Search

Significant advances have been made in the past year in our understanding of the structure, function, and mode of regulation and assembly of nickel-containing enzymes. The highlight of 1997 was the elucidation of the methyl-CoM reductase structure.

The present investigation was designed to examine the effect of nickel deficiency on lipid metabolism in liver and serum lipoproteins of rats. Therefore, a study over two generations was conducted feeding a nickel-deficient diet containing 13 microg/kg nickel or a nickel-adequate diet supplemented with 1 mg/kg nickel. Male 7-wk-old pups from the second offspring were studied. Pups fed a diet poor in nickel tended to have lower weight gains (P < 0.15), nickel concentrations in liver (P < or = 0.1) and iron levels in serum (P < 0.1) than nickel-adequate rats. They were classified as nickel-deficient on the basis of significantly lower erythrocyte counts, hemoglobin concentrations, hematocrits and nickel concentrations in kidney compared with nickel-adequate rats. Nickel deficiency caused a significant triacylglycerol accumulation in liver, with greater concentrations of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids than nickel-adequate rats. Nickel deficiency had slight but significant effects on the fatty acid composition of liver total lipids and phosphatidylcholine and phosphatidylethanolamine. Moreover, nickel-deficient rats had significantly lower activities of the lipogenic enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and fatty acid synthase than nickel-adequate rats. Nickel-depleted pups had significantly higher concentrations of triacylglycerols and phospholipids in serum VLDL, and cholesterol in serum LDL than nickel-adequate pups. Most of these alterations in lipid metabolism are similar to those obtained in several iron-deficiency studies. Because nickel deficiency also slightly compromised iron status, it is possible that at least some of the observed alterations are due to the moderate iron deficiency.

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.

A study involving three experiments was done to ascertain whether the beneficial effect of nickel on hematopoiesis in moderately iron-deficient rats was due to physiologic and/or pharmacologic mechanisms. Female Sprague-Dawley rats were fed nickel supplements ranging from 0 to 100 micrograms/g in iron-low (15 micrograms Fe3+/g), iron-adequate (65 micrograms Fe3+/g), or iron-luxuriant (100 micrograms Fe3+/g) diets. The basal diet contained from 2 ng (experiment 3) to 36 ng (experiment 1) of nickel/g. At 10 weeks, both nickel deficiency and toxicity (100 micrograms/g diet) tended to depress hematopoiesis and markedly altered femur and liver trace element content in marginally iron-deficient rats. The alterations included elevated copper, iron and nickel, and depressed calcium and manganese in femurs. The pharmacologic action of nickel was indicated by the finding that high dietary nickel (5, 10, 20 or 50 micrograms/g) apparently stimulated hematopoiesis in marginally iron-deprived rats to a greater extent than dietary levels of nickel (0.1, 0.5 or 1.0 microgram/g) considered adequate for nutritional needs. High dietary nickel also elevated the iron content in liver of marginally iron-adequate rats. The findings indicate that nickel influences iron metabolism at physiologic, pharmacologic and toxic levels of intake. They also indicate that many previously reported signs of nickel deprivation, including effects on hematopoiesis, may have been misinterpreted and might be manifestations of pharmacologic actions of nickel.