Pair-fed Control Group Research Articles

Decreased Plasma Lecithin:Cholesterol Acyltransferase Activity in Copper-Deficient Rats

The effect of dietary copper deficiency on rat plasma lecithin: cholesterol acyltransferase (LCAT) activity was examined. Three groups of rats were used: ad libitum-fed copper-deficient group (0.6 µg Cu/g diet); pair-fed control group (5.9 µg Cu/g diet); and an ad libitum-fed control group (5.9 µg Cu/g diet). Copper deficiency produced a significant hypercholesterolemia (57% increase, P < 0.001) in 63 days with a significant increase in plasma free cholesterol (44%, P < 0.001). Despite the significant increase in plasma free cholesterol, fractional and molar LCAT activity were markedly decreased (74.2%, P < 0.001 and 63.7%, P < 0.005, respectively) in copper-deficient rats. The results of this study suggest that dietary copper deficiency affects LCAT activity.copper deficiency LCAT activity cholesterol esterification

ERYTHROCYTOSIS IN THIAMINE DEFICIENT RATS

AbstractA thiamine (T) deficient state in rats was produced by feeding the rats a T deficient diet (TDD). At the stage of 13 days (TDD1 3 group), the number of red blood cells (RBC) and white blood cells (WBC), hematocrit (Ht) and hemoglobin (Hb) values decreased. On the other hand, after 30 days on the TDD (TDD30 group), the number of RBC was 819×104/mm3 as against 631×104/mm3 in the normal control group (NC group). Ht and Hb values also increased in the TDD30 group. These changes observed in the TDD30 group were significantly different from findings in the equal weight control group (EWC group) or in the pair fed control group (PFC group). The number of reticulocytes increased, the levels of 2,3-diphos-phoglycerate (2,3-DPG) of RBC decreased and plasma erythropoietin levels increased in the TDD30 group. T levels of blood in the TDD13 group were 62 (39–79) ng/ml as against 275 (196–412) ng/ml in the NC group. T levels of blood in the TDD30 group were 102(17–b365) ng/ml, and widely varied. Decrease in 2,3-DPG produces an increase in O2 affinity to Hb, and hypoxia is induced in the peripheral tissues. Furthermore these conditions stimulate erythropoietin production and finally the number of RBC increases. T deficiency produces anemia at an early stage and absolute erythrocytosis occurs at the late stage of T deficiency. The increased osmotic resistance of RBC in hypotonic solution was also observed in the TDD30 group. This increase in osmotic resistance correlated with the decrease in cholesterol and phospholipid levels in the membrane of RBC.

Erythrocytosis in thiamine deficient rats.

A thiamine (T) deficient state in rats was produced by feeding the rats a T deficient diet (TDD). At the stage of 13 days (TDD13 group), the number of red blood cells (RBC) and white blood cells (WBC), hematocrit (Ht) and hemoglobin (Hb) values decreased. On the other hand, after 30 days on the TDD (TDD30 group), the number of RBC was 819 x 10(4)/mm3 as against 631 x 10(4)/mm3 in the normal control group (NC group). Ht and Hb values also increased in the TDD30 group. These changes observed in the TDD30 group were significantly different from findings in the equal weight control group (EWC group) or in the pair fed control group (PFC group). The number of reticulocytes increased, the levels of 2,3-diphosphoglycerate (2,3-DPG) of RBC decreased and plasma erythropoietin levels increased in the TDD30 group. T levels of blood in the TDD13 group were 62 (39-79) ng/ml as against 275 (196-412) ng/ml in the NC group. T levels of blood in the TDD30 group were 102 (17-365) ng/ml, and widely varied. Decrease in 2,3-DPG produces an increase in O2 affinity to Hb, and hypoxia is induced in the peripheral tissues. Furthermore these conditions stimulate erythropoietin production and finally the number of RBC increases. T deficiency produces anemia at an early stage and absolute erythrocytosis occurs at the late stage of T deficiency. The increased osmotic resistance of RBC in hypotonic solution was also observed in the TDD30 group. This increase in osmotic resistance correlated with the decrease in cholesterol and phospholipid levels in the membrane of RBC.

The Effects of Whole-body Irradiation on the Serum Levels and Kinetics of Thyroid Hormones in Rats

The effects of a single whole-body dose of X-rays on the serum levels and kinetics of thyroid hormones in rats were studied. The influence of radiation-induced anorexia was monitored by using pair fed control groups. A dose of 800 rad caused a reduction in T4 levels and 750 rad had a similar effect on T3; in each case the control group showed a smaller reduction. The kinetic results indicated that, in the control groups, the early reduction in hormone concentrations was caused, by a change in the distribution of the hormone; however, the continuing reduction in hormone levels in the irradiated rats appeared to results from decreased production. The results suggest that the thyroid system may play an active part in the early metabolic changes which follow whole-body irradiation.

Effects of dietary lead and zinc on pregnancy

In order to further understand the effects of ingested Pb on pregnancy and the possible interaction of the trace element Zn with Pb, groups of dated, pregnant rats were fed 10, 50, 100, 200, or 500 mg/L of Pb in water throughout pregnancy. R control group with no Pb, but diet ad lib, and a pair-fed control group with no Pb were also studied. Maternal average daily food consumption was significantly reduced at 50 mg/L of Pb and up. Total and net maternal weights were significantly reduced at 50 mg/L of Pb and up. Pair feeding at the 200 mg/L level improved maternal weight gain but not to control levels. Zn, 200 mg/L, supplement at the 200 mg/L of Pb level caused no improvement nor did ad lib diet with Pb removed-after 16 days. Fetal weight decreased progressively as Pb levels were increased. Pair feeding at the 200 mg/L Pb of level and Zn, 200 mg/L, supplement with 200 mg/L of Pb significantly increased fetal weight but not to control levels. Placental weight was unchanged throughout. The results indicate that Pb-induced fetal growth retardation is due to reduced maternal food and energy intake, as well as to direct effect on the fetus. Excess dietary Zn improves fetal growth, probably by increasing maternal food consumption.

Characteristics of Thyroid Function in Experimental Protein Malnutrition

Two experiments were conducted to study the effects of protein malnutrition on thyroid function. Resting oxygen consumption and serum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) were measured and correlated with thyroid histology, gain in weight, feed efficiency and carcass energy content in male rats fed isoenergetic diets ad libitum containing 22% (control) or 8% (protein malnourished, PM) casein for 28 or 32 days postweaning. A third group was pair-fed to the PM rats with the control diet. In experiment 2 additional groups were pair-fed to the PM rats with 8% casein diets in which the casein was substituted with different mixtures of carbohydrate and fat. Resting oxygen consumption/body weight (0.75) decreased as body weights increased in all groups, but was consistently greatest in PM rats. In PM rats, plasma T3 was 130% of controls after 11 days of the dietary regimen and averaged 215% of controls from days 18 through 32. In experiment 2 both T3 and T4 concentrations were approximately twice controls in all PM groups. TSH concentrations were within the normal range in all groups throughout. Feed efficiency averaged 36 to 40% of controls and mean weight gain was 30 g after 28 days in the PM groups, compared to 114 and 91 g, respectively, in the pair-fed control rats. Carcass energy content of PM rats after 28 days was significantly lower than in control or pair-fed control rats. Thyroid morphology was compatible with increased secretory activity in all the protein-malnourished groups, compared with normal activity in the control and pair-fed control groups. Thermogenesis, as measured by oxygen consumption, was markedly increased in the PM rats compared to controls. These observations are consistent with a diet-induced thermogenesis in the protein-malnourished rats. In contrast to simple under-nutrition where energy expenditure may be conserved by decreases in thyroid function and thermogenesis, increases in thyroid function and thermogenesis in protein malnutrition could provide an energy balancing mechanism whereby unneeded non-protein energy in the diet could be dissipated as heat, and survival enhanced.

Effect of Vitamin B-6 Deficiency on Preference for Several Taste Solutions in the Rat

The effect of dietary-induced vitamin B-6 (B-6) deficiency on the intake of the taste solutions, sodium chloride (NaCl), sodium saccharin (NaSacc), quinine sulfate (QS), and hydrochloric acid (HCl) was studied using a 48 hour, two-bottle choice technique. The B-6 deficient group demonstrated increased preference to 1.5 X 10(-1) and 3.0 X 10(-1) M NaCl compared to control ad libitum fed and control pair-fed groups. Total fluid intake on NaCl test days was also elevated in the B-6 deficient rats. There was no significant difference in the mean preference to NaSacc, QS, or HCl among the three groups. Adrenal hypertrophy was observed in the deficient rats. There was no change in the plasma level of Na and Zn but there was a reduction in urinary Na excretion. When the deficient rats were replenished by intraperitoneal injection of pyridoxine.HCl and feeding with the control diet containing adequate B-6, the increased preference for NaCl was extinguished, suggesting that the preference alteration was reversible. Urinary Na excretion also returned to normal.

Liver glycogen after portacaval shunt in rats

Theories to explain the metabolic effects of portacaval shunt (PCS) have frequently failed to take into account the sequelae of PCS-induced anorexia. In this study PCS rats, followed up to 42 days postoperatively, had a lower food intake than ad libitum-fed (ALC) controls and also lost 10% body wt compared to a 20% gain of ALC rats. Liver weight was significantly reduced in PCS rats compared to ALC rats, pair-fed sham-operated (S) and pair-fed normal control (PFC) rats. However, liver glycogen was equally reduced in all animals with reduced food intake (PCS, S, and PFC rats) compared to ALC rats. Plasma glucose was significantly lower in PCS rats and PCS rats had markedly elevated plasma glucagon and lower plasma insulin concentrations than ALC rats, with the result that they had a low insulin: glucagon molar ratio of 1.3:1 compared to 10.2:1 in the ALC rats. The pair-fed control groups had intermediate I:G ratios and plasma glucose concentrations, thus an inverse relationship between mean plasma glucose and mean I:G ratio for each group was found, suggesting that the blood glucose concentration was the primary event determining the I:G ratio for each group. These controlled experiments indicate that hepatic atrophy after PCS appears to be directly related to the shunting of portal blood away from the liver, while reduced liver glycogen is related to decreased food intake. Reduction in total body weight, relative hypoglycemia, and elevated I:G ratios appear to be due to a combination of factors.

Impaired myocardial performance and response to calcium in experimental alcoholic cardiomyopathy

The effect of chronic consumption of ethanol upon myocardial function has been in dispute. The mechanical performance of isolated left ventricular papillary muscles was studied in a group of eight male rats which had been on a diet in which ethanol provided 36% of total calories for 5 weeks. This group was compared to a pairfed control group of eight rats. Muscles were studied in oxygenated Krebs-Henseleit solution at 28°C, while stretched to Lmax and stimulated at 12/min to contract isometrically. Bath calcium concentrations were varied from 1.25 to 7.5 mm/l. Heart size and chamber weights did not differ between the groups. Peak developed tension, maximum rates of rise and fall of tension, and time to half relaxation were significantly lower in the ethanol group, whereas resting tension and time to peak tension did not differ in the two groups. All parameters except time to half relaxation exhibited a significant dependence on concentration of calcium in the bath. However, the degrees of augmentation of peak developed tension and maximum rates of rise and fall of tension with increase in calcium in the bath from 1.25 to 2.5 mm/l were significantly lower in the ethanol group. In addition to impairment of function with chronic alcohol administration, altered sensitivity to calcium was demonstrated. Thus, isolated muscle studies have defined a defect in defined a defect in myocardial performance not apparent from studies of hemodynamics in the intact animal.

Effects of ethanol on pregnant rats and their offspring.

Pregnant rats were intubated with either 1.0 or 2.0 g/kg of ethanol daily throughout gestation. Pair-fed vehicle-treated, and nontreated rats fed ad libitum, served as control groups for ethanol-treated animals. Ethanol treatment reduced food and water consumption and attenuated the gain in body weight of pregnant animals relative to nontreated animals fed ad libitum. Litter size, litter weight, and the mean weight per pup were reduced in both the ethanol-treated and pair-fed control groups. There was no evidence of gross malformations in any of the off-spring. Since the reduction in litter size and litter weights did not differ significantly between ethanol-treated and pair-fed controls, the effects of treatment with ethanol appeared to be related to a reduction in maternal intake of calories rather than to the direct effect of ethanol on the developing fetus. There were no significant differences between any of the groups of offspring on one-way shock avoidance learning, water maze escape learning, spontaneous alternation, or brightness discrimination learning in tests beginning at 75 days of age. Thus, at the doses of alcohol used in this study, there was no evidence of behavioral teratogenesis comparable to that reported for higher doses in animals or in man characterized by the fetal alcohol syndrome.

Effect of dietary indole-3-carbinol on the induction of the mixed-function oxidases of rat tissue

Indole-3-carbinol (IC), a compound present in cabbage and other cruciferous vegetables, was fed for 3 wk to young male Sprague-Dawley rats at dietary levels of 50, 500, 5000 and 7500 ppm. Because lower body weights were recorded in the animals fed the two highest levels of IC, pair-fed control groups of rats were used in a second experiment. Increased relative liver weights with enhanced activities of hepatic aminopyrine- N-demethylase, p-nitroanisole O-demethylase and aryl hydrocarbon hydroxylase (AHH) accompanied by higher cytochrome P-450 levels were observed only in the rats fed the two highest levels of IC either ad lib. or in the paired-feeding study. AHH activity increased also in the kidney, with enhanced glucuronide excretion, in the rats fed either of the two highest levels of IC. Intestinal AHH exhibited a significant induction only as a result of the 7500-ppm treatment. The dose-response relationships differed among the tissues. The induction of tissue mixed-function oxidases by only extremely high dietary levels of IC supports the conclusion that this indole is not the specific vegetable constituent that induces these enzymes in rats fed Cruciferae.

Testicular effects of cyclohexylamine hydrochloride in the rat

Testicular effects of cyclohexylamine hydrochloride (CHA) were investigated in Wistar and Sprague-Dawley rats. Groups of 25 rats were fed diets containing 6000, 2000 and 600 ppm CHA for 90 days and in addition ad lib., pair-fed and paired-weight control groups were used to assess the role of reduced food intake in the development of testicular lesions. Rats fed diets containing 6000 and 2000 ppm CHA showed significant decreases in food consumption, body weight and body weight gain. However, significant increases in the incidence of testicular lesions were found only in those animals fed 6000 ppm CHA. Absence of a similar incidence of lesions in either the paired-weight of pair-fed control groups indicated that inanition was not primarily responsible for the development of the lesions. The toxicological significance of these findings is discussed.

Glycolytic, Hexose Monophosphate Shunt and Bactericidal Activities of Leukocytes in Ascorbic Acid Deficient Guinea Pigs

It is well known that glycolytic and hexose monophosphate shunt activities of leukocytes increase during phagocytosis. The relevance of these metabolic changes to particle uptake and particle destruction is also well established. In the present study, these metabolic activities were studied to assess the phagocytic function of leukocytes isolated from ascorbic acid deficient guinea pigs. Glycolytic activity which provides the necessary energy for particle uptake was found to be decreased in both resting and phagocytizing leukocytes for ascorbic acid deficient guinea pigs. The direct oxidation of glucose through the hexose monophosphate shunt (HMS) was stimulated to a significantly lesser extent during phagocytosis in ascorbic acid deficient leukocytes. There was a progressive decline in phagocytosis induced shunt activity of leukocytes as the deficiency of ascorbic acid progressed. These findings show that particle uptake (as indicated by glycolytic activity) as well as particle destruction (as indicated by HMS activity) by leukocytes are impaired in ascorbic acid deficiency. Bactericidal capacity of leukocytes against Escherichia coli was also found to be low in ascorbic acid deficient guinea pigs as compared to those in the pair-fed control group.

Protein synthesis in zinc deficient rats during tularemia.

The effect of zinc deficiency on protein synthesis in rats during tularemia was studied. Five weeks prior to infection with the live vaccine strain of Francisella tularensis, rats had been assigned to one of three dietary groups: zinc deficient (-Zn), pair-fed (PF) or ad libitum (AL). Within 4 weeks, zinc deficiency manifested itself by diminished growth rate, decreased serum and liver zinc concentrations and alopecia. By 18 hour post infection, rats of all groups were febrile and exhibited an increased hepatic uptake of zinc. Despite initially lower concentrations of seromucoid in the PF and -Zn groups, infection elicited an increase in seromucoid concentration as well as enhanced incorporation of 3H-leucine into this fraction of comparable degree in all dietary groups. The same held true for ceruloplasmin. Alpha 2-macrofetoprotein also increased to the same extent in all dietary groups. Infection was associated with a decrease in extractable albumin in ad libitum and pair fed control groups. Only the -Zn group showed a significant decrease in specific activity suggestive of diminished albumin synthesis. Zinc deficiency of itself did not cause a decrement in radiolabel in muscle protein. Thus, despite documented zinc deficiency, rats subjected to the stress of infection respond by synthesizing increased amounts of acute phase globulins apparently at the expense of serum albumin and muscle protein synthesis.

Einfluß mangelnder Zinkversorgung auf Verdaulichkeit und Verwertung von Nährstoffen

Weaned male rats were used in a metabolic trial to investigate the digestibility of dry matter, crude protein, ash and energy, the energy and N balances and the rates of zinc absorption and zinc retention under conditions of zinc deficiency. 2X8 experimental animals were kept in separate metabolism cages for 6 periods each lasting 5 days. The animals received a semisynthetic zinc-deficient diet (casein + starch + sucrose) containing only 1.0 mg Zn per kg of dry matter (zinc-deficient group fed ad libitum) or plus 49 mg Zn per kg of dry matter (pair-fed control group). The mean intake of dry matter was 2-3 g per day/animal. 2.9 g of food were necessary to produce 1 g of weight increase in the deficient animals and 1.4 g in the controls. The rate of apparent zinc absorption was always clearly negative in the Zn-deficient group. In the control group apparent zinc absorption decreased from 60% to 27% in the course of the trial while zinc retention decreased from 51% to 10%. During zinc deficiency the rates of both faecal and absolute renal Zn excretion were found to be greatly reduced. The proportion of renal zinc excretion relative to total excretion averaged 60% in the experimental group as compared to 17% in the controls. No significant differences were found in the digestibility data of gross energy. Nutrient digestibility (%) was significantly reduced under conditions of Zn deficiency (data for the control group given in brackets): 92,6 (94.0) for dry matter; 93,2 (94.1) for organic matter; 93.3 (96.2) for crude protein and 76.6 (90.8) for crude ash. Similarly, N retention data, in Zn-deficient animals, declined from 30.5% to 14.7%, and metabolizable energy decreased from 88.7% to 85.6%. The differences obtained are not sufficient, however, to account for the clearly increased food requirements observed in zinc-deficient animals. Thus, considerable disturbances have to be assumed to occur in the processes of intermediary nutrient utilization.

Effect of zinc deficiency on glucose tolerance

18 male rats (Sprague Dawley) were divided into 3 groups each receiving the following amounts of dietary zinc: 2 mg/kg in the depletion group and 100 mg/kg in both the ad libitum-fed control group and in the pair-fed control group. After 34 days of experiment the rats were fasted for 12 hrs and then received 50 mg of glucose per 60 g of body weight injected into the femoral muscle. With equal intial glucose concentrations Zn-depleted rats exhibited a significantly reduce glucose tolerance compared with that of the ad libitum-fed control animals. The reduced glucose tolerance in the Zn-deficient animals does, in this case, not arise as a result of the reduced food intake and the resulting weakened condition of the animals. This was shown by results obtained with the pair-fed animals exhibiting a significantly more stable glucose tolerance than the Zn-depleted rats, which was even more rigid than that of the ad libitum-fed controls.

Carbonic anhydrase activity and erythrocyte count in the blood of zinc-deficient rats

Eighteen male Sprague Dawley rats were divided into three groups. They were offered a semisynthetic casein diet containing either 1.2 mg Zn/kg dry matter (depletion group) or 100 mg Zn/kg dry matter ( ad libitum and pair-fed control groups). At the beginning and on the 5th and 24th day of the experiment, blood was removed from a tail vein by incision to determine erythrocyte count and carbonic anhydrase activity. The zinc-depleted animals displayed a great increase in erythrocytes during the course of the experiment as compared to the ad libitum control animals. The erythrocyte counts of the pair-fed animals were also increased after 24 days on experiment, but remained significantly lower than those of the depleted animals. The activity of the carbonic anhydrase per ml blood was the same in all groups at the end of the experiment. When, however, the carbonic anhydrase activity was expressed per unit of erythrocytes, the zinc-deficient animals had a significantly lower enzyme activity than both the ad libitum and the pair-fed control rats.

Effect of Zinc Deficiency in Rats on Insulin Release from the Pancreas

To explain impaired intravenous glucose clearance in zinc-deficient rats, various parameters of insulin metabolism were measured. Three levels of dietary zinc were fed ( 1, 20, 1,200 ppm). To help distinguish between effects caused by zinc deficiency per se and inanition which accompanies zinc deficiency, a pair-fed control group (20 ppm) was included in some studies. Feeding of high or low zinc diets did not alter the insulin content of the pancreas, but immunoreactive serum insulin and total serum insulin-like activity measured by an in vitro adipose tissue assay were significantly reduced in the zinc-deficient group compared with ad libitum controls. The pair-fed control group also showed significantly reduced circulating immunoreactive insulin but not total serum insulin-like activity. High zinc diets did not affect serum insulin levels. In vitro studies of the release of pancreatic insulin during short incubation periods with glucose as a stimulant indicated that significantly less immunoreactive insulin as well as insulin-like activity was released by pancreata from zinc-deficient rats compared with pair-fed and ad libitum control rats. The pair-fed group, however, showed a significantly decreased release of pancreatic insulin compared with ad libitum-fed controls. Feeding of a high zinc diet did not affect the release of immunoreactive insulin but the release of total insulin-like activity was significantly increased above the ad libitum control value. The response of epididymal adipose tissue to insulin was significantly increased in zinc-deficient rats compared with ad libitum controls but not affected in rats fed the high zinc diet. J. Nutr. 103: 1739-1744, 1973.

The effect of chronic consumption of ethanol on the redox state of the rat liver.

Isocaloric replacement of the carbohydrate content of the diet by ethanol (36% of the total caloric intake) produced fatty infiltration and a reduced redox potential of the liver. The hepatic ratio of NAD+/NADH was 1.2 in the ethanol-treated group compared to 8.6 in the pair-fed control group. This change was associated with the consumption of ethanol as, 24 h after the removal of ethanol from the liver, the ratio had returned to the level of the control group. The hepatic substrate levels of NAD+-linked lactate dehydrogenase and the NAD+-linked β-hydroxybutyrate dehydrogenase systems were measured and used to calculate the NAD+/NADH ratio of the cytoplasm and mitochondria, respectively. The chronic consumption of ethanol did not alter the ratio in the cytoplasm but did shift the ratio in the mitochondria to one-fourth that observed in the control group. Twenty-four hours after ethanol was removed from the diet, this reduced redox potential in the mitochondria shifted to a level higher than that observed in the control groups.

Fatty Acid Metabolism in Rat Fed on Riboflavin Deficient Diet

An investigation has been attempted to clarify the metabolic fate of individual fatty acid in intact animals fed on the riboflavin deficient diet. Male rats of Wistar strain weighing 60 to 70g were divided into three groups; control group, riboflavin deficient group, and pair-fed control group for riboflavin deficient group. Six of riboflavin deficient rats were killed on the 10th, 20th and 30th day respectively after the deficient diet was given. Pair feeding was carried out for 30 days for riboflavin deficient rats which were sacrificed on the 30th day of deficiency.The results showed that there were no differences in weight, total fat content and fatty acid content in the liver between the deficient group and pair-fed control group. It may be due to the low dietary fat level used in this experiment that no fatty liver was seen in riboflavin deficient group. A significant decrease in the relative proportion of C16 to the botal fatty acid and a significant increase in the relative proportion of C18-2 were seen in the liver lipids of riboflavin deficient rats when compared with pair-fed control. These suggest that the changes in the relative proportion of C16-1, C18, C18-1 and C20-4 may not be due to riboflavin deficiency per se but may be due to lower calorie intake. Changes in serum fatty acid composition were almost similar to those of liver lipids, though there were two additional fatty acids, C16-1 and C18-1 whose relative proportion decreased in riboflavin deficiency.The foregoing results suggest that the impairments of linoleic acid and palmitic acid metabolism occur in riboflavin deficiency in the case of low dietary fat level.