The absorption, tissue distribution and excretion of enteraly administered alpha-ketoglutarate in rats

The absorption, tissue distribution and excretion of enteral alpha-ketoglutarate (AKG) was studied in four experiments. Six male Sprague Dawley rats were used to investigate the excretion of AKG in urine and faeces. Thirty rats, randomly assigned to five groups, were used to investigate the distribution of AKG in body tissues. They were gavaged with AKG enriched with 3 muCi/kg BW of (14)C uniformly marked AKG. Fourteen male Sprague Dawley rats were used to study the absorption of AKG (duodenum vs. ileum). Intestinal recovery of NaAKG vs. CaAKG was investigated in 36 rats. There was no significant excretion of non-metabolized AKG in the urine and faeces. There was no significant difference in the systemic levels of AKG when comparing the proximal to distal small intestine infusion. Up to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach, 0.5, 1 and 2 h after gavage; the jejunal recovery achieved a maximum of 3%, 30 min after gavage, and was not detectable 2 h later. There was a relatively high distribution of (14)C-AKG in the tissues (e.g. liver, brain, bones, skin, muscles), 3 h after gavage, up to 70% of the administered dose. In conclusion, the high rate of retention of the carbon from AKG allows the postulation that there is a non-energetic mode of metabolism of intragastrically administered AKG. After conversion to final metabolites, AKG penetrates into all tissues and organs of rats, including the bone tissue. Intestinal absorption of AKG does not depend on the type of AKG salt administered.     

Quantification of melamine absorption, distribution to tissues, and excretion by sheep

Eight D?hne Merino rams were used to quantify apparent absorption, distribution to tissues, and excretion of dietary melamine in sheep. Two batches of concentrate pellets were made; one (CON) contained corn gluten meal with no detectable melamine and the other (MEL) contained corn gluten meal that was previously found to be highly contaminated with melamine at 15,117 mg/kg. The MEL pellets contained 1,149 mg/kg of melamine. During a 10-d adaptation period, all the animals received a forage-based diet supplemented with 600 g/d of the CON pellets. This was followed by an 8-d collection period during which 6 of the animals received MEL pellets and 2 received CON pellets. Melamine intake of sheep that received MEL pellets was 0.69 g/d. Blood samples were taken before first ingestion of MEL pellets on d 1 and again on d 3, 6, and 8 of the collection period for melamine and serum creatinine analyses. Feces and urine were collected quantitatively over the 8 d for proximate and melamine analyses. All the animals were slaughtered at the end of the trial, and samples of the LM, liver, kidneys, and abdominal fat were taken for melamine analysis. Data of the 2 sheep that received CON pellets for the duration of the trial confirmed that no melamine was detected in any of the samples, and no statistical analyses were performed on these data. The apparent digestibility or efficiency of absorption of ingested melamine was 76.7%. Melamine was detected in the urine, blood, muscle (LM), and fat tissue of all the sheep that received MEL pellets. Serum melamine concentrations reached 5.4 mg/kg on d 8 of the collection period, and the meat (LM) contained 9.6 mg/kg of melamine. Calculations on the partitioning of ingested melamine suggested that urine is the major excretion route accounting for 53.2%, whereas feces accounted for 23.3% of ingested melamine. Approximately 3.5% of the ingested melamine was detected in muscle. It was concluded that ingested melamine is highly absorbable from the small intestine and that a pathway exists for the distribution of dietary melamine to meat.     

The absorption of anabolic agents from pellets implanted at the base of the ear in sheep

Twenty wether sheep were allocated to seven groups and received implants near the base of one ear with pellets containing: for group 1, (OE) 20 mg oestradiol-17 beta alone; for group 2, (TBA/OE) 20 mg oestradiol-17 beta intimately mixed with 140 mg trenbolone acetate; for group 3, (T/OE) 20 mg oestradiol-17 beta mixed with 200 mg testosterone; for group 4, (P/OE) 20 mg oestradiol-17 beta mixed with 200 mg progesterone; for group 5, (TBA/OE2) 20 mg oestradiol-17 beta in one ear and 140 mg trenbolone in the other ear; for group 6, (TBA/OE1) 20 mg oestradiol-17 beta and 140 mg trenbolone as separate pellets in one ear; group 7 sheep received implants of carrier material and served as controls. The concentrations of steroids were measured in plasma samples collected from both jugular veins during the 16-week period after implantation. The absorption of oestradiol-17 beta was slower and more sustained from the pellets in which it was mixed with other steroids (groups 2, 3 and 4) than from the pellets containing oestradiol-17 beta alone (groups 1, 5 and 6). The concentration of each steroid in plasma was higher in the jugular vein ipsilateral to the implant than in the vein on the opposite side. The difference between the concentrations in the two veins was used to calculate the biological half-lives of the steroids; for oestradiol-17 beta and trenbolone the mean values ranged from 1.8 to 6.8 min and from 3 to 4 min, respectively, and for testosterone and progesterone the mean values were 4.7 and 3.5 min, respectively.     

The effects of trienbolone acetate and other anabolic agents in growing turkeys

1. Very large increases in growth rates and improvements in the efficiency of food conversion of both male and female turkeys of 70 d of age or older were effected by the subcutaneous implantation of 20 to 40 mg of trienbolone acetate (TA). 2. Implantation of TA (10 to 40 mg) into turkeys of 42 d of age or less caused growth depression, usually following an initial period of positive growth response. 3. During the period of growth depression, food conversion efficiency deteriorated and treated turkeys developed chondrodystrophic skeletal abnormalities and/or "leg weakness". 4. Implantation of oestradiol and of testosterone into 2-d-old turkeys also led to the development of skeletal abnormalities. 5. Implantation of testosterone (25 mg) into 84-d-old stag turkeys produced positive growth responses which were of smaller magnitude and lesser duration than those produced by TA. 6. Implantation of 70-d-old stag turkeys with a combination of TA (20 mg) and hexoestrol (15 mg) resulted in performances which were slightly superior in terms of the growth to those following administration of TA alone but which were markedly inferior in respect of food conversion.     

Metabolism of endogenous and exogenous anabolic agents in cattle

The endogenous anabolic agents, estradiol-17 beta, progesterone and testosterone are steroids that are quickly metabolized by the liver and are not very active when administered orally. Estradiol-17 beta is excreted by the bovine in bile as free estradiol-17 alpha, and by swine, in urine, as glucuronides and sulfates. In ruminants, the primary metabolite of progesterone is pregnandiol and that of testosterone is epitestosterone. In horses, the metabolites of these compounds are primarily 17 ketosteroids. Esters of the endogenous anabolic agents are rapidly hydrolyzed and the nonesterified forms follow the same biotransformation pathways as the natural compounds biosynthesized by the animal. The exogenous anabolic agents, such as trenbolone acetate, zeranol and diethylstilbestrol, may be active by the oral route and are less readily metabolized in the liver than the endogenous anabolics. Their metabolic pathways may be complex and lead to excreted forms after glucuronide conjugation. With respect to biochemical mechanism of action, it can be assumed that the anabolics act like all steroids by way of intracellular receptors. Biotransformations could lead to more reactive molecules that may bind themselves to normal constituents of the organism. Bound metabolites are generally formed later than free metabolites, and are considered less toxic with a lower level of bioavailability.     

Protein metabolism in animals treated with anabolic agents

One of the major factors controlling the deposition of protein in an animal is the activity of the hormones circulating in its blood. Many of the anabolic hormones interact with each other e.g. growth hormone and insulin and there is evidence for a direct interaction between catabolic and anabolic hormones e.g. testosterone and glucocorticoids. Exogenously administered hormone-like substances can have marked effects on animal growth. Diethyl stilbestrol acts like an oestrogen elevating plasma insulin and growth hormone concentration. Zeranol probably also acts in a similar way.Trenbolone acetate (TBA) an androgenic agent, is a very effective growth promotor especially in ruminants. Few changes of note in the endogenous plasma hormone concentrations in treated ruminants have been reported although the combined implant of TBA plus 17-oestradiol did depress plasma thyroxine in steers. We have used the rat as a model to test the effects of TBA on protein synthesis and protein degradation rate in the muscle of rats. Protein synthesis and protein degradation in the muscle of treated female rats was shown to be markedly reduced, the increased growth rate being brought about by a greater reduction in the rate of degradation than in the rate of synthesis. Cathepsin D activity in the muscle was also reduced. Attempts to demonstrate a direct action of TBA on muscle have been unsuccessful. The currently favoured hypothesis for the mode of action of TBA is that it interferes with catabolic action of glucocorticoids on muscle protein. This may not be the mode of action of all androgenic agents. Durabolin (nandrolone phenyl propionate) would appear to stimulate both protein synthesis and protein degradation, at least in the rat.     

Absorption, distribution, and excretion of imidocarb dipropionate in sheep

Spectrophotometric and thin-layer chromatographic methods for determination of imidocarb in biological specimens are described. Following intravenous injection of imidocarb (2.0 mg/kg) into 3 sheep, plasma concentrations, initially averaging 10.8 microgram/ml, decreased to an average of 1.9 microgram/ml within 1 hour and then to less than 1 microgram/ml within the next 4 hours. When imidocarb (4.5 mg/kg) was injected intramuscularly (IM) into 7 sheep, peak plasma concentrations averaging 7.9 microgram/ml were achieved within 4 hours and then rapidly decreased to 4.6 microgram/ml within the next 2 hours. Plasma values then decayed very slowly by first-order kinetics and trace amounts were still present 4 weeks after treatment. Imidocarb was bound to plasma proteins and the apparent volume of distribution was estimated to be slightly higher than the total body water. The concentrations of the drug in the plasma and in the erythrocytes were approximately equal. Detectable amounts were present in all examined tissues 4 weeks after IM administration Twenty-four hours after IM administration, the highest concentrations were in kidney, liver, and brain. The 14C-labeled imidocarb could be detected in all regions of the central nervous system examined, in the hypophysis, and in the pineal body. Metabolic or biotransformation products were not detected by the methods used. Of the administered IM dose, 11 to 17% was excreted in the urine within 24 hours; thereafter, the excretion rate was low, and detectable amounts were still present in the urine for 4 weeks. Renal clearance of imidocarb was less than glomerular filtration rate, indicating net tubular reabsorption. The relatively high concentration of imidocarb in the bile suggests that the bile is an important route of excretion. High concentrations were also found in the mild of lactating ewes, but the drug could not be detected in the plasma of lambs fed milk from these ewes.     

Absorption, distribution, metabolism, and excretion of dirlotapide in the dog

Three once-daily oral doses of 0.2 mg/kg [¹⁴C]dirlotapide were administered to beagle dogs to study the absorption, distribution, metabolism, and excretion of dirlotapide. Mean ¹⁴C recovered at 2.5 and 4.5 h after the last dose was 90%. Mean ¹⁴C in urine, bile, and feces was <1%, 1.7%, and 56% of the dose, respectively. In tissues, 26% of the ¹⁴C dose was present in the gastrointestinal tract, 6.0% in liver, and <1% each in kidney, gall bladder, heart, and brain. To further characterize drug disposition, a single 2.5-mg/kg oral dose of [¹⁴C]dirlotapide was administered to beagle dogs. More than 84% of the dose had been eliminated by 72 h in feces, with 21% of the dose present in feces as parent dirlotapide. Less than 1% of the dose was excreted in urine. In bile collected during the first 24-h postdose from three dogs, 32% and 11% of the ¹⁴C dose was present in samples from male and female dogs, respectively. Based upon metabolite profiling of plasma, excreta, and bile samples, dirlotapide was extensively metabolized to more than 20 metabolites. Biliary/fecal excretion and the potential for enterohepatic recycling of metabolites are suggested.     

Reduced growth of calves and its reversal by use of anabolic agents

Disease has profound effects on the immune system, endocrine system, and on the growth process. Since diseases are catabolic to the animal, there is current interest in the possible role of anabolic hormones to counter the effects of disease in general and minimize the effects of a disease process on growth and development. A number of anabolic hormones, such as growth hormone (GH) and estradiol + progesterone (EP), have been studied for their role in enhancing growth and stimulating immune function and are thus candidates for hormonal intervention in disease processes. GH has been shown to be effective in countering some of the deleterious effects of endotoxemia but was ineffective in a parasitic disease model. Studies with EP have shown similar success with both endotoxemia and a parasitic disease model. Moreover, GH and EP do not share a common mechanism of action, suggesting that the effects are not simply due to anabolic actions. While the mechanism of action of GH in endotoxemia has been examined, the effects of EP are via an unknown mechanism, possibly by inhibition of IL-I action or inhibition of nitric oxide overproduction.     

The effects of anabolic agents and breed on the fibers of the longissimus muscle of male cattle

Sample of longissimus muscle were taken from carcasses of steers, steers implanted with anabolic agents and bulls of Friesian and Charolais X Friesian breeds of cattle. Percent and mean cross-sectional areas (CSA) of three myofiber types (beta R, alpha R and alpha W) were determined. The percentage of beta R myofibers did not vary significantly with treatment. The implanted steers had 26% more alpha R and 8% less alpha W myofibers than the untreated steers, while the bulls had 33% more alpha R and 20% less alpha W myofibers than the implanted steers (P less than .001). In the implanted steers the mean CSA of the beta R myofibers was significantly greater than that of the untreated steers, but did not differ from that of the bull. The mean CSA of the alpha R myofibers increased considerably with treatment, but only that of the bull was significantly greater than that of the untreated steers. The mean CSA of the alpha W myofibers in the implanted steers was identical with that of the untreated steers and significantly smaller than that of the bulls. In comparison to the untreated steers, significant hypertrophy of all three myofiber types occurred in bulls. These findings demonstrate a significant increase in the oxidative capacity of the longissimus when the levels of both endogenous and exogenous anabolic agents are increased. They are also consistent with the greater efficiency of deposition of protein obtained with implanted steers and bulls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of repeated implantation with anabolic agents on growth rate, carcase weight, testicular size and behaviour of bulls

The effects of implantation with different anabolic agents on growth rate, behaviour, carcase parameters and testicular size of bulls were evaluated in an experiment with 361 Friesian bulls about three months old on three farms. Animals were allocated to one of the following treatments: (a) Control; (b) repeated implantation with 36 mg zeranol at intervals of 95 to 124 days; (c) repeated implantation with 20 mg oestradiol benzoate plus 140 mg trenbolone acetate as in (b); (d) repeated implantation with 20 mg oestradiol benzoate plus 200 mg progesterone as in (b); (e) implanted once with 45 mg oestradiol-17 beta. Daily liveweight gain, carcase weight, testicular size and behaviour of the animals were the parameters measured. Repeated implantation of young bulls with hormones, beginning at eight to 10 weeks old, increases liveweight gain and carcase weight from 0 to 15 per cent, reduces aggressive behaviour and testicular size and, in some instances, improves conformation and increases fat cover of the carcase.     

Dietary isoflavone absorption, excretion, and metabolism in captive cheetahs (Acinonyx jubatus)

Dietary isoflavones, capable of influencing reproductive parameters in domestic cats (Felis catus), have been detected in commercial diets fed to captive cheetahs (Acinonyx jubatus). However, the absorptive and metabolic capacity of cheetahs towards isoflavones has not yet been studied. Experiments were designed to describe the plasma concentration-time curve, metabolite profile, and urinary and fecal excretion of genistein and daidzein in cheetahs following consumption of isoflavones. Four adult cheetahs were administered a single oral bolus of genistein and daidzein, and five juvenile cheetahs consuming a milk replacer formula found to contain isoflavones were also included. Urine was collected from all animals, and blood and feces were also collected from adult cheetahs following isoflavone exposure. Samples were analyzed for isoflavone metabolite concentration by liquid chromatography-electrospray ionization-multiple reaction ion monitoring mass spectrometry and high-performance liquid chromatography. Sulfate conjugates were the primary metabolites detected of both genistein and daidzein (60-80% of total isoflavones present) in the plasma and urine of cheetahs. A smaller proportion of daidzein was detected as conjugates in the urine of juvenile cheetahs, compared to adult cheetahs. Other metabolites included unconjugated genistein and daidzein, O-desmethylangolensin, and dihydrodaidzein, but not equol. Only 33% of the ingested genistein dose, and 9% of daidzein, was detected in plasma from adult cheetahs. However, of the ingested dose, 67% of genistein and 45% of daidzein were detected in the feces of adults. This study revealed that cheetahs appear efficient in their conjugation of absorbed dietary isoflavones and only a small fraction of ingested dose is absorbed. However, the capacity of the cheetah to conjugate genistein and daidzein with sulfate moieties appears lower than reported in the domestic cat. This may confer greater opportunity for biologic activity of isoflavones in the cheetah than would be predicted from findings in the domestic cat. However, further investigation is required.     

The absorption and excretion of minerals by laying hens in relation to egg shell formation

The absorption and urinary and faecal excretion of calcium, phosphorus, magnesium, sodium, potassium and chloride were studied in four colostomised laying hens during 24 hr periods. The urinary excretion of ammonia was also determined. Data for 10 laying and 5 non‐laying days were obtained. On laying days (a) net absorption of all minerals, expressed either as actual weights or as a percentage of intake was greater, (b) urinary excretion of phosphorus, potassium and ammonia was greater and of calcium, magnesium and chloride less and (c) retention of all minerals was greater, than on non‐laying days.

The urinary findings can be largely explained in terms of the requirements of the shell gland for calcium and bicarbonate ions and the need to excrete the phosphate liberated from the skeleton during egg shell formation.