Effects of metals on enzyme activity in plants

Abstract. Uptake of phytotoxic amounts of metal by higher plants or algae can result in inhibition of several enzymes, and in increase in activity (= induction) of others. Two mechanisms of enzyme inhibition predominate: (1) binding of the metal to sulphydryl groups, involved in the catalytic actionor structural integrity of enzymes, and (2) deficiency of an essential metal in metalloproteins or metal-protein complexes, eventually combined with substitution of the toxic metal for the deficient element. Metal accumulation in the cellular compartment of the enzyme is a prerequisite for enzyme inhibition in vivo. The induction of some enzymes is considered to play a significant role in the stress metabolism, induced by metal phytotoxicity. Peroxidase induction is likely to be related to oxidative reactions at the biomembrane; several enzymes of the intermediary metabolism might be stimulated to compensate for metal-sensitive photosynthetic reactions. The induction of enzymes and metal-specific changes in isoperoxidase pattern can be used as diagnostic criteria to evaluate the phytotoxicity of soils, contaminated by several metals. Lines for future research on metal phytotoxicity are proposed, involving the study of inhibition and induction of enzymes at the different cell membranes (especially the plasmamembrane) in vivo.     

Effects of copper aspirinate and aspirin on tissue copper,zinc, and iron concentrations following chronic oral treatment in the adjuvant arthritic rat

Concentrations of copper, zinc, and iron were analyzed and compared in a number of tissues of adjuvant arthritic rats following 22 d of chronic treatment (per os) with either vehicle, aspirin or copper aspirinate, at doses of 100 mg/kg, 200 mg/kg, or 400 mg/kg. Such chronic treatment resulted in a negative balance in copper, zinc, and iron in many tissues. Among the tissues examined, liver and kidney exhibited the greatest changes in metal concentrations; brain and skeletal muscle exhibited the least. Arthritis-induced changes in the concentrations of all three metals in the liver were reversed upon treatment with aspirin. Treatment with copper aspirinate, on the other hand, resulted in an extremely high accumulation of copper in the liver. Arthritis-induced changes in copper, zinc, and iron concentrations in the pancreas and copper concentration in the plasma were generally not reversed upon treatment with either aspirin or copper aspirinate. Among the three metals examined, the degree of change observed as a result of drug treatments was greatest for iron and least for zinc. Finally, it appeared that the effects of aspirin and copper aspirinate on tissue metal concentrations were independent of the antiarthritic effects of these compounds.     

Nystatin affects zinc uptake in human fibroblasts

The mechanism(s) by which zinc is transported into cells has not been identified. Since zinc uptake is inhibited by reducing the temperature, zinc uptake may depend on the movement of plasma membrane micoenvironments, such as endocytosis or potocytosis. We investigated the potential role of potocytosis in cellular zinc uptake by incubating normal and acrodermatitis enteropathica fibroblasts with nystatin, a sterol-binding drug previously shown to inhibit potocytosis. Zinc uptake was determined during initial rates of uptake (10 min) following incubation of the fibroblasts in 50 μg nystatin/mL or 0.1% dimethyl-sulfoxide for 10 min at 37°C. The cells were then incubated with 1 to 30 μM ⁶⁵zinc. Michaelis-Menten kinetics were observed for zinc uptake. Nystatin inhibited zinc uptake in both the normal and AE fibroblasts. Reduced cellular uptake of zinc was associated with its internalization, not its external binding. In normal fibroblasts, nystatin significantly reduced theK _m 56% and theV _max 69%. In the AE fibroblasts, nystatin treatment significantly reduced theV _max 59%, but did not significantly affect theK _m. The AE mutation alone affected theV _max for cellular zinc uptake. The control AE fibroblasts exhibited a 40% reduction inV _max compared to control normal fibroblasts. We conclude that nystatin exerts its effect on zinc uptake by reducing the velocity at which zinc traverses the cell membrane, possibly through potocytosis. Furthermore, the AE mutation also effects zinc transport by reducing zinc transport.     

Selenium,zinc, and thyroid hormones in healthy subjects

Iodothyronine 5′ deiodinase, which is mainly responsible for peripheral T₃ production, has recently been demonstrated to be a selenium (Se)-containing enzyme. The structure of nuclear thyroid hormone receptors contains Zinc (Zn) ions, crucial for the functional properties of the protein. In the elderly, reduced peripheral conversion of T₄ to T₃ with a lower T₃/T₄ ratio and overt hypothyroidism are frequently observed. We measured serum Se and RBC GSH-Px (as indices of Se status), circulating and RBC Zinc (as indices of Zn status), thyroid hormones and TSH in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid under- or malnutrition conditions, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. Low T₃/T₄ ratios and reduced Se and RBC GSH-Px activity were observed only in the older group. A highly significant linear correlation between the T₃/T₄ ratio and indices of Se status was observed in the older group of subjects (r=0.54;p<0.002, for Se;r=0.50;p<0.002, for RBC GSH-Px). Indices of Zn status did not correlate with thyroid hormones, but RBC Zn was decreased in older as compared with younger subjects. We concluded that reduced peripheral T₄ conversion is related to impaired Se status in the elderly.     

A case-control study on selenium,zinc, and copper in plasma and hair of subjects affected by breast and lung cancer

The purpose of our study was to investigate the relationship between plasma and hair levels of Se, Zn, and Cu, and cancer. We selected a total of 66 patients affected by either breast (38) or lung (28) cancer. They entered into the study at the onset of disease, and before any chemical or radiotherapy. Controls were randomly selected among healthy people and were matched for sex, age, smoking habits, and residence. In the group of breast cancer, a significant decrease in hair Se was found compared to controls (p<0.01), whereas plasma Se was only slightly decreased. No difference between cases and controls was detected in both hair and plasma levels of Zn and Cu. Subjects who developed lung cancer were significantly lower in hair Zn (p<0.05) and Cu (p<0.01) than controls, whereas there was no difference with regard to Se. In addition, plasma Cu of these patients was increased as compared to controls.     

Effects of different levels of dietary zinc on the gilthead,Sparus aurata during the growing season

Gilthead were fed three diets. Diet A was the control diet, whereas diets B and C were supplemented with 300 and 900 mg Zn/kg, respectively. Fish fed with diet C, at the end of the experiment, showed the lowest weight. Zinc concentrations presented the higher values in gills, liver, and kidney. Muscle and brain had the lower mean values and showed a tight control of zinc levels. These results reinforce the hypothesis that zinc in the CNS should be strictly controlled in order to maintain the functional role of the metal. Significant differences in tissue zinc concentrations were obtained between fish fed different amounts of zinc, the metal concentrations being higher in tissues of fish fed diet C. The tissue decrease of zinc, found at the end of the experiment, may depend on a lower feed consumption or on different zinc requirements during the cold season. These changes, even if not univocal among the three diets, may be associated with the life cycle of fish. Furthermore, copper concentrations were little affected by the different concentrations of zinc in the three diets; liver and kidney presented the highest concentrations; liver showed a significant decrease in copper content at the end of the experiment. We conclude that: zinc concentrations of the diet may affect the gilthead weights and the tissual metal content; and zinc concentrations in the diets, depending on the growth rate, may be varied depending on the season.     

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.     

Toxicity to alveolar macrophages in rats following parenteral injection of mercuric chloride

Alveolar macrophages collected by pulmonary lavage from male Fisher-344 rats at intervals (24–72 h) after HgCl₂ injection (1–5 mg/kg, sc) were analyzed by several techniques. Within 24–72 h, the macrophages showed morphological signs of activation (hypertrophy and ruffled plasma membrane). Lipid peroxidation (increased malondialdehyde concentration) was not detected until 48 h. Dose- and time-related effects of HgCl₂ on malondialdehyde concentration and time-related effects of HgCl₂ on malondialdehyde concentration and mercury content of alveolar macrophages were observed 24–72 h postinjection. Diminished cell viability occurred only at 72 h after the highest dosage of HgCl₂. This study demonstrates that the alveolar macrophage was a cellular target for mercury toxicity following parenteral exposure to HgCl₂.