Jerzy K. Piotrowski

Influence of certain metals on the level of metallothionein‐like proteins in the liver and kidneys of rats

Rats were given certain metal salts once every other day for six to eight doses and therafter the levels of metallothionein-like proteins (MTP) were determined in their liver and kidneys. The normal level of those proteins ranged from 0.1 to 0.4 mg/g in the liver and 0.2 and 0.6 mg/g in the kidney. Beryllium, magnesium, barium, strontium, tin, arsenic, selenium, chromium, and nickel administration did not influence the tissue levels of MTP. There was a tendency toward increased MTP levels in the liver after the application of high doses of iron. A significant increase in MTP levels in the liver resulted from cobalt administration and in the kidneys of bismuth-treated rats. Applying molecular filtration it was shown that both metals were partially bound in vivo to protein fractions, the molecular weights of which are close to that of metallothionein.

Hepatotoxicity of tetrabromobisphenol-A: effects of repeated dosage in rats.

Tetrabromobisphenol-A (TBBP-A) is used as a reactive flame retardant and as an intermediate in the production of other flame-retardants. In our study, TBBP-A was administered intragastrically, daily for 7 or 7-28 days at three dose levels. Significant changes of biochemical indicators were noted with regard to glutathione (GSH), malondialdehyde (MDA) and 5-aminolevulinate dehydratase (ALA-D). The level of GSH was lowered by the two higher doses (female rats only) and MDA was elevated by the highest dose (male rats only). The ALA-D activity reacted in opposite directions for both sexes. Other indicators did not yield any conclusive results. The 28-day study was performed on female rats. For GSH and MDA the medium dose resulted in a systematic increase. Insignificant changes in ALA-D activity in the liver were observed throughout the experiment. The activity of 5-aminolevulinate synthase had a decreasing tendency at 250 mg/kg of TBBP-A during the whole time of observation. Other general indices such as the activity of gamma-glutamyltransferase, concentration of microsomal proteins and the level of cytochrome P-450 did not show any significant changes. The most pronounced changes were noted with regard to indicators of porphyrogenic action. The results suggest that TBBP-A is capable of disturbing the heme metabolism in rats.

Urinary cadmium as indicator of renal cadmium in humans: an autopsy study

Objective: To estimate the equivalent cadmium levels in renal cortex and in urine, as based on autopsy analysis of subjects not exposed to cadmium occupationally. Methods: The levels of Cd were determined in renal cortex, liver, urine and urinary bladder of 39 subjects deceased at the age 42+14 years. Flame atomic absorption spectrometry (kidneys, liver) and flameless AAS (urine, bladder) were used. Results: The urinary cadmium level determined post mortem is strongly correlated with the renal Cd levels. Eliminating cases with high urinary proteins and extrapolating from sets of data with elevated urinary protein concentration to its normal range yielded a value of 1.7 mg/g creatinine as equivalent to the renal level of 50 mg/g w.w. Conclusions: It seems possible to use monitoring data for cadmium in urine and in renal cortex in a coherent way.

Inducible gold-binding proteins in rat kidneys

Abstract Repeated administration of gold (chloroauric acid) to rats resulted in a marked increase in the level of low molecular weight renal metal binding proteins (RMBP). [ 35 S]Cysteine incorporation studies pointed to an induced biosynthesis of the latter under the influence of gold. The gold-binding proteins (Au-BP) were found predominantly in the kidney cytosol, but also extracts from 12,000 g and 1000 g sediments (mitochondria and nuclei) contained low molecular weight gold complexes. The Au-BP isolated from the post-mitochondrial supernatant of rat kidneys had an apparent molecular weight of 12,000, and on DEAE-cellulose gave four fractions all containing gold. in amounts 11–33 μg Au/mg protein, and copper, above 18 μg/mg protein. The protein solutions were yellowish and their u.v.-spectra showed extinction maxima at 220–225 nm as well as slight shoulders at 250–280 nm. The Au-BP displayed a tendency for coprecipitation and aggregation. A relation of the renal Au-BP to the mercury- and bismuth-binding proteins is suggested.

Cadmium, zinc, copper and metallothionein levels in human liver.

SummaryThe concentrations of cadmium, zinc, copper and metallothionein in the autopsy samples of liver among the inhabitants of Łódź (Poland) were determined. The cadmium levels were low in the range of 1.5 to 5.8 μg/g. The concentration of metallothionein determined by the Hg-method was high (0.160–1.665 μmol Hg/g); it was mainly a Zn-thionein. The percentage of hepatic zinc bound in the MT-fraction increased with the overall content of zinc in the liver. The elevation of zinc in the liver occurs in the proportion required for the saturation of metal-binding ligands of metallothionein. The role of cadmium remains less clear. Our results suggest that the metallothionein level in the liver increase significantly in response to elevated cadmium concentrations. This response, however, is in high excess to the demand which is justified stoichiometrically.

Effect of selenium on the organ distribution and binding of bismuth in rat tissues.

Subcutaneous administration of bismuth, both single and multiple, resulted in deposition of this metal mainly in the kidneys which contained over 50% of the ‘accessible pool’ of bismuth. In the kidneys bismuth was bound mainly by the soluble fraction in which it was complexed with a protein of molecular weight of about 7000. Multiple administration of bismuth increased the level of this protein. Selenite administration brought about an increase in the ‘accessible pool’ of bismuth, probably due to a drop in excretion, and also changes in the organ distribution of this metal. The retention in the kidneys was diminished while those in the liver and in other tissues were augmented. These changes were accompanied by a change in the chemical form of bismuth present in the kidneys manifested by the total disappearance of the protein complex of molecular weight of 7000. The increased synthesis of this protein due to bismuth administration was not abolished completely.ZusammenfassungNach einmaliger und wiederholter subkutaner Verabreichung wurde Wismut zu mehr als 50% der „erreichbaren Menge” in den Nieren gefunden. Es war dort vorwiegend in der löslichen Frakion und in großem Umfang an einen Eiweißstoff vom Molekulargewicht 7000 gebunden. Bei wiederholter erabreichung von Wismut wurde auch dieser Eiweißstoff vermehrt gefunden. Die gleichzeitige Verabreichung von Selen erhöhte die „verfügbare Menge” von Wismut, wahrscheinlich wegen eingeschränkter Ausscheidung. Zugleich wurden Unterschiede in der Organverteilung von Wismut festgestellt. Der Anteil in den Nieren wirde geringer und derjenige in Leber und sonstigen. Organen größer. Der Eiweißkomplex mit dem Molekulargewicht 7000 verschwand gänzlich. Die durch Wismut stimulierte Synthese dieses Eiweißstoffes wirde aber nicht ganz verhindert.

Acute and subacute nephrotoxicity of 2-bromophenol in rats.

The present report aims at providing broader information on the acute nephrotoxicity of 2-bromophenol (2-BP) (a bromobenzene (BB) metabolite), due to its action on the kidneys, after repeated administration. Investigations were performed on female rats. Following a single dose, the most pronounced changes involved: concentrations and rates of excretion of proteins in urine, the number of epithelial cells excreted in urine, creatinine and urea clearance and reduced glutathione in renal tissue. Immediate effects could be ascribed to both renal tubules and glomeruli, mirrored in the level of urinary proteins and intensified excretion of renal epithelial cells. Less pronounced changes of the indicator values were noted under repeated dosing of 2-BP. The results obtained in a single exposure study confirm earlier reports on the mild nephrotoxicity of 2-BP following exposure to high doses. However, the transition from single to repeated exposure does not result in enhanced nephrotoxicity.

Biological levels of cadmium and zinc in the small intestine of non-occupationally exposed human subjects

The objective of this study was to estimate the relationships between cadmium (Cd) levels in the small intestine and other organs (kidney, liver, lungs) and factors influencing the intestinal Cd levels in humans, as based on autopsy analysis of subjects not exposed to Cd occupationally. The study also involved estimating the levels of zinc (Zn) in these organs, as it is known that this element exerts interactions with Cd at the level of absorption and tissue binding. The levels of Cd and Zn were determined in the renal cortex, liver, lungs and three fragments of the small intestine (duodenum, jejunum, ileum) of 29 subjects deceased at the age 42± 13 years. Flame atomic absorption spectrometry (AAS; kidneys, liver) and flameless AAS (lungs, intestine) were used. The level of Cd in the lungs was used as a marker of smoking habit. The determined levels (mean± SD) were: 0.28± 0.16 mg Cd/g and 15.2± 3.4 mg Zn/g in the duodenum; 0.26± 0.15 mg Cd/g and 16.9± 3.7 mg Zn/g in the jejunum; 0.13± 0.07 mg Cd/g and 14.6± 5.4 mg Zn/g in the ileum. Intestinal Cd levels are correlated with organ and total body Cd, and this was best expressed for Cd in ileum (r=0.67 with renal, r=0.71 with hepatic and r=0.68 with total Cd). In conclusions, the levels of Cd in the small intestine of humans are relatively low and reflect predominantly the whole body retention of this element. Somewhat higher levels of Cd are contained in the initial parts of the small intestines. In all fragments of small intestines the levels of Cd are higher in smokers. Also, the levels of Zn were relatively low and did not correlate with the levels of Cd.

Metal composition of human hepatic and renal metallothionein

This article is based on data on the levels of metals (Cd, Zn, Cu) and metallothionein (MT) determined radiochemically with203Hg in renal cortex and liver of 137 autopsy cases. From this number, for 23 cases, the gel filtration of the cytoplasmic fraction of the organs was performed.The molar content of metals in the MT fraction (Sephadex G-50) amounted to 46.9, 50.2, and 2.0% for Cd, Zn, and Cu in renal cortex, respectively, and to 8.3, 83.6, and 9.1% for Cd, Zn, and Cu in the liver, respectively. In parallel with the increase of Cd and MT in renal cortex, increasing saturation was found of the MT fraction by Cd, occurring at the expense of Zn and Cu. Equimolar amounts of Cd and Zn in the MT fraction are found at Cd level of 0.5 μmol Cd/g wet wt of renal cortex. In the liver, analogous dependency (elevation of %Zn, depression of %Cd and %Cu) were observed in relation to Zn and MT levels in this organ.The basic level of Zn (not bound with MT) was estimated at 0.5 μmol/g for both renal cortex and liver. A deficit of non-MT Zn in kidneys is proposed as an alternative mechanism of toxic Cd action.

Cadmium, zinc, copper, and metallothionein levels in the kidney and liver of inhabitants of Upper Silesia (Poland)

SummaryThe levels of Cd, Zn, Cu and metallothionein (MT) were determined in renal cortex and liver of 75 subjects deceased in the period 1986–1989 in the area of Upper Silesia (Katowice). The mean age of the population studied was 53.6 ± 14.6 years. The determined levels (mean ± SD) were: 43.1 ± 23.5 μg Cd/g; 52.5 ± 17.4 μg Zn/g; 2.2 ± 0.7 μg Cu/g; 0.80 ± 0.36 μmol Hg/g in renal cortex and 3.5 ±2.5 pg Cd/g; 82.8 ± 34.3 μg Zn/g; 4.5 ± 2.6 μg Cu/g; 0.69 ± 0.44 pmol Hg/g in the liver. The level of Cd in renal cortex was 40% higher in smokers compared to nonsmokers and was independent of the gender. Whole-body retention of Cd was 34.1 ± 18.5 mg; smoking elevated the value from 27.1 to 38.2 mg. Compared with a similar study made in central Poland (Łódź), a significant difference was found only regarding the level of Zn and MT in the liver, pointing to the possibility that exposure to this element in the region of Upper Silesia may be higher.