[Interactions of manganese with copper in various organs of the rat under adequate and deficient Mn supply].
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Biomedical subjects
Publications and source records attributed to M Kirchgessner.
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In previous studies on the essentiality of nickel, a reduced iron absorption causing anemia was observed. Since Ni deficiency also affects Zn metabolism, the different phosphatase activities were determined. Ni deficiency, however, resulted in an increased activity of the alkaline phosphatase in liver. On the other hand, the activity of the alkaline phosphatase was deduced by 59% during Fe deficiency. Similarly, the alkaline and acid phosphatases in serum were reduced during Fe deficiency. Consequently, determination of the activity of the alkaline phosphatase in serum, besides that of various liver enzymes, is suited well to differentiate between Fe and Ni deficiency.
Thirty-five male weanling Sprague-Dawley rats with an average live weight of 32 g were divided into three groups. The Zn-deficient group of 14 animals was given 1.3 mg Zn/kg of diet for 23 days, while the pair-fed control group with 14 animals and the ad libitum fed control group with 7 animals were both fed 100 mg Zn/kg of diet. Serum was assayed for triglycerides, total lipids, cholesterol, cholintesterase, free fatty acids and beta-lipoproteins, and duodenal juice for trypsin. While the serum concentrations of beta-lipoprotein, total lipids and total cholesterol were not different in response to Zn deficiency, the activity of the cholinesterase activity was reduced, the triglyceride concentrations and trypsin activity increased. Similarly, the serum free fatty acids were elevated compared to the ad libitum fed controls. This disturbances in Zn-deficient rats are discussed in connection with the lipid metabolism.
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In a comparative slaughter experiment the copper, manganese and zinc contents in different organ and tissue samples of veal calves at different weights were determined by whole body analyses. For all three trace elements, a decrease of their concentration with increasing age could be observed in the individual parts (blood, adipose tissue, innards, meat, bones) and in the whole body. During the fattening period of 12 weeks the concentrations in the dry matter of the whole body decreased from 12 ppm to 5 ppm copper (P less than 0.001), from 3.5 ppm to 1.6 ppm manganese (P less than 0.05) and from 127 ppm to 69 ppm zinc (P less than 0.05). In the present experiment the animals retained an average of 20 to 22% of the copper intake and about 20% of the manganese intake over the entire feeding period. Zinc was utilized at the extent of 40 to 43%. For the edible parts of the whole body the following coefficients of utilization were obtained: Cu = 10%, Mn = 7%, Zn = 30%.
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.
1. Kinetic experimetns were done with pepsin (EC 3.4.4.1) using haemoglobin as a substrate in the presence of different metal cations. 2. The activation of peptic hydrolysis with higher concentration of cupric ions added to the reaction mixture was determined from turnover-rate curves in experiments with constant substrate concentration. With a Cu2+ concentration greater than 1.67 X 10(-4) M activation was obtained. 3. Nickel ions at a concentration of 8-33 X 10(-4) M and at higher concentrations also increased pepsin activity. Additions of ferrous ions and zinc ions had no effect. 4. Experiments were done using variable substrate concentrations in the presence of different Cu2+ concentrations. The concentrations of haemoglobin ([S]) at half maximum velocity were determined. The double-reciprocal plots of [S] v. reaction velocity (v) (i.e. 1/[S] v. 1/v) had no common intersection point. Therefore the kinetics did not correspond to any of the known kinetics. The activation brought about by Cu2+ cannot easily be explained by the study of the kinetics. Certain simple explanations of the phenomenon can be eliminated.
2 groups of male calves (Braunvieh) each comprising 5 animals with liveweights, at the day of slaughtering, of 58 kg, 99 kg and 155 kg were used in a trial that was carried out to obtain data on the utilization of dry matter, crude protein, crude fat and ash in the bipartite feeding of calves. The nutrient content of the animals was determined by total body analysis. The following values for nutrient retention were obtained in comparative slaughtering trials by using differentiation techniques. No significant differences between the two fattening periods were observed concerning the utilization of total dry matter in the milk substitutes. About 24% of the dietary dry matter were retained. The mean value for the utilization of dietary fat during the whole period of fattening was found to be about 55% provided, the fat was not used as energy source to meet maintenance requirements. 49% of the milk proteins were utilized for both retention and maintenance in the first period of fattening and 55% during the second period. Differences between the two periods showed no consistent trend. In view of the fact that for all animals used in the trial digestibility was taken to be 95% the utilization coefficients for the digested crude protein were higher by about 3% compared with the figures for crude protein. After subtraction of maintenance needs it was found that, on an average, 63% of the residual amount of digested protein available over the whole fattening period were retained in the body. 55% to 57% of the retained protein were deposited in those parts of the body of the animals that are used for human nutrition. It is for this reason that in the first half of the fattening period only 29.8% of the ingested dietary proteins were retained in the edible cuts of the animal body, as compared with 30.4% during the second half of the fattening period.
Model experiments were carried out with rats showing that the average Ni concentrations in the milk of the experimental animals receiving a Ni deficient diet (40 ppb of dietary Ni), relative to those of the controls (20 ppm), declined from 1088 ng/g to 726 ng/g (33%). This produced a Ni deficiency in the youngs of the rats resulting in retarded growth, reduced Fe absorption and a decline in enzymatic activity. An increase in the Ni content of the milk from both the experimental animals and the controls was observed during lactation. In the Ni deficient group this upward trend was longer noticeable from about the middle of the lactation period onwards. Animals in the Ni deficient group excreted about three times as much Ni through the milk as was ingested with the food. Because of the wide range of deviations of the Ni content in the different animals the Ni content of the milk cannot be used, under practical conditions, as an index of a state of Ni deficiency.
5 lactating cows were used in a trial to investigate the process of Zn absorption and Zn retention under conditions of Zn deficiency and variations in Zn supplementation. The apparent Zn absorption was found to be markedly increased if the animals were fed a Zn deficient semisynthetic diet containing 6 mg Zn per kg of dry matter during the depletion period. Apparent Zn absorption continued to rise with continuing Zn depletion. Over a period of 6 weeks of Zn depletion the mean rate of Zn absorption was 58% with increases from 51% to 64% between the 1st and 6th week of experiment. After 19 weeks of Zn depletion 75% of the supplemented zinc were absorbed. With a Zn supply of 22 ppm and 54 ppm the rate of apparent Zn absorption decreased to 51% and 44% while still higher Zn supplements, up to 436 ppm, produced only a slight further decline down to 40%. The absolute Zn balances were shown to be directly associated with the level of Zn supply, all the more so because a linear relationship was found to exist between the levels of alimentary zinc supplementation and absolute Zn retention. Under conditions of Zn deficiency the cows exhibited a negative Zn balance, where animals with the highest milk yields showed the most negative Zn balances and remained for the longest period in the negative phase. With increasing periods of Zn depletion a homeostatic mechanism of Zn regulation in the organism of the animals became more and more pronounced so that at advanced stages of Zn depletion Zn retention of some extent occurred.
Trials with graded Cu supplementation were carried out to establish the minimum and optimum Cu demands of pregnant, lactating and non-pregnants rats. The rats were investigated for the rate of live weight gains of the dams and young rats, for the number of stillbirths and, in particular, for the Cu status in the liver, body and blood serum of the animals and for coeruloplasmin activity. All Cu values obtained from the organs investigated had reached a saturation level at 8 mug Cu/g diet with the exception of the values for body Cu found in the dams that were killed on the day of delivery. The same results were obtained, for the above criteria, with lactating rats. So, it may be concluded that pregnant and lactating rats receive an optimum supply of Cu when they are fed a starch + casein diet containing 8 ppm Cu. For non-pregnant female rats, the limits that might be regarded as adequate were even below the 8 ppm level of dietary Cu. The saturation level for Cu was also found to be dependent, in regard of the criteria investigated, on the physiological state of the animals. It was found that, on the day of parturition, the level of Cu concentration and coeruloplasmin activity in the serum of the dams and the Cu content in the liver of the new-born rats were the best indicators for the state of Cu supply to the dams. However, after a sucking period of 17 days, the level of total Cu content in the dams was found to respond very sensitively to changes in the Cu supply.