sera of rats receiving per os a soluble, inorganic silicon compound--sodium metasilicate nonahydrate (Na2SiO3.9H2O)--dissolved in the drinking water. In the aortic tissue levels of total cholesterol, triglycerides and phospholipids were estimated. An increase in HDL-cholesterol and HDL-phospholipid concentrations, with a simultaneous decrease of LDL-cholesterol and triglyceride levels, was observed in the sera of the tested group. The levels of total cholesterol and phospholipids in the sera, as well as the concentrations of lipids in the aortic walls, showed no significant differences. The results obtained could provide evidence for the existence of an additional mechanism of silicon antiatheromatous action, concerning the modification of activity of enzymatic systems involved in lipids metabolism.     

Mercury and selenium distribution in human kidney cortex

Concentration of mercury and selenium were analyzed in tissue fractions of human kidney cortex samples from seven autopsy cases. Total mercury content ranged between 0.3–9.0 nmol Hg/g wet wt. Between 27–61% of the total mercury was found in the 105,000g supernatant of the tissue homogenate from six cases. In kidney cortex from the seventh case, a deceased dentist with the highest concentration of mercury, only 3% of the total mercury was found in the 105,000g supernatant and about 88% in a SDS-insoluble fraction. In this fraction the molar ratio between mercury and selenium was close to 1∶1. This study supports results from previous animal studies and indicates that mercury in human kidney cortex could be deposited in forms with different solubility. It could be of importance to speciate different forms of mercury in tissues according to solubility and association to selenium when interpretations of mercury concentrations are made.     

Enhancement of the kidney Cd burden by SH-containing chelating agents

The accumulation of Cd in the kidneys is enhanced markedly if chelating agents that contain SH-groups like 2,3 dimercaptopropanol (BAL) are injected immediately after the metal. This is not a transient effect but persists for more than 3 d. It is less pronounced at higher chelate doses or when the pH of urine is increased. Our experiments indicate that chelating agents, which form unstable complexes at acid pH and are able to pass through the cell membrane, will cause metal accumulation in the kidneys.     

Effect of sex and time of sampling on selenium and glutathione peroxidase activity in tissues of mature rats

Sprague-Dawley rats were used to investigate variations in measures of glutathione peroxidase (GSH-Px) and selenium (Se) concentration resulting from diurnal cycles and sex. Mature rats (equal numbers of males and females) were killed at 4 h intervals over a 48 h period (0200, 0600, 1000, 1800 and 2200 h each day). Selenium and GSH-Px were measured in plasma, erythrocytes, and liver and kidney cytosols. Selenium concentrations did not vary diurnally, but plasma GSH-Px activities were higher during the light than dark periods. Males had greater plasma GSH-Px activities and Se concentrations (42 EU and .45 mg/kg, respectively) than females (35 EU and .41 mg/kg respectively). GSH-Px activities were also higher in male kidney cytosols than females (117 and 76 EU, respectively). Selenium and GSH-Px activities, however, were lower in male liver cytosols (.48 mg/kg and 272 EU) than females (1.19 mg/kg and 795 EU, respectively). These data suggest that Se is distributed differently in male and female rats and the difference in Se distribution is accomplished by differences in GSH-Px activities.     

Intracellular distribution and chemical forms of arsenic in rabbits exposed to arsenate

Inhibition of the methylation of arsenic in rabbits by ip injection of periodate-oxidized adenosine (PAD) prior to an iv injection of⁷⁴As-arsenate (AsV; 0.4 mg As/kg body wt) caused a marked increase in the retention of⁷⁴As in both the cellular organelles and the soluble fractions of liver and kidney. One day after exposure, almost 30% of the arsenic in the liver and about 40% of the arsenic in the kidney was recovered in the nuclear fraction. In the liver nuclei, the inhibition of the methylation increased the⁷⁴As content of the insoluble fraction and most of this arsenic was protein-bound. The major part of the soluble intranuclear⁷⁴As was in the form of AsIII, formed by reduction of the administered AsV. In the liver, PAD also caused a pronounced increase in the⁷⁴As content of the microsomal fraction. In the kidneys, where most of the arsenic was present as AsV, there was a marked accumulation of arsenic in the mitochondria.     

A new technique for the study of erythrocyte survival by double labeling and use of a well-type Ge detector

A double label procedure with⁵⁷Co and⁵⁸Co has been developed for detailed in vivo studies of erythrocyte survival. A well-type Ge detector is used in the measurements. The activities necessary for these experiments are very low, and the associated dose received by the test persons can be neglected.     

Transformation of human kidney epithelial cells to tumorigenicity by nickel(II) and V-HA-RAS oncogene

Nickel is a toxic metal of environmental concern that has been found to be carcinogenic in man and animals. Primary human kidney (NHKE) cells were immortalized or rescued from senescence after exposure to NiSO₄. The cell lines (IHKE) displayed abnormal karyotype and anchorage independent growth was observed. However, none of the IHKE cells produced tumor upon injection into athymic nude mice. Transfer of the v-Ha-ras oncogene into IHKE cells induced conversion of the immortalized cells into cell lines (THKE) that were tumorigenic when transplanted into athymic nude mice. Ha-ras DNA was present in the transformed cell lines and expressed at high level.     

The involvement of heterochromatic damage in nickel-induced transformation

Nickel ions produce selective damage in heterochromatic regions of chromosomes. Male Chinese hamster embryo cells, which have heterochromatin along the entire long arm of the X-chromosome, exhibit an unusually high incidence of nickel-induced transformation compared with female cells of the same species. However, 3-methylcholanthrene, a carcinogen that produces a random distribution of chromosome damage, transforms female and male cells equally. Other species that do not have as much heterochromatin on the X-chromosome exhibit similar incidences of nickel-induced tumors in males and females. Four out of five of the male nickel-transformed Chinese hamster cell lines exhibit a deletion of the heterochromatic long arm of the X-chromosome as the only common karyotypic aberration. This result indicates that a deletion of a heterochromatic chromosomal region may be an important feature of the nickel-induced carcinogenic process. All of the male nickel transformed cells lines are able to form tumors in athymic nude mice.     

Study of correlation of se content in human hair and internal organs by INAA

The correlations of essential element Se between human hair and kidney-cortex, liver, and lung from the same subjects were investigated by instrumental neutron activation analysis, using the reaction⁷⁶Se (n, γ)^77mSe, for 24 Chinese autopsies. The concentration of Se is higher in kidney-cortex (2.04–5.36 mg/kg) than in liver (0.73–2.29), lung (0.50–1.85), and hair (0.37–1.43). It is important to know that there are significant relationships of Se concentration between hair and the other three internal organs. The correlation coefficient by linear regression analysis are 0.639, 0.570, and 0.635 for liver, lung, and kidney-cortex, respectively; and theP values are all less than 0.01 for the three tissues.     

Interaction of dietary calcium,manganese, and manganese source (Mn oxide or Mn methionine complex) on chick performance and manganese utilization

Two trials were conducted to determine the utilization of manganese (Mn) as influenced by the level and source of Mn and the level of dietary calcium (Ca) in broiler chickens. Trial One was a 2 x 2 x 3 factorial arrangement of two Mn sources (Mn methionine or manganous oxide), two levels of dietary Ca (1.8 or 1.0), and three levels of supplemental Mn (30, 60, or 200 mg/kg) fed until 4 wk of age. Total phosphorus (available phosphorus) levels were 0.70% (0.48%) during all ages. High levels of dietary Ca caused a slower early rate of growth (0.53 vs. 0.64 kg) for chicks fed 1.8 vs 1.0% Ca, respectively. Chick weight was equivalent for all diets within the Ca-treatment group, except the dietary combination of high Ca and 200 mg/kg Mn as Mn methionine. Bone and liver Mn were significantly increased as the Mn level increased, but were not affected by the Mn source. Chicks fed 1.8% Ca had higher levels of bone Mn (9.28 ppm) than chicks fed 1.0% Ca (7.23 ppm). High levels of dietary Ca and 200 ppm Mn methionine dramatically depressed early growth, feed intake, and bone ash in this trial, raising the question of a diet x environment (heat-stress) effect. Trial Two was a 2 x 2 factorial arrangement of two levels of dietary Ca (1.8 or 1.0%) and two Mn sources (200 mg/kg Mn as Mn methionine or MnO) up to 3 wk of age in a controlled heat-stress environment. No growth depression in the chicks fed high levels of Ca and Mn methionine was observed. In the presence of high levels of dietary Ca, bone Mn was significantly higher when chicks were fed the MnO source. In summary, dietary Ca did not decrease Mn utilization in these trials, and availability of Mn in Mn methionine as a source compared to MnO depended on dietary Ca levels.     

Disturbances of morphological parameters in blood of rats orally exposed to aluminum chloride

The aim of this work was to assess changes of morphological parameters in the blood of rats after oral (po) administration of aluminum (Al), in relation to the time and the administered dose. The experiment was performed on female Wistar rats. The animals were administered aluminum chloride (100 mg Al/kg) daily for 21 d. Morphological assays: red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), iron serum concentration (Fe), MCH, MCHC, absolute corrected reticulocyte count (ACRC), white blood cells (WBC), and platelet count (PLT) were estimated on d 3, 7, 14, and 21, both in the control group and in intoxicated rats. After wk 1 of aluminum administration we observed a decrease of RBC, HCT, HGB and serum iron concentration in the blood of rats. The increase of the platelet count was observed earlier than changes in other parameters. Investigation has proved that the exposure of rats to aluminum administered orally results in normocytic anemia.     

Oral and subcutaneous administration of cadmium chloride and the distribution of metallothionein and cadmium along the villus-crypt axis in rat jejunum

The route of Cd uptake influences the distribution of Cd, other metals, and metallothionein (MT). Although intestinal MT levels related to the tissue mass did not show proximodistal gradients after sc administration of CdCl₂, orally administered high doses of CdCl₂ increased mucosal MT levels longitudinally from the duodenum to the ileum. The gradient abolished when the mucosal MT level was related to the intestinal length. To further elucidate this finding, three groups of rats were studied: a control group, a group receiving dietary CdCl₂, and a group receiving sc injections of CdCl₂. The small intestine was removed after a 14-d treatment. Midjejunal segments were mounted in a cryomicrotome and cut transversally into five layers along the villus-crypt axis. Mucosal enzymes were measured to control these sections. Cd was measured by AAS and MT by RIA. Alkaline phosphatase and lactase activities exhibited the typical villus-crypt gradient. Mucosal MT levels paralleled those of Cd. Although Cd and MT concentrations were high at the tip of the villi and low in the crypts after oral administration, sc treatment reversed that profile. A molar Cd-MT ratio of approx 10 or 1 was reached after po or sc treatment, respectively. This demonstrates that only oral Cd may lead to an accumulation of Cd in the mucosal tissue fairly exceeding the binding capacity of small intestinal MT. The results show that different routes of Cd intake lead to a different MT-induction pattern in the intestinal wall and that longitudinal Cd and MT concentration gradients in the small intestine observed after high oral doses are a result of their high levels at the villus tips.     

The effect of diabetes on the molecular localization of maternal and fetal zinc and copper metalloprotein in the rat

The molecular localization of maternal and fetal zinc and copper metalloproteins in diabetic and control rats was studied. Compared to controls, liver and kidneys of diabetic dams showed an increased concentration of zinc and copper that was associated with metallothionein. In contrast, fetuses of diabetic dams had lower zinc and metallothionein levels than fetuses from controls. The abnormal maternal trace element metabolism seen with diabetes resulted in alterations of zinc uptake and/or retention of their fetuses.