Evaluation of allopurinol as a cardioprotectant in ethanol-fed turkey poults

Cardioprotectant effects of allopurinol were investigated in ethanol-fed poults during induction of cardiomyopathy and during a period of ethanol abstinence. In young poults fed ethanol, allopurinol has an additive effect on depression of growth but has little or no effect on caloric consumption. Allopurinol significantly depresses heart weight and heart weight to body weight ratios in young poults. In poults 5 weeks and older, allopurinol depresses significantly body weight and caloric consumption. Although allopurinol depresses heart weight in older poults, it appears to have little or no effect on heart weight to body weight ratios. Cardioprotective effect of allopurinol is more apparent during the inductive process than during the recovery phase.     

Plasma uric acid levels in ethanol-fed turkey poults treated with allopurinol

Plasma uric acid levels were determined in ethanol-fed poults following administration of allopurinol. In young poults, allopurinol at a dose of 50 mg/kg significantly depressed plasma uric acid levels 6 hr post-dosing. At 11 hr post-dosing, plasma uric acid levels were significantly elevated in the allopurinol-treated poults when compared with control poults. During a period of ethanol abstinence, allopurinol at a dose of 40 mg/kg significantly depressed plasma uric acid levels up to 8 hr post-dosing. At a dose of 30 mg/kg, plasma uric acid levels were similar to control values at 4 and 6 hr post-dosing. Data suggest that plasma uric acid levels can be depressed in ethanol poults when allopurinol is administered every 8 hr at a dose of 40-50 mg/kg of body weight.     

Dietary carbohydrate effects on some plasma organic acids and aspects of glucose metabolism in turkey poults

The effects on newly-hatched turkey poults of feeding diets with varying levels of carbohydrate and of oral gavage with suspensions of corn starch were studied. Feeding lowered hepatic glucose-6-phosphatase activity and raised blood glucose and hepatic glycogen concentrations. In Nicholas strain turkeys, increases of dietary levels of carbohydrate enhanced hepatic glycogen stores without affecting blood glucose concentration or glucose-6-phosphatase activity. Oral gavage of poults with suspensions of corn starch in water raised blood glucose and hepatic glycogen concentrations and lowered glucose-6-phosphatase activity in dose- and time-dependent manners. Changes were noted at 1 hr post-gavage. Oral gavage with starch lowered lactate concentrations in muscle and plasma and lowered plasma concentrations of β-hydroxybutyrate and urate. Plasma concentrations of pyruvate appeared to decline with post-hatch holding without feed. Thus, the apparent effect of starch gavage on plasma pyruvate (high concentration) is dependent upon the length of the holding period for the controls. The data show that poults can alter their metabolism (decrease lipid oxidation and gluconeogenesis and increase carbohydrate stores) almost immediately (1 hr) after oral administration of carbohydrate.     

Effects of stressors on blood glucose and hepatic glycogen concentrations in turkey poults.

1. The putatively stressful procedures of sexing, toe trimming, snood removal, beak trimming and injection of antibiotic solution, as performed in a commercial hatchery, elevated blood glucose levels and depressed hepatic glycogen levels in newly-hatched turkey poults. 2. The first procedure performed, cloacal sexing, was sufficient to elevate blood glucose, but all procedures were required before depression of hepatic glycogen occurred. 3. Blood glucose levels declined in both untreated (INITIAL) and fully-treated (FINAL) poults over a 24 hr holding period. 4. Hepatic glycogen declined with 24 hr holding of INITIAL poults but increased with holding of FINAL poults.     

Contractile function, glucose consumption and lactate release by the isolated rat heart during different regimens of alcohol administration and after discontinuation of ethanol

Acute or chronic intoxication of rats with ethanol (intragastric administration at a dose of 8 g/kg or free-choice drinking of 10% ethanol for 3 months) produced no significant changes in contractile function, glycogen content, glucose uptake and lactate release in isolated hearts. Withdrawal syndrome simulated in rats following a short period of severe intoxication with ethanol at a dose of 4-5 g/kg twice daily has demonstrated a 15 and 28% decrease in peak systolic pressure and tension time index, respectively. In this case glucose uptake and lactate release were 2 times higher. Changes in glycogen level were observed three days after the last ethanol administration. The rats, survived after the abstinence period, revealed areas of perivascular myocardial necrosis. It is concluded that withdrawal syndrome plays an important role in pathogenesis of alcoholic cardiomyopathy.     

Myocardial calcium levels in furazolidone-induced cardiomyopathy in turkey poults

Myocardial calcium levels were measured in control turkey poults and in poults with furazolidone (FZ)-induced cardiomyopathy. FZ at a dose of 700 ppm added to the feed of poults from 2 to 5 weeks post-hatching produced the typical round-heart syndrome but had little effect on the calcium levels in the myocardium. Data suggest that the mechanism of FZ cardiotoxicity is not associated with calcium overload.     

Effects of oxytetracycline treatment on enzymes of hepatic glycogen metabolism in genetically diabetic (db/db) mice

The effects of daily oxytetracycline treatment on the activities of hepatic glycogen synthase, glycogen phosphorylase, plasma glucose, and insulin, and on liver glycogen, free fatty acid, and triglyceride levels were examined in 8- to 15-week-old genetically diabetic and lean mice. Oxytetracycline administration resulted in substantial reductions in the plasma glucose and immunoreactive-insulin levels in both diabetic and lean mice. The drug had no significant effect on the liver glycogen content in either phenotype, regardless of age, but it increased hepatic lipids and depressed body weights in lean animals. The most prominent effect of the drug was in markedly altering the activities of both glycogen synthase and phosphorylase in the liver of older diabetic mice. Oxytetracycline treatment produced a three-fold increase in the percentage of glycogen synthase I activity and reduced by one-third the percentage of glycogen phosphorylase a activity in 15-week-old diabetic mice. In age-matched lean mice treated with oxytetracycline, the percentage of glycogen synthase I activity increased significantly, but the percentage of phosphorylase a activity was unchanged. These data suggest that the drug may alter an aspect of hepatic glycogen metabolism which might lead to an inhibition of glycogenolysis and subsequent diminution of blood sugar levels in the diabetic. The present results show that, while oxytetracycline may be effective in reducing the severity of some of the diabetic symptoms associated with carbohydrate metabolism in this animal model of maturity-onset diabetes, the drug may have adverse effects on aspects of protein and lipid metabolism in these animals.     

Diurnal changes in the glucose and glycogen levels of the blood and liver of rats in chronic consumption of alcohol and after its withdrawal

Chronic ethanol ingestion by rats exerts almost no effect on the diurnal rhythms of the blood and hepatic glucose concentrations. The rhythm of liver glycogen alters substantially in ethanol-fed animals, the phase of the rhythm being shifted and the daily mean level of glycogen being reduced by a factor of 2. Much more drastic disturbances in carbohydrate metabolism occur after ethanol withdrawal than with ethanol consumption. The diurnal rhythm of liver glycogen becomes inverted in phasing, and the rhythmic amplitude reduced greatly as compared with controls. Both the blood and hepatic glucose concentrations are maintained at nearly constant levels for 18-21 h after ethanol withdrawal, but then the level of blood glucose sharply falls, while that of hepatic glucose somewhat increases. The liver cytosolic water/blood plasma water gradient of glucose 24 h after ethanol withdrawal achieves a value of 4 and remains low 24 h later. The liver glycogen level remains relatively high over the 24 h period after ethanol withdrawal despite the severe hypoglycemia, that can be a result of a limitation of the liver cell membrane permeability for glucose.     

Ultrastructural features of ethanol-induced cardiomyopathy in turkey poults

Alcoholic cardiomyopathy, characterized by cardiac hypertrophy, was induced in young turkey poults with 5% ethanol. Ultrastructural features included accumulation of glycogen, swollen mitochondria, myofibrillar lysis, increased number of lysosomes, dilated sarcoplasmic reticulum and dense myofibers. Similarity of these alterations to those described in human alcoholic cardiomyopathy confirms the usefulness of the turkey poult as an animal model for this disease syndrome.     

Metabolic effects of ethanol in the rat liver.

The NADPH is one of the cofactors in ethanol metabolism. The aim of the study was to investigate the effect of ethanol on a NADPH generating enzyme (G6P-DH) and on some metabolic parameters of the liver. After a 2-day starvation period rats were fed a lipid free diet for three days. During this refeeding period the animals were divided into three groups; they received a single daily dose of 4 g per kg b.w. ethanol, isocaloric aqueous glucose solution or water by gastric tube. In response to ethanol the activity of hepatic G6P-DH decreased. The amount of triglyceride remained unchanged, certain changes occurred in the fatty acid composition of total lipid. The liver glycogen content was elevated. In female rats treated with ethanol the activity of glucose-6-phosphatase increased.     

Enzyme activity of cardiac glycogen metabolism: study of an in situ hypoxia protocol in the rat

Myocardial hypoxia, induced by arrest of the artificial ventilation of anaesthetized open-chest rats, was utilized in order to study some aspects of the regulation of myocardial glycogen metabolism. Atenolol, a cardioselective beta-adrenergic receptor antagonist, and verapamil, an inhibitor of sarcolemmal calcium transfer, were used to determine the respective role of adenosine 3', 5'-cyclic monophosphate (cAMP) and calcium in the activation of the enzymes of glycogen phosphorolysis and synthesis. Glycogen degradation is reduced by atenolol treatment, as a consequence of a reduced activation of glycogen phosphorylase. Verapamil treatment has no significant effect, neither on the enzyme activation nor on the glycogen utilization. The activation of glycogen synthase, expressed by the conversion of the enzyme from the D to the I form, which results from the decrease in glycogen stores during hypoxia, is lowered under the effect of both drugs. However, in the beta-blocker treatment case, this effect results from a lower glycogen depletion while this effect is more specific in hearts from rats treated with verapamil. Under the effect of verapamil, the reduction of synthase activation, for a similar depletion of glycogen stores, was confirmed by experiments using isolated rat hearts submitted to ischaemia. These results show that: 1. the glycogenolysis in the hypoxic myocardium in situ is mainly controlled by a cAMP-dependent enzyme conversion or by metabolic allosteric effectors; 2. the activation of myocardial glycogen synthase, which is essentially correlated to the reduction of glycogen stores, is also calcium-dependent and most probably totally cAMP-independent.     

Plasma prolactin levels in incubating turkey hens during pipping of the eggs and after introduction of poults into the nest

Plasma levels of prolactin (Prl) associated with incubation and maternal behavior were compared in turkey hens allowed to incubate 10 fertile eggs (Group I, n = 9) or 10 infertile eggs (Group II, n = 7) in open nest boxes. At the end of the day that the first egg hatched, all unhatched eggs were removed from Group I hens and each hen was given 10 poults. At the end of the following day, infertile eggs were removed from Group II hens and each hen was given 10 poults. Although pipping of the eggs changed the incubation behavior of Group I hens, it had no effect on plasma Prl. Subsequent hatch of the eggs and/or presence of poults resulted, within 24 h, in a sharp fall in Prl levels, abandonment of the nests, and a shift to maternal behavior. Visual and auditory exposure to Group I poults had no effect on plasma Prl or incubation behavior of Group II hens incubating infertile eggs in adjacent pens. However, within 24 h after the infertile eggs were exchanged for newly hatched poults, Prl levels in Group II hens declined sharply and the hens abandoned the nests and showed maternal behavior similar to that observed in Group I hens. No significant relationships were found in either group between plasma Prl levels and quality of incubation or maternal behavior.     

Liver glycogen and plasma insulin and glucagon levels in food- and water-deprived black-tailed prairie dogs (Cynomys ludovicianus)

1. Liver glycogen levels and plasma levels of insulin and glucagon were measured in fed and in food- and water-deprived prairie dogs. 2. Liver glycogen values decreased from 45.5 to 12.4 mg/g (73%) after 21 days of food and water deprivation, while a 24-hr fast resulted in a liver glycogen value of 47.5 mg/g. 3. Rat liver glycogen values decreased from 45.6 to 2.3 mg/g (95%) after a 24-hr fast. 4. Prairie dog plasma insulin values were 69.2, 15.8 and 25.4 microU/ml in fed, and in 24-hr and 32-day food- and water-deprived animals, respectively. 5. Prairie dog plasma glucagon levels were 57.0 and 38.4 microU/ml in fed and in 32-day food- and water-deprived animals. 6. Plasma values for glucose, urea nitrogen, acetone and triglyceride agreed with previously published results. 7. We conclude that it is possible that the maintenance of liver glycogen levels in food- and water-deprived prairie dogs may be correlated with a smaller decrease in plasma insulin levels, relative to other species, and with a decrease in plasma glucagon levels.     

Regulation of glycogen concentration and glycogen synthase activity in skeletal muscle of insulin-resistant rats

The aim of this study was to investigate the effect of insulin resistance on glycogen concentration and glycogen synthase activity in the red and white gastrocnemius muscles and to determine whether the inverse relationship existing between glycogen concentration and enzyme activity is maintained in insulin resistant state. These questions were addressed using 3 models that induce various degrees of insulin resistance: sucrose feeding, dexamethasone administration, and a combination of both treatments (dex+sucrose). Sucrose feeding raised triglyceride levels without affecting plasma glucose or insulin concentrations whereas dexamethasone and dex+sucrose provoked severe hyperinsulinemia, hyperglycemia and hypertriglyceridemia. Sucrose feeding did not alter muscle glycogen concentration but provoked a small reduction in the glycogen synthase activity ratio (-/+ glucose-6-phosphate) in red but not in white gastrocnemius. Dexamethasone administration augmented glycogen concentration and reduced glycogen synthase activity ratio in both muscle fiber types. In contrast, dex+sucrose animals showed decreased muscle glycogen concentration compared to dexamethasone group, leading to levels similar to those of control animals. This was associated with lower glycogen synthase activity compared to control animals leading to levels comparable to those of dexamethasone-treated animals. Thus, in dex+sucrose animals, the inverse relationship observed between glycogen levels and glycogen synthase activity was not maintained, suggesting that factors other than the glycogen concentration modulate the enzyme's activity. In conclusion, while insulin resistance was associated with a reduced glycogen synthase activity ratio, we found no correlation between muscle glycogen concentration and insulin resistance. Furthermore, our results suggest that sucrose treatment may modulate dexamethasone action in skeletal muscle.     

Characterization of glycogen in selected tissues of turkey poults with spontaneous round heart disease and furazolidone-induced cardiomyopathy.

Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults 2--5 weeks after hatching to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From EKG data obtained at weekly intervals, poults were selected for sacrifice at 5 and 10 weeks of age. Poults were sacrificed by cervical dislocation and appropriate samples of tissue from the left ventricle, liver, pectoralis and tibialis cranialis muscles were removed for glycogen assays. Character of glycogen, as determined by percent of branching and number of glucose units per segment, was not significantly altered in poults with spontaneous round heart disease or FZ-induced cardiomyopathy. This suggests that the glycogen accumulation noted in these conditions most closely resembles type II glycogenosis.     

Biochemical aspects associated with an ethanol-induced fatty liver

Isocaloric replacement of either the fat or carbohydrate content of the diet by ethanol (36% of the total caloric intake) produced fatty infiltration of the liver in rats. The increase in hepatic triglyceride content was associated with a decrease in both ATP and glycogen contents. Increased activity of mitochondrial Mg(2+)-stimulated adenosine triphosphatase paralleled the increase in the free P(i) content of the liver homogenate. During the regression of the fatty liver, glycogen contents returned to normal within 24h of the removal of ethanol from the diet. Not until the third day after the withdrawal of ethanol had the Mg(2+)-stimulated adenosine triphosphatase activity and free P(i) content of the homogenate returned to normal. A slow regression of the triglyceride content from the liver occurred and by the fifth day both ATP and triglyceride concentrations had returned to the values observed in the rats given the liquid control diet.     

Effect of ethanol on certain metabolic pathways in young R/Amsterdam rats

R/Amsterdam rats were offered a 15% aqueous ethanol solution as drinking fluid from delivery via the milk (Group A) or from the weanling (Group B). Ethanol treatment resulted in a significant retardation of growth in both Groups A and B compared to controls (Group C); the changes were more marked in Group A. Female rats responded to ethanol with higher increase of microsomal G6P-ase and mixed function oxygenase activities than males subjected to the same treatment. Hepatic triglyceride, glycogen and protein contents remained unaffected by ethanol. There was no difference in the changes of liver metabolism between Groups A and B either receiving ethanol already from birth via the milk or only after weanling.     

Morphine dependent rats: Blockade of precipitated abstinence by calcium

In rats made dependent on morphine, brain levels of calcium were significantly lowered. Naloxone administration to such rats produced characteristic abstinence signs. Prior treatment with calcium markedly reduced naloxone-induced abstinence signs and prevented morphine-induced lowering of brain calcium. It is suggested that the antagonistic actions of calcium and morphine may be related to their effects on morphine-sensitive adenylate cyclase activity.     

Variations of two pools of glycogen and carbohydrate in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> grown with various ethanol concentrations

Glycogen, a major reservoir of energy in Saccharomyces cerevisiae, is found to be present as soluble and membrane-bound insoluble pools. Yeast cells can store excess glycogen when grown in media with higher concentration of sugar or when subjected to nutritional stress conditions. Saccharomyces cerevisiae NCIM-3300 was grown in media having ethanol concentrations up to 12% (v/v). The effects of externally added ethanol on glycogen and other carbohydrate content of yeast were studied by using alkali digestion process. Fermentative activities of cells grown in the presence of various ethanol concentrations (2–8% v/v) exhibited increase in values of glycogen and other carbohydrate, whereas cells grown with higher concentrations of ethanol (10–12% v/v) exhibited depletion in glycogen and carbohydrate content along with decrease in cell weight. Such inhibitory effect of ethanol was also exhibited in terms of reduction in total cell count of yeast grown in media with 2–16% (v/v) ethanol and 8% (w/v) sugar. These data suggest that, as the plasma membrane is a prime target for ethanol action, membrane-bound insoluble glycogen might play a protective role in combating ethanol stress. Elevated level of cell-surface α-glucans in yeast grown with ethanol, as measured by using amyloglucosidase treatment, confirms the correlation between ethanol and glycogen.     

Effect of an exercise run to exhaustion on cAMP in the rat heart

The purpose of this investigation was to determine whether adenosine 3',5'-cyclic monophosphate (cAMP) content is increased in vivo in the heart as a result of exercise at a time when there is rapid cardiac glycogen utilization. Rats were run to exhaustion on a treadmill for a period of 164.5 +/- 9.5 min. Blood norepinephrine and epinephrine were significantly elevated approximately 2.5-fold above resting levels at the end of the treadmill run. Myocardial glycogen was reduced by 54.7% at exhaustion compared with control values. Myocardial cAMP was significantly elevated 88% above control levels as a result of the run. Associated with the depletion of myocardial glycogen and the elevation of cAMP was an activation of phosphorylase to its a form. These data suggest that myocardial glycogen metabolism during exercise is, in part, mediated by hormonal influences that are associated with increases in cAMP.