G.B. van der Voet

Arsenic-induced toxicity: effect on protein composition in sciatic nerve

Exposure to arsenic compounds may lead to skin and lung cancer and various disorders such as vascular disease and peripheral neuropathy in humans. Peripheral arsenic neurotoxicity has been demonstrated clinically and in electrophysiological studies. Patients intoxicated with arsenic show neurological symptoms in their feet and hands. These patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison with controls. The mechanism of arsenic peripheral nervous system (PNS) toxicity, however, has never been described before. This is the first study to investigate the toxicity of arsenic on the PNS. Male Wistar rats were exposed to arsenite given as a single dose i.v. After sacrifice, sciatic nerves were excised and the protein composition was analysed. Protein analysis of sciatic nerves showed disappearance of neurofilament and fibroblast proteins in rats treated with arsenite doses of 15 and 20 mg/kg in comparison with the control groups. Some fibroblast protein bands had disappeared in the 20-mg/kg dose group. The analysed neurofilament-M and-L proteins decreased dose dependency over time. arsenic affects the composition of proteins in the rat sciatic nerve, especially the neurofilaments. The reduction of signals in Western blot analysis reveals changes in cytoskeletal composition, which may well lead to neurotoxic effects in vivo.

Distribution of Aluminium between Plasma and Erythrocytes

It is common use to monitor body burdens of toxic trace metals by measuring concentrations in whole blood. To monitor aluminium (Al) body burden in renal patients on haemodialysis, which is a high-risk group for Al poisoning, the concentrations of Al in plasma (AlP) or serum (AlS) are determined rather than Al in whole blood (AlB). To evaluate this custom, which exists in clinical laboratories, an investigation was made into the distribution of Al between the plasma and the blood-cell compartment and on the extent of binding of Al to the blood cells both in rats and in dialysed patients. The results show that Al is distributed between plasma and blood cells with only very small quantitative differences, that binding of Al to blood cells is very weak and that AlP and AlB have similar prognostic value for toxicity.1 It is common use to monitor body burdens of toxic trace metals by measuring concentrations in whole blood. To monitor aluminium (Al) body burden in renal patients on haemodialysis, which is a high-risk group for Al poisoning, the concentrations of Al in plasma (AIP) or serum (AlS) are determined rather than Al in whole blood (AlB).2 To evaluate this custom, which exists in clinical laboratories, an investigation was made into the distribution of Al between the plasma and the blood-cell compartment and on the extent of binding of Al to the blood cells both in rats and in dialysed patients.3 The results show that Al is distributed between plasma and blood cells with only very small quantitative differences, that binding of Al to blood cells is very weak and that AlP and AIB have similar prognostic value for toxicity.

Intestinal absorption of aluminium: effect of sodium and calcium

Abstract Aluminium (Al) is recognized as a toxin in patients with deficient renal function. Moreover, Al may play a role in some neurodegenerative diseases. It is hypothesized that more than one intestinal absorption mechanism exists for Al, related to various intraluminal chemical species, and that Al shares intestinal transport routes for essential inorganic substances due to similarities in their chemical speciation characteristics. The purpose of the present investigation was to study the ef-fects of ionic Na (0–120 mmol/l) and Ca (0–10 mmol/l), alone and in combination, on the intestinal absorption of ionic Al (20 and 30 mmol/l). A previously standardized method of perfusion of rat small intestine was used, combined with serial blood sampling. Mucosal uptake and systemic appearance of Al in the blood were monitored during 1 h perfusion, together with Na and Ca; the metals were given as the chloride. The intestinal absorption of Na and Ca was taking place according to previously reported mechanisms. A one-sided negative interaction was shown to exist between Ca and Al resp. Al and Na during both mucosal uptake and systemic appearance; Ca interacts negatively with Na during systemic appearance, but enhances mucosal uptake of Na. It may be speculated that Al mimicks Ca in its Na-dependent intestinal passage.Aluminium (Al) is recognized as a toxin in patients with deficient renal function. Moreover, Al may play a role in some neurodegenerative diseases. It is hypothesized that more than one intestinal absorption mechanism exists for Al, related to various intraluminal chemical species, and that Al shares intestinal transport routes for essential inorganic substances due to similarities in their chemical speciation characteristics. The purpose of the present investigation was to study the ef-fects of ionic Na (0–120 mmol/l) and Ca (0–10 mmol/l), alone and in combination, on the intestinal absorption of ionic Al (20 and 30 mmol/l). A previously standardized method of perfusion of rat small intestine was used, combined with serial blood sampling. Mucosal uptake and systemic appearance of Al in the blood were monitored during 1 h perfusion, together with Na and Ca; the metals were given as the chloride. The intestinal absorption of Na and Ca was taking place according to previously reported mechanisms. A one-sided negative interaction was shown to exist between Ca and Al resp. Al and Na during both mucosal uptake and systemic appearance; Ca interacts negatively with Na during systemic appearance, but enhances mucosal uptake of Na. It may be speculated that Al mimicks Ca in its Na-dependent intestinal passage.

Aluminium Binding to Serum Constituents: A Role for Transferrin and for Citrate

The binding of aluminium in rat serum was studied. Rats were loaded intraperitoneally with different doses of aluminium(III)chloride 4 times during one week, before being killed by cardiac puncture. One ml of serum was applied to a Sephacryl S-200 SF column and 70 fractions were collected. In the collected fractions, the distribution of aluminium was measured and compared with the concentrations of total protein, transferrin, and citrate. The presence of a high molecular weight aluminium-complex in serum is confirmed. Although a possible role for albumin cannot be excluded, it is most likely that transferrin plays a role as a carrier for biological transport of aluminium in plasma. In addition to transferrin, aluminium was shown to be associated with citrate in serum, resulting in a low-molecular weight complex. It is postulated that citrate acts as a chelator for aluminium, and that the Al/citrate complex in serum may play an important role in intracellular accumulation, and hence the toxicity, of aluminium.

Intestinal Absorption of Aluminium in Rats: Effect of Sodium

Aluminium (Al) is no longer known as a non-toxic element. Al is the cause of several dialysis-related diseases (microcytic anaemia, vitamin D-resistant osteomalacia, dialysis encephalopathy) and plays a possible role in various other disorders (Alzheimer’s disease, amyotrophic lateral sclerosis) (Flendrig et al. 1976; Alfrey et al. 1976; Wills and Savory 1983). The Al uptake from the intestine may be one of the main sources of Al in the body and, therefore, of Al toxicity, especially in renal patients on oral Al hydroxide therapy (Clarkson et al. 1972; Cam et al. 1980; Griswold et al. 1983; Randall 1983; Kaye 1983; Cannata et al. 1983a).

Intestinal Absorption of Aluminium in Rats

To study the mechanism of intestinal aluminium (Al) absorption, an experimental investigation into the uptake of Al from the rat gut was undertaken. The small intestine was perfused in situ for 60 min with isotonic media containing 4.63, 9.25, and 18.50 mmol/l Al chloride at pH 4.0 and 7.0. Portal and systemic blood were sampled and analysed for its Al content by flameless atomic absorption spectrophotometry. It was found that the intestinal absorption of Al in rats is concentration and pH dependent.

Renal damage in mice after sequential cisplatin and irradiation: the influence of prior irradiation on platinum elimination

Doses of 4-6 mg kg-1 c-DDP given 6 months before renal irradiation caused only a modest increase in functional radiation damage (DEF 1.1). These effects could be explained by additive toxicities and the damage was much less than when c-DDP was given 3-6 months after irradiation. Pharmacokinetic studies did not demonstrate any decrease in the rate of platinum elimination after previous low-dose renal irradiation.

Serum Aluminium Concentrations in Patients with Rheumatoid Arthritis

Aluminium (AlS) and zinc (ZnS) concentrations in serum were measured in patients with rheumatoid arthritis (RA) with and without Al-containing drugs and compared with levels in healthy controls. In RA patients without Al-containing antacids, the AlS levels did not differ from those of the healthy controls (mean 9.9, SEM 0.9 microgram/l and mean 8.6, SEM 0.5 microgram/l). However, the AlS levels in RA patients treated with Al-containing drugs were significantly (p less than 0.05) higher than in the other two groups (mean 14.1, SEM 1.1 microgram/l). Serum zinc (ZnS) levels in both RA groups were significantly (0.01 less than p less than 0.025) lower than in the healthy controls (mean 10.5, SEM 0.4 mumol/l and mean 10.2, SEM 0.4 mumol/l for the RA groups with and without Al-containing drugs, and in healthy volunteers mean 14.4, SEM 0.6 mumol/l). The difference in AlS levels might be due not only to the intestinal absorption of Al from Al-containing drugs, but also to a slightly impaired renal function, serum creatinine being slightly but significantly higher (p less than 0.05) in the Al-treated RA group than in non-Al-treated one. This difference in serum creatinine between the two RA groups might be explained by the more frequent use of cimetidine in the Al-treated RA group.