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Biomedical subjects

M Nordberg

Publications and source records attributed to M Nordberg.

At least 109 records · Page 6Linked to original sources
PubMed1989

Dental amalgam and mercury.

Mercury concentration in intraoral air and urine of seven females with dental amalgam was measured before and after intake of one hard-boiled egg. A considerable decrease in mercury concentration in intraoral air was found. Twenty women with about equal dental amalgam status, with or without subjective symptoms related to dental amalgam, were also studied. Mercury concentrations in intraoral air and urine were measured. For all the 27 women the basal intraoral air concentration of mercury ranged over 0.6-10.4 micrograms/m3 (median value 4.3 micrograms/m3). This corresponds to a release of 0.02-0.38 ng/s (median value 0.16 ng/s). In urine, the mercury concentration varied from less than 0.8-6.9 micrograms/g creatinine (median value 1.9 microgram/g creatinine). Data from both parameters were significantly correlated to the total number of teeth areas with dental amalgam. Protein values in urine indicated no renal damage. Maximum concentrations of mercury vapour in intraoral air for the 27 women who had chewed chewing gum for 5 min varied between 2-60 micrograms Hg/m3 (median value 19 micrograms Hg/m3). This corresponds to 0.07-2.20 ng Hg/s and a median value of 0.70 ng Hg/s.

Adult↗
PubMed1987

Different binding forms of cadmium--implications for distribution and toxicity.

Our present understanding of mechanisms for induction of renal tubular damage by cadmium is summarized in Fig 1: Cadmium is taken up from various exposure routes into plasma where it is initially bound to albumin. Such cadmium is mainly taken up by the liver where it induces the synthesis of metallothionein, which is mainly kept intracellularly, but a small proportion escapes into blood plasma. Cadmium bound to metallothionein in plasma is quickly transported to the kidney tubule by glomerular filtration and subsequent uptake by pinocytosis into renal lysosomes. Uptake of cadmium bound to low mol. wt protein from hemolyzed blood cells may also contribute to cadmium accumulation in the renal tubule. Cadmium is released from metallothionein in the renal lysosomes, where proteins are catabolized. Non-metallothionein bound cadmium may then interact with sensitive sites in the renal cell and cause renal tubular damage. There is an internal synthesis of metallothionein in the renal cells and a balance is thus formed between metallothionein bound cadmium and non-metallothionein bound cadmium. Only in such situations when non-metallothionein bound cadmium reaches a sufficient concentration does the renal damage appear. This scheme has been based mainly on observations in animals and cellular systems. It is probable that similar conditions occur in humans; however, the amount of human evidence available to quantify the different pathways is limited. Nevertheless, based on several assumptions, a quantitative model has been designed for humans concerning relationships between exposure and development of renal damage. Available data have been summarized in two chapters of a recent publication (Nordberg et al 1985, Kjellström and Nordberg 1985). Much more data on humans would be desirable to make this kind of extrapolation with confidence.

Air↗
PubMed1987

On the role of metallothionein in cadmium induced renal toxicity.

Metallothionein plays an important role in the metabolism and toxicity of cadmium. Human beings are exposed to increasing amounts of cadmium. The critical organ in long term cadmium exposure is the kidney. Some groups in the population fall within the risk zone for developing renal tubular dysfunction from cadmium exposure. After absorption, cadmium is to a large extent distributed to the liver where it is bound to and induces the synthesis of metallothionein. Subsequently metallothionein-bound cadmium is slowly released into blood and efficiently taken up by renal tubular cells after glomerular filtration. The biological half-time of cadmium in the human kidney is considered to be very long: 10-15 years and this explains the life-long accumulation of cadmium, reaching a toxic concentration of approximately 200 ug/g in excessively exposed individuals. Human adult renal metallothionein has a natural content of cadmium which also induces the resynthesis of this protein upon its catabolism. This could be one explanation of the long biological half-time which has been reported for cadmium. Injection of metallothionein-bound cadmium can induce renal tubular kidney dysfunction at lower renal cadmium concentrations (10-20 ug/g), probably because of the fast catabolism and relatively slow synthesis of metallothionein in renal cells. A model of these and other mechanisms causing tubular kidney damage in cadmium exposure is presented.

Animals↗
PubMed1987

Cadmium, zinc, and copper in rabbit kidney metallothionein--relation to kidney toxicity.

Twenty-two rabbits were given repeated subcutaneous injection of cadmium chloride. The cumulative cadmium dose given ranged from 13 to 214 mumole/kg body weight. Five rabbits served as controls. The treatment resulted in cadmium concentrations in kidney cortex that ranged from 0.3 to 3.2 mmole Cd/kg and a subsequent production of metallothionein. The molar ratio of cadmium, zinc, and copper in metallothionein fractions from kidneys with different concentrations of cadmium was determined. At low concentrations of cadmium in rabbit kidneys, zinc was the dominating metal bound to metallothionein (70-90%). At high concentrations of cadmium in kidneys, cadmium was the dominating metal in metallothionein. Evidence of kidney toxicity, in the form of beta2-microglobulinuria, was seen when cadmium constituted 85% of the metal ions recovered from metallothionein fractions. The remaining 15% was zinc. This indicates that at most six of the seven metal-binding sites in mammalian metallothionein are occupied by cadmium and that the remaining site is occupied by zinc. Our data provide further support for the hypothesis that chronic cadmium nephrotoxicity develops when there is a lack of metal-binding sites available for cadmium in metallothionein.

Animals↗
PubMed1987

Influence of cadmium-metallothionein pretreatment on tolerance of rat kidney cortical cells to cadmium toxicity in vitro and in vivo.

Kidney cells were isolated from rats pretreated by daily subcutaneous doses of cadmium metallothionein (CdMT: 0.05-0.2 mg Cd/kg X 5) and from non-pretreated rats. Upon exposure to CdCl2 in vitro (0-200 micrograms Cd/ml), a concentration dependent decrease in viability was observed in the non-pretreated cells, while no such decrease occurred in the pretreated cells indicating that these cells were more resistant to the toxic action of cadmium. There was a higher in vitro uptake of Cd+2 and an increased metallothionein (MT) concentration in the pretreated cells (compared to non-pretreated cells). Subcellular distribution studies revealed that Cd was mainly recovered in the "cytosol" fraction. The higher total cadmium uptake in pretreated cells corresponded to an increase of Cd in "cytosol" and "nuclear" fractions. This observation may be explained by MT-binding of Cd in the cells and is in accordance with a possible protective effect of induced MT in the pretreated cells. In order to assess whether pretreatment-induced tolerance to cadmium toxicity--indicated by the cellular studies--could also be observed in vivo, some whole animal experiments were also performed. A dose-related proteinuria was observed in non-pretreated rats after a single subcutaneous administration of 109Cd-MT at doses of 0.05 and 0.4 mg Cd/kg. Urinary total Cd, 109Cd and MT was also increased in a dose-related fashion. Cadmium concentrations in kidney were dose related and reached 19 micrograms/g wet weight. In contrast, in animals repeatedly pretreated with CdMT according to 1), no proteinuria was observed after administration of the same single doses of 109CdMT. Total Cd. 109Cd and particularly MT-concentrations in urine were lower in such pretreated animals than in in non-pretreated ones in spite of the accumulation of higher tissue concentrations of total Cd (up to 80 micrograms/g). The pretreatment was thus shown to prevent some of the acute nephrotoxicity of CdMT, possibly by means of induction of MT synthesis.

Animals↗
PubMed1987

Resistance to acute nephrotoxicity induced by cadmium-metallothionein dependence on pretreatment with cadmium chloride.

Three groups of rats (B-D) were given various daily doses of CdCl2 (0.5-2 mg Cd/kg) continuously or in intervals during time periods of 1-8 weeks. Another group of animals (A) were kept untreated. At the end of the period, selected subgroups of groups A-D were given a single subcutaneous injection of 109Cd-metallothionein (109CdMT) 0.05 or 0.4 mg Cd/kg ("challenge dose"). Subsequently, urinary creatinine, protein, Cd, 109Cd and MT and kidney cortex Cd, 109Cd and MT were determined. In group A (no long term pretreatment), an increased proteinuria was observed after the rats had received the lower of the challenge doses of 109CdMT, and an even greater increase after the higher challenge dose of 109CdMT. No such increase appeared in group B, C and D (repeatedly pretreated with CdCl2) at either of the challenge doses. Higher metallothionein concentrations in kidney cortex observed in the pretreated groups constitute a plausible explanation of the protective effects of pretreatment against the development of increased proteinuria after challenge dosing. It is likely that increasing Cd concentrations, gradually accumulating in the renal cortex (22-226 micrograms/g wet wt.) as a result of the pretreatment, served to induce the synthesis of metallothionein in the renal cortical cells, thus making them resistant to the challenge from 109CdMT.

Acute Disease↗
PubMed1986

Uptake of cadmium in isolated kidney cells--influence of binding form and in vivo pretreatment.

Uptake of cadmium as 109CdCl2, 109Cd-cysteine, 109Cd-albumin and 109Cd-metallothionein was studied in isolated kidney cells from rat. Cd as 109CdCl2 and 109Cd-albumin was taken up at similar rates. The uptake of cadmium as 109Cd-cysteine was greater and that of 109Cd-metallothionein lower compared with that of the other substances. These observations were made on non-pretreated cells. In cells taken from rats pretreated with CdCl2 in vivo, the uptake of cadmium as 109CdCl2, 109Cd-cysteine and 109Cd-albumin was lower than in cells from non-pretreated rats. However, the uptake of 109Cd-metallothionein was considerably enhanced in pretreated cells. In pretreated kidney cells the decreased uptake of Cd (as Cd-albumin) might be related to protection of the kidney against acute Cd toxicity and increased uptake of metallothionein-Cd might contribute to the explanation of renal damage in long-term Cd exposure.

Albumins↗