maternal diet in rats and response of offspring to post-weaning infection

4
JUNE 19711 NUTRITION REVIEWS 147 seen in only two out of seven of the normal calcium intake group which also received lead. Although the femur weight remained unaffected by the normal calcium diet, whether lead was added or not, the femur weight decreased on the low calcium diet. Femur lead storage was about one-third as great on the normalcalcium-plus-lead diet, as that seen with the lowcalcium-plus-lead diet. These balance studies suggest that the mechanism by which the low calcium diet may increase lead toxicity is increased gastrointestinal absorption of lead. In addition, a low calcium diet may alter the whole body distribution of lead, perhaps mediated through parathyroid hormonal changes: these studies did suggest a much greater disparity in soft tissue lead than in bone lead, in response to the low calcium intake. There was also some evidence that ingestion of lead might influence calcium metabolism; at least blood levels of serum calcium were somewhat lower and phosphorus levels somewhat higher in the animals receiving lead. The authors suggest that this may reflect some competition between lead and calcium in transport. Although they were not measured in this experiment, vitamin D and parathyroid hormone are also important determinants of calcium metabolism and bone formation [Nutrition Reviews 26; 65( 19SS)l. These authors have again emphasized the importance of dietary factors in determining the organism’s response to lead exposure. Whether variations in dietary calcium would make as much difference when exposure is to inhaled particulate lead rather than ingested lead is an interesting question. It was shown many years ago that deposition of lead in the femur, when lead acetate was included in lab’ diets, could be effectively Lqcreased by lower dietary calcium, but the same effect was not seen when the lead was administered daily by intraperitoneal injection [L. B. Lederer and F. C. Bing, J. Am. Med. Assn. 114, 2457 (1940). Nonetheless, Six and Goyer have shown again that dietary calcium will affect not only the retention and deposition of lead, but the consequent effects of lead upon the hematopietic and renal systeigs. MATERNAL DIET IN RATS AND RESPONSE OF OFFSPRING TO POST-WEANING INFECTION Rats from darns fed diets deficknt or marginal in lipolropic factors were more susceptible lo in feclion with Salmonella typhirnurium than w r e mts from darns fed diets adeqwle in lipolropic faclors. This grealcr susceplibilily persisted even though the former animals were transferred of waning lo o diet adequate in lipotropic factors. These results prouide furthrr eL;denre of phvsiological defects lhcf ran result from inadequate maternal nutrition during gestation and lactation. Recently, considerable attention has M. 1. T. Press, Cambridge (1968)l. While been given to the possible effects of diet learning ability is the human being’s in early life on subsequent learning and most significant asset, how this ability behavior [Nutrition Reviews 28, 176 can express itself will be affected by the (1970); 27, 191 and 251 (1969); stresses of the individual’s environment, Malnutrition, Learning and Behavior, N. including chronic illness. Less attention S. Scrimshaw ond J. E. Cordon, Editors. has been given to the possible effects of

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Page 1: MATERNAL DIET IN RATS AND RESPONSE OF OFFSPRING TO POST-WEANING INFECTION

JUNE 19711 NUTRITION REVIEWS 147

seen in only two out of seven of the normal calcium intake group which also received lead. Although the femur weight remained unaffected by the normal calcium diet, whether lead was added or not, the femur weight decreased on the low calcium diet. Femur lead storage was about one-third as great on the normalcalcium-plus-lead diet, as that seen with the lowcalcium-plus-lead diet.

These balance studies suggest that the mechanism by which the low calcium diet may increase lead toxicity is increased gastrointestinal absorption of lead. In addition, a low calcium diet may alter the whole body distribution of lead, perhaps mediated through parathyroid hormonal changes: these studies did suggest a much greater disparity in soft tissue lead than in bone lead, in response to the low calcium intake. There was also some evidence that ingestion of lead might influence calcium metabolism; at least blood levels of serum calcium were somewhat lower and phosphorus levels somewhat higher in the animals receiving lead. The authors suggest that this may reflect

some competition between lead and calcium in transport. Although they were not measured in this experiment, vitamin D and parathyroid hormone are also important determinants of calcium metabolism and bone formation [Nutrition Reviews 26; 65( 19SS)l.

These authors have again emphasized the importance of dietary factors in determining the organism’s response to lead exposure. Whether variations in dietary calcium would make as much difference when exposure is t o inhaled particulate lead rather than ingested lead is an interesting question. It was shown many years ago that deposition of lead in the femur, when lead acetate was included in lab’ diets, could be effectively Lqcreased by lower dietary calcium, but the same effect was not seen when the lead was administered daily by intraperitoneal injection [L. B. Lederer and F. C. Bing, J. Am. Med. Assn. 114, 2457 (1940). Nonetheless, Six and Goyer have shown again that dietary calcium will affect not only the retention and deposition of lead, but the consequent effects of lead upon the hematopietic and renal systeigs.

MATERNAL DIET IN RATS A N D RESPONSE OF OFFSPRING TO POST-WEANING INFECTION

Rats from darns fed diets d e f i c k n t or marginal in lipolropic factors were more susceptible lo in feclion with Salmonella typhirnurium than w r e mts from darns fed diets a d e q w l e in lipolropic faclors. This grealcr susceplibilily persisted even though the former animals were transferred o f w a n i n g lo o diet adequate in lipotropic factors. These results prouide furthrr eL;denre of phvsiological defects lhcf ran result from inadequate maternal nutrition during gestation and lactation.

Recently, considerable attention has M. 1. T. Press, Cambridge (1968)l. While been given to the possible effects of diet learning ability is the human being’s in early life on subsequent learning and most significant asset, how this ability behavior [Nutrition Reviews 28, 176 can express itself will be affected by the (1970); 27, 191 and 251 (1969); stresses of the individual’s environment, Malnutrition, Learning and Behavior, N. including chronic illness. Less attention S. Scrimshaw ond J. E. Cordon, Editors. has been given to the possible effects of

Page 2: MATERNAL DIET IN RATS AND RESPONSE OF OFFSPRING TO POST-WEANING INFECTION

148 NUTRITION REVIEWS [ Vol. 29. No. 6

early nutrition, especially maternal nutrition, on the response of the offspring to postnatal infection. This possibility has been investigated by P. M. Newberne, R. B. Wilson, and G. Williams [Brit. J. Exp. Path. 51, 229 (1970)]. As Newberne and co-workers pointed out, “In human populations, the underprivileged groups which suffer from the basic condition of malnutrition are also subjected to a physical, social, and biological environment conducive to increased frequency and chronicity of infection. Repeated gastrointestinal and respiratory @fections result in a cycle of decreased food intake, increased metabolic demands, and probably a decrease in absorption of nutrients. These factors all contribute to a further deterioration of the nutritional state.”

These workers investigated the effect of the maternal and post-weaning diet on the response of the offspring to a standard infection with Salmonelk typhimurium. This work arose from a previous study of the effect of maternal diets marginal in lipohpic factors (choline, methionine, and vitamin B, ) on the developing rat fetus [Newberne and A. Ahlstrom, Fed. Proc. 28, 556 (1969)l. The dams were fed diets which differed in the levels of choline, methionine, and vitamin B,, during gestation and lactation. Upon weaning, the young rats were continued on the same diet previously fed their dams, or were transferred to a diet adequate in lipotropic factors.

Diet I (deficient) and Diet I1 (marginal) contained 18.2 per cent alpha-protein (low in sulfur amino acids), 23.6 per cent cornstarch, 42.6 per cent sucrose, 9.1 per cent cottonseed oil, 4.6 per cent Hegsted salt mixture, and 1.8 per cent vitamin supplement (complete except for choline and vitamin B, ). Diet I also contained 0.1 per cent DL-methionine, and 0.1 per cent choline, and ldcked vitamin B, I .

Diet II had the same levels of methionine and choline as Diet I, but also contained 415 pg. vitamin B,

Diet 111 (moderate) and Diet IV (complete) contained 18.0 per cent alpha-protein, 23.6 per cent cornstarch, 42.5 per cent sucrose, 9.0 per cent cottonseed -oil, 4.5 per cent mineral mixture, and 1.8 per cent vitamin supplement (lacking choline and vitamin B12). Diet 111 contained 0.3 per cent DL-methiOnine and 0.3 per cent choline, but lacked vitamin B, 2 . Diet IV had the same levels of methionine and choline as Diet 111, but contained also 4.5 pg. vitamin Bt per 100 g. diet.

Survival of the young from the dams fed diet I (deficient) was low. Survival of the young from the dams fed the other three diets was approximately the same. At weaning the young from the dams fed diets 1, 11, and 111 were divided into two groups. One group continued to receive the diet fed the dams during gestation and lactation. The other groups were shifted to diet IV (complete). The average weaning weight was about 25 g. in the rats from the dams fpd the deficient diet and about 34 to 37 g. in the offspring of the dams fed thg other three diets.

At 100 days after weaning, the young rats were infected with S. typhirnurium, injected intrapentoneally. At the time of infection, body weights of the rats from the dams fed the deficient or marginal diets (I and 11) were significantly lower than those of the rats from darns fed the moderate or complete diets (Il l and IV) and then given the complete diet after weaning. Feeding the complete diet to the young rats from diet I darns did not increase body weight (240 g.) significantly in comparison with the rats (233 6.) maintained continuously on the deficient diet (1). The rats from dams fed the marginal diet (11) and transferred to the complete diet grew significantly more (285 g.) than those fed the

per 100 g.

- I

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J U N E 19711 NUTRITION REVIEWS 149

marginal diet for the entire period (248 g.). Likewise, the rats from the dams fed the moderate diet (111) and then transferred to the complete diet grew significantly more (308 g.) than the rats maintained on the moderate diet throughout (260 g.).

Upon infection, mortality within seven days was 100 per cent in the group fed the deficient diet ( I ) continuously and was 80 per cent in the group from darns fed diet I and then shifted to diet 1V. At 14 days, mortality in this group was also 100 per cent. In the groups from the dams fed the marginal diet (II), mortality at seven days was 50 per cent in those continued on diet 11 and 40 per cent in those transferred to the complete diet (IV) a t weaning. By 30 days, however, mortality in both groups was 90 per cent.

In the rats maintained continuously on the diet with moderate amounts of lipotropic factors (111). mortality at seven days was 47 per cent and 71 per cent at 30 days. However, in the group from dams fed diet 111 and then transferred to the complete diet, mortality at seven days was 20 per cent and was 35 per cent at 30 days. This compared favorably with the group given the complete diet for the entire period, in which rncrtality was 10 per cent at seven days and 25 per cent a t 30 days.

Determinat ion of hemoglobin. hematocrit, and total white blood cell count a t pre-infection and at 72 hours post-infection showed that the diet fed in the gestation and lactation period also affected these blood values, both before and after infection. The rats from dams fed the deficient diet ( I ) showed a lower hemoglobin concentration both pre- and post-infection. Hematocrit and total white cells were also significantly lower at 72 hours post-infection than in the other groups. In the tat. exposed continuously to the marginal diet (11). the white cell count was also lower

post-infection, but in the group from the dams fed diet I1 and transferred a t weaning to diet IV, the white cell and hematocrit values were significantly higher. They were, however, still lower than those in the rats maintained continuously on the complete diet.

Rats maintained continuouslj, on the moderate diet (111) had a pre-infection hematocrit value somewhat lower than that of the group maintained continuously on the complete diet. This lower hematocrit persisted in the post-infection period, when the white cell count was also lower in these rats. The rats from dams fed the moderate diet but who were transferred at weaning to the complete diet showed the same blood values at pre-infection as did the rats maintained continuously on the complete diet. However, the mts in the former group showed somewhat lower hematocrit and white cell counts in the post-infection period.

In t h e second experiment, aU the young rats were maintained after weaning on the Same diets fed their darns during gestation and lactation. To determine whether the greater food intake was responsible for the better response to infection in the rats fed the diets higher in lipotropic factors, one group on each of the diets was pair fed to the food intake of t he rats fed the deficient diet (1). The pair fed groups gained Iw weight than the groups fed the same diet ad libitum, but the weight gains were still greater than those of the rats fed the deficient diet ad libitum. However, the per cent of mortality at 30 days after infection was the same in the pair fed and the ad libitum fed groups.

S e r u m p ro te in analyses a t pre-infection and 72 hours postinfection were also done in the groups from the pair feeding experiment. Food restriction did not significantly affect total serum protein, albumin, or the amounts of alpha-, beta-, or gamma-

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150 NUTRITION REVIEWS 1Vol. 29, No. 6

globulins. Total protein, albumin, and beta- and gamma-globulins were signi- ficantly lower in the rats fed the deficient diet ( I ) than in the groups fed the moderate or adequate diets (111 and IV). Gamma-globulin and total protein were also lower in the groups fed the marginal diet (11).

At 72 hours after infection, serum albumin values decreased in' all groups, but the decrease was greatest in groups I and 11. These groups also showed no increase in gamma-globulin, whereas this fraction doubled in the groups fed diets I11 and IV.

The lower Serum protein values in the rats from the d a m s fed the deficient or marginal diets, together with the failure of gamma-glob- and white cell counts to increase normally in these groups

after infection, art? evidence that the immunologic system is seriously affected by a deficiency of lipotropic factors. Furthermore, these defects could not be remedied by an improved diet in the post-weaning period since, in the first experiment, feeding the complete diet to the young from dams fed deficient or marginal diets did not improve their abiiity to survive infection, in comparison with the rats maintained throughout the experiment on the inadequate or marginal diets. Thus. one may conclude that exposure to these inadequate diets during prenatal and early postnatal life made the animals more susceptible to later infection, perhaps by reducing permanently their ability to form antibodies.

EFFECT OF CALCITONIN ON BONE RESORPTION INDUCED BY EXCESS VITAMINS A AND D

Calcitonin inhibits the bone resorption and hypercalcemia resulting from massive doses of vitamin A or of vitamin D in young mk.

T h e in i t ia l report of a calcium-regulating hormone in addition to parathyroid hormone [D. H. Copp et al., Endocrinology 70,638 ( 1 9 S Z ) l was soon followed by evidence that the major effect of this newly discovered hormone, calcitonin, is directly on bone. Both in vitro [J. Friedman and L. G. Raisz, Science 150,1465 (1965)l and in vivo [ G . V. Foster et al., Am. J. Med. 43, ' 691 (1967)l techniques yielded the finding that calcitonin inhibits bone resorption u n d e r p h y s i ological conditions. This apparently accounts for its hypocalcemic effect.

Two recent papers have reported that abnormal rates of bone resorption, induced by pharmacologic doses of vitamin A or of vitamin D. can be prevented or decreased by calcitonin.

In studying the effect of calcitonin on vitamin A-induced changes in bone in the rat, H. Matrajt-Denys e t al. [Endocrinology 88. 129 (1971)l used three groups of 12 male Wistar rats initially weighing 67 g. For four weeks all animals were fed a stuck diet and were given daily subcutaneous injections of a gelatin-acetate buffer which was the carrier for 100 MRC mU (Medical Research Council milliunits) of porcine calcitonin given daily to the third group of animals. Both the second and third groups received vitamin A acetate, injected subcutaneously in a dose of 2.500 1.U. three times weekly. Group one served as a control, receiving neither hbrmone nor vitamin. Body weights were recorded weekly but no measure of food intake was made. A t the end of the