A mild magnesium deprivation affects calcium excretion but not bone strength and shape, including changes induced by nickel deprivation, in the rat.

An experiment was performed to determine the effect of a mild magnesium deprivation on calcium metabolism and bone composition, shape, and strength in rats, and whether nickel deprivation exacerbated or alleviated any changes caused by the magnesium deprivation. Weanling male rats were assigned to groups of 10 in a factorial arrangement, with variables being supplemental nickel at 0 and 1 mg/kg and magnesium at 250 and 500 mg/kg of diet. The basal diet contained about 30 ng Ni/g. Urine was collected for 24 h during wk 8 and 12, and rats were euthanized 13 wk after dietary treatments began. Mild magnesium deprivation decreased the urinary excretion of calcium and increased the tibia concentration of calcium but did not affect femur shape or strength (measured by a three-point bending test). Dietary nickel did not alter these effects of magnesium deficiency. Nickel deprivation increased the urinary excretion of phosphorus and the femur strength variables maximum force and moment of inertia. Strength differences might have been the result of changes in bone shape. Magnesium deprivation did not alter the effects of nickel deprivation on bone. The findings indicate that a mild magnesium deficiency affects calcium metabolism but that this does not markedly affect bone strength or shape, and these effects are not modified by dietary nickel. Also, nickel deprivation affects phosphorus metabolism and bone strength and shape; these effects apparently are not caused by changes in magnesium metabolism or utilization.

Interactions between essential trace and ultratrace elements.

Fully crossed, factorially arranged experiments showed that, under defined conditions, interactions occur between nickel and iron, nickel and copper, arsenic and zinc, and possibly vanadium and chromium. Nickel and iron interacted when dietary iron was supplemented as ferric sulfate only. Signs of nickel deprivation were more severe when dietary iron was low; or the signs of moderate iron deficiency were more severe when dietary nickel was deficient. When iron was supplemented to the diet as a 60% ferric-40% ferrous sulfate mixture, nickel and iron apparently did not interact. The findings suggested a synergistic relationship between nickel and iron when dietary iron was in a relatively unavailable form. An antagonistic interaction between nickel and copper was found when dietary iron was supplemented as a 60% ferric-40% ferrous sulfate mixture. Signs of copper deficiency were more severe in nickel-supplemented than in nickel-deprived rats. When the rats were made severely iron deficient by feeding of low levels of ferric sulfate only, no apparent interaction between nickel and copper was found. The interaction between arsenic and zinc apparently was noncompetitive. When dietary zinc was 40 microgram/g, arsenic-deprived chicks exhibited depressed growth and elevated hematocrits. In zinc deficiency, growth was more markedly depressed and hematocrits more markedly elevated in arsenic-supplemented than in arsenic-deficient chicks. Arsenic might be necessary for the efficient utilization or metabolism of zinc. Findings indicating an interaction between vanadium and chromium were tentative. In one experiment, the addition of 500 microgram of chromium/g of diet apparently made 5 micrograms of vanadium/g of diet toxic for chicks. Thus, the interactions between essential trace and ultratrace elements might be of nutritional significance.

[Activity of proteases, leucine arylamidase and alpha-amylase in pancreatic tissue during nickel deficiency]. / Zur Aktivität der Proteasen, Leucinarylamidase und alpha-Amylase im Pankreasgewebe bei Nickelmangel.

In studies on the essentiality of nickel, important differences of enzyme activities and also of substrates were established. The results of the present paper show that these changes cannot be explained by a lowered reduction of dietary proteins, since the activity of the proteases rather increased during Ni deficiency. However, the digestion of the starch by alpha-amylase, being 57% lower, could have been partially responsible for the large differences in the activities of the hepatic enzymes and in the concentrations of the hepatic metabolites and also in the weight gains.

Nickel deficiency alters nickel flux in rat everted intestinal sacs.

This study was conducted to determine nickel absorption in nickel-deficient rats. Jejunal segments obtained from dietary nickel-depleted (13 microg nickel/kg diet) and nickel-control (1 mg nickel/kg diet) adult rats from the first generation, and suckling pups from the second offspring were used. The nickel transfer across the intestinal epithelium and nickel uptake into the intestine were measured by use of everted jejunal sacs using a wide range of nickel concentrations administered on the luminal side (1.1 x 10(-8) M til 1.0 x 10(-4) M). Both the intestinal nickel transfer and nickel uptake were influenced by the dietary nickel supply in rat offspring, but not in the adult rats from the first generation. However, in nickel-deficient offspring, the nickel transfer across the small intestine was higher than in nickel-control offspring. This difference was greater using low intraluminal nickel concentrations than high nickel concentrations, and was significant at 1.1 x 10(-8) M, 6.1 x 10(-8) M, 5.1 x 10(-7) M, 1.0 x 10(-6) M, and 5.0 x 10(-6) M. Also, nickel uptake into the intestine was somewhat greater in nickel-deficient rat pups than in nickel-control pups, and significant using 1.1 x 10(-7) M and 1.0 x 10(-6) M nickel. A definite saturation type kinetic for the intestinal nickel absorption in relation to the intraluminal nickel concentration could not be observed.

Dietary vitamin B12, sulfur amino acids, and odd-chain fatty acids affect the responses of rats to nickel deprivation.

An experiment was performed to ascertain whether changing the dietary intake of two substances, cystine and margaric acid (heptadecanoic acid), that affect the flux through pathways involving the two vitamin B12-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, would affect the interaction between nickel and vitamin B12. Rats were assigned to treatment groups of six in a fully crossed, four-factorial arrangement. The independent variables, or factors, were: per kg of fresh diet, nickel analyzed at 25 and 850 micrograms; vitamin B12 supplements of 0 and 50 micrograms; margaric acid supplements of 0 and 5 g; and L-cystine supplements of 0 and 12 g. The diet without cystine was marginally deficient in sulfur amino acids. Nickel affected growth, liver wt/body wt ratio (LB/BW), and a number of variables associated with iron, calcium, zinc, copper, and magnesium metabolism. Most of the effects of nickel were modified by the vitamin B12 status of the rat. In numerous cases, the interaction between nickel and vitamin B12 was dependent on, or altered by, the cystine or margaric acid content of the diet. Thus, the findings showed that the extent and the direction of changes in numerous variables in response to nickel deprivation varied greatly with changes in diet composition. These variables include those previously reported to be affected by nickel deprivation, including growth and the distribution or functioning of iron, calcium, zinc, copper, and magnesium. The findings also support the hypothesis that nickel has a biological function in a metabolic pathway in which vitamin B12 is important.

Nickel deficiency diminishes sperm quantity and movement in rats.

Early studies on nickel essentiality with rats and goats indicated that nickel deprivation impaired reproductive performance. Nickel also has been found to influence cyclic nucleotide gated channels (CNG); these types of channels are important in sperm physiology. Thus, two experiments were conducted to test the hypothesis that nickel deficiency affects sperm physiology in a manner consistent with nickel having an essential function related to CNG channel functions. The experiments were factorially arranged with four treatment groups of eight weanling rats in each. In experiment 1, the treatments were supplemental dietary nickel of 0 and 1 mg/kg and N(omega)-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) added to the drinking water (50 mg/100 mL) the last 3 wk of an 8-wk experiment. In experiment 2, the treatments were supplemental dietary nickel at 0 and 1 mg/kg and supplemental dietary sodium chloride (NaCl) at 0 and 80 g/kg. The NaCl and L-NAME variables were included to act as stressors affecting CNG channel activity. The basal diet contained per kilogram about 27 microg of nickel and 1 g of sodium. After 8 wk in experiment 1 and 16 wk in experiment 2, urine while fasting and testes and epididymis in both experiments, and seminal vesicles and prostates in experiment 2 were harvested for analysis. Nickel deprivation significantly decreased spermatozoa motility and density in the epididymides, epididymal transit time of spermatozoa, and testes sperm production rate. Nickel deficiency also significantly decreased the weights of the seminal vesicles and prostate glands. Excessive NaCl had no effect on sperm physiology; however, it decreased prostate gland weights. The findings support the hypothesis that nickel has an essential function that possibly could affect reproductive performance in higher animals, perhaps through affecting a CNG channel function.

Effect of nitrous oxide on nickel deprivation in rats.

Because nickel may have a biological function in a pathway in which vitamin B12 is important, an experiment was performed to determine the effects of nitrous oxide exposure in rats deprived of nickel. Exposure to nitrous oxide (N2O) causes inactivation of cobalamin and a subsequent decrease in the vitamin B12-dependent enzymes methionine synthase and methylmalonyl CoA mutase. Rats were assigned to dietary groups of 12 in a factorially arranged experiment with dietary variables of nickel (0 or 1 microgram/g) and vitamin B12 (0 or 50 ng/g). After 6 wk, one-half of the rats from each dietary group were exposed to 50% N2O/50% O2 for 90 min/d for the last 28 d of the experiment. Vitamin B12, N2O, or their interaction had numerous effects; classical findings included N2O-induced reduction in plasma vitamin B12 and decreases in the vitamin B12-dependent enzymes. Inactivation of vitamin B12 by N2O, however, did not exacerbate signs of nickel deprivation, possibly because the rats were able to metabolically compensate to N2O exposure.

Dietary folate affects the response of rats to nickel deprivation.

Because vitamin B12 and Ni are known to interact and because of the similar metabolic roles of vitamin B12 and folate, an experiment was performed to determine the effect of dietary folate on Ni deprivation in rats. A 2 x 2 factorially arranged experiment used groups of nine weanling Sprague-Dawley rats. Dietary variables were Ni, as NiCl(2) 6H(2)0, 0 or 1 mu g/g; and folic acid, 0 or 2 mg/kg. The basal diet, based on skim milk, contained less than 20 ng Ni/g. After 54 d, an interaction between dietary Ni and folate affected several variables including erythrocyte folate, plasma amino acids, and femur trace elements. For example, folate deprivation decreased erythrocyte folate; folate supplementation to the Ni-supplemented rats caused a larger increase in erythrocyte folate concentration than did folate supplementation to the Ni-deprived rats. Also, dietary Ni affected several plasma amino acids important in one-carbon metabolism (e.g., Ni deprivation increased the plasma concentrations of glycine and serine). This study shows that dietary Ni, folate, and their interaction can affect variables associated with one-carbon metabolism. This study does not show a specific site of action of Ni but it indicates that Ni may be important in processes related to the vitamin B12-dependent pathway in methionine metabolism, possibly one-carbon metabolism.

Effect of nickel deficiency on biochemical variables in serum, liver, heart and kidneys of goats.

Nickel deficiency was induced in 2- to 4-year-old goats by feeding 0.1 mg Ni/kg dry matter with a semisynthetic diet. The control group consumed 5.0 mg Ni/kg d.m. Activity of several enzymes (SDH, LDH, HBDH, AST, ALT, ALD, CK, CHE) was determined in the serum, liver, heart and kidneys. Serum urea-N level was also measured and transmission electron microscopic (TEM) examinations were performed. Signs characteristic of nickel deficiency (retarded growth, increased mortality of dam and offspring, parakeratosis of the skin) appeared in the low-nickel group. The activity of SDH and ALD, as well as the level of urea-N was significantly lower in the serum of Ni-deficient animals than in the control. Ni-deficient animals also had significantly lower enzyme activities in the heart (SDH, HBDH, AST, ALT, ALD and CK), liver (SDH and CHE) and kidneys (HBDH and CK). Electron micrographs showed degeneration of cardiac and skeletal muscle in the Ni-deficient animals. Ni deficiency elicited changes primarily in the heart and these resulted in depressed activity of several enzymes.

[Nickel, an essential trace element. Metabolic, clinical and therapeutic considerations]. / Il nichel, un oligoelemento essenziale. Considerazioni metaboliche, cliniche e terapeutiche.

Having briefly analyzed the role of nickel in the living organism the author describes conditions induced by nickel poisoning and deficit. The most recent acquisitions concerning the importance of nickel in the stabilization of nucleic acids are also illustrated.

[Comparative characteristics of deficiency and excess of the same trace element (as exemplified by nickel)]. / Sravnitel'naia kharakteristika odnoimennykh gipo- i gipermikroélementozov (na primere nikelezov).

General rules of biological effects of essential trace elements in human and animal body are discussed as illustrated by nickel model. Their action depends on the dose and duration of exposition. 5 levels of their action depending on the elements concentration in the body are distinguished. Pathology of low and high content of the same element in spite of the contrast of these conditions has certain similarity in the coincidence of the target organs and some pathological manifestations.

Effect of dietary nickel deprivation on vision, olfaction, and taste in rats.

Early studies on dietary nickel deprivation found decreased reproduction rate in pigs and decreased insemination and conception rates in goats. Studies from our laboratory demonstrated that nickel deprivation impaired male reproductive function of rats. A physiological amount of nickel modulates the function of cyclic nucleotide-gated cation channels (CNG channels) in vitro. Thus, because CNG channels have important roles in spermatozoa function, it was speculated that the impairment of reproduction by nickel deprivation was through an effect on CNG channels. Because CNG channels are found in retinal photoreceptor, olfactory receptor, and taste receptor cells, we hypothesized that nickel deprivation would also alter light/dark preference, odor preference to female rat urine, and taste preference/aversion in rats. In the light/dark Y-maze, nickel deprivation significantly decreased time spent in the dark arm by rats. The number of sniffs to estrous female urine was significantly increased only in nickel-supplemented rats. The number of licks at the saccharin bottle was significantly decreased by dietary nickel deprivation. These findings suggest that nickel has a biological role in the special senses: vision, olfaction and taste.

Nickel deficiency disrupts metabolism of ureides, amino acids, and organic acids of young pecan foliage.

The existence of nickel (Ni) deficiency is becoming increasingly apparent in crops, especially for ureide-transporting woody perennials, but its physiological role is poorly understood. We evaluated the concentrations of ureides, amino acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni-S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch). Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but total ureides, urea concentration, and urease activity were reduced. Disruption of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine, valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids, and lower concentrations of histidine and glutamic acid. Ni deficiency also disrupted the citric acid cycle, the second stage of respiration, where Ni-D foliage contained very low levels of citrate compared to Ni-S foliage. Disruption of carbon metabolism was also via accumulation of lactic and oxalic acids. The results indicate that mouse-ear, a key morphological symptom, is likely linked to the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and margins of leaflets. Our results support the role of Ni as an essential plant nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan is evidence of the existence of unidentified physiological roles for Ni in pecan.

Studies on the role of nickel in the ruminant.

Lambs were fed 6 to 7% of metabolic body weight per day of a basal purified diet low in nickel (65 ppb) or the basal diet plus 5 ppm nickel for a 97 day period in an attempt to demonstrate an essential role for nickel in the ovine. Weight gains for the entire period and digestibility of dry matter and of protein at 28 and 56 days were not different between the two groups. At 28 days, but not at 56 days, urinary nitrogen was less and percentage retention of absorbed nitrogen was greater in the supplemented lambs. Total serum proteins were higher at 56 days and serum alanine transaminase was higher throughout the experiment in the nickel supplemented lambs, but only significantly so at 56 days. When lambs were given an oral dose of 65Ni, the low nickel lambs tended to excrete more in the feces and retained less in the kidney, lung, and liver at 72 hours post dosing. The major excretory route of nickel was via the feces. The kidney retained the highest concentration of 65Ni of the organs examined.

[Deficient nickel supply and the content of calcium, magnesium and phosphorus inthe bone of growing rats]. / Mangelnde Ni-versorgung und Ca-, Mg- und P-Gehalte in Knochen wachsender Ratten.

Based upon studies on Ni deficiency with marked changes in intermediary metabolism, the recent investigation examined the extent to which deficient Ni supply affects the content of calcium, magnesium and phosphorus in rat femurs. In Ni deficiency the content of calcium and phosphorus was reduced, in the case of calcium even more so than accounted for by the decrease in bone weight. The result was Ca : P ratio of 1.8 : 1 in Ni deficiency compared with 2.0 : 1 in control animals. In the case of magnesium, however, the Mg concentration was increased by 45% in the bone fresh matter of the deficient animals. The reduced Ca retention in the bone is accordingly contrasted by an enhanced deposition of magnesium.

Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations of the other trace elements.

Circumstantial evidence suggests that aluminum, arsenic, bromine, cadmium, germanium, lead, lithium, nickel, rubidium, silicon, tin and vanadium are essential. The evidence is most compelling for arsenic, nickel, silicon and vanadium. The estimated daily dietary intakes for these elements are arsenic, 12-50 micrograms; nickel, 100 micrograms; silicon, 20-50 mg and vanadium, 10-20 micrograms. By extrapolation from animal studies, the daily dietary intakes of these elements needed to prevent deficiency or to provide beneficial action in humans are arsenic, 12-25 micrograms; nickel, 100 micrograms; silicon, 2-5 mg (based on 10% bioavailability in natural diets) and vanadium, 10 micrograms. Thus, the postulated need by humans for these elements can be met by typical diets. Because there may be situations, however, where dietary intake does not meet the postulated requirements, research is needed to derive status indicators in humans and to further study the relationships of low intake or impaired bioavailability of these ultratrace elements to various diseases.

Malate dehydrogenase and glucose-6-phosphate dehydrogenase activity in livers of Ni-deficient rats.

In experiments using rats it was shown that inadequate dietary supply of Ni reduces growth and lowers the erythrocyte count, hematocrit and hemoglobin level in blood, that the Ni supply affects the trace element content of iron, copper and zinc in various body organs, and that the absorption of iron is greatly impaired by Ni deficiency. For further biochemical criteria on the essentiality of nickel, the activities of two dehydrogenases, malate dehydrogenase and glucose-6-phosphate dehydrogenase, were measured in liver homogenates from two generations of rats at 30 and 50 days of age. In the 30-day-old rats of both the F1 and F2 generation, the activity of the malate dehydrogenase fell to about two-thirds the level of control animals. In the liver of the 50-day-old rats the activity of this enzyme was about the same in deficient animals as in the controls. The activity of glucose-6-phosphate dehydrogenase of Ni-deficient rats was reduced by 85% in the F1 generation and by 56% in the F2 generation at 30 days of age as compared with control levels. In 50-day-old rats the activity had fallen to half the level of control animals at 30 days of age. At the age of 50 days, there was no significant difference between the deficient and the control groups of either generation.

Nickel deficiency in rats.

Nickel deficiency was produced in rats fed diet (containing 2-15 ng of mickel/g) based on dried skim mile, acid-washed ground corn, EDTA-extracted soy protein, and corn oil. Controls were fed a supplemental 3 mug of nickel/g of diet as NiCl2-6H2O. The rats were raised in plastic cages located inside laminar flow racks. Nickel deprivation resulted in several consistent pathological findings. These included: (1) increased perinatal mortality, (2) unthriftiness in young rats characterized by a rough coat and/or uneven hair development, (3) altered gross appearance (color) of the liver, (4) increased rate of alpha-glycerophosphate oxidation by liver homogenates, (5) decreased liver cholesterol, and (6) ultrastructural changes in the liver with the most obvious difference in the amount and organization of the rough endoplasmic reticulum. Nickel deficiency in rats tended to decrease growth, hematocrits, and liver total lipids and phospholipids.