Effects of aluminum chloride on normal and uremic adult male rats

Normal and uremic adult male rats were given a daily ip injection of 20 mg Al (Al chloride)/kg for 14 d. The results indicate that Al induces a significant decrease in food ingestion, weight gain, and total protein concentration in the plasma. Compared with control animals, very high increases in Al levels were found in plasma and hepatic homogenates (about 36 and 19 times, respectively). In the brain homogenates, the Al increases were lower (about 23%). The brain cholineacetyltransferase activity was reduced: 10.6 and 14.9% in normal and uremic rats, respectively. The nephrectomy and the food restriction did not affect the total protein concentrations in plasma and the cerebral cholineacetyltransferase activity. Both were only found to be reduced in the rats treated by Al chloride.     

Dietary tyrosine supplementation enhances weight gain in streptozotocin-diabetic rats

The effect of dietary protein concentration and tyrosine supplementation on growth in streptozotocin (65 mg/kg, ip) diabetic rats was evaluated. When rats were fed diets ranging from 15 to 60% protein, weight gain and feed efficiency were greatest in rats fed the 45% protein diet. Adding tyrosine to this diet (8%, incorporated as a percentage of protein) did not promote further weight gain relative to nonsupplemented diabetic animals. In contrast, rats choosing 45% of total calories as protein by selecting from 10 and 60% protein diets supplemented with either 0, 4, or 8% tyrosine demonstrated a 35% (4% tyrosine) to 45% (8% tyrosine) increase in weight gain. Proximate analysis indicated similar body composition in tyrosine supplemented and nonsupplemented diabetic animals. Including tryptophan (1.45%) with tyrosine in the self-selection diet was without effect. Thus, tyrosine supplementation promoted a modest but consistent and specific increase in weight gained by self-selecting diabetic rats.     

Effect of increased dietary calcium on body weight, food and water intake in oral contraceptive treated female rats

The effects of high calcium diet on body weight in OC treated rats are unknown. This study therefore investigated the effect of increasing dietary calcium from 0.9% to 2.5% on body weight, food ingestion, water intake, heart weight index and renal weight index in female Sprague-Dawley rats treated with a combination of OC steroids (ethinyloestradiol + norgestrel). The rats were assigned into three groups of average of 11 rats each; control, OC-treated and OC + Calcium – treated groups and administered orally for 10 weeks. Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats. The OC + Calcium – treated rat had significantly higher serum calcium concentration, food, water and calcium intake but significantly lower body weight than those of the OC - treated rats. OC + Calcium - treated rats had significantly higher water intake, calcium intake and significantly lower body weight and food intake when compared with the control rats. Cardiac weight index and renal weight index was comparable in all groups. In conclusion, combined OC-induced reduction in weight gain might be associated with inhibition of the feeding center and consequent inhibition of the thirst center. Co-administration of dietary calcium augmented the reduction in weight gain seen in OC-treated rats probably by further suppression of the feeding and thirst centers.     

Administration of bovine anti-IGF-1 immunoglobulin to dietary protein deficient rats alters dietary intake and plasma IGF-1 binding profiles, but does not affect change in body mass

The potential of antibodies raised against insulin-like growth factor-1 (IGF-1) as a treatment to enhance the anabolic actions of IGF-1 has been demonstrated in both rodent and ruminant models. We investigated whether treatment of genetically normal rats with anti-IGF-1 immunoglobulin (Ig, raised in cattle) would enhance growth and if anti-IGF-1 Ig treatment would ameliorate live-weight loss in genetically normal rats offered a severely protein-restricted diet. Scatchard analysis was used to characterise ammonium sulphate precipitated bovine anti-IGF-1 Ig. Anti-IGF-1 Ig binding to 125I-IGF-1 yielded an almost linear Scatchard plot, with a Hill co-efficient of 0.951 ± 0.012, indicating a single class of IGF-1 binding sites. The affinity of anti-IGF-1 Ig for IGF-1 was 2.14 ± 0.66 × 109 l/mol. The non-immune Ig preparation did not bind IGF-1. Rats were offered either a diet with a normal protein level (20%) or protein restricted (4% protein), and each dietary group was further treated with twice-daily i.p. injections of either diluent phosphate buffered saline, non-immune Ig or anti-IGF-1 Ig. Dietary protein level had a significant effect on live-weight gain, but there was no effect of non-immune Ig or anti-IGF-1 Ig on live-weight gain. Treatment with anti-IGF-1 Ig prevented the significant depression of cumulative dietary intake observed in diluent, and non-immune Ig treated groups offered the 4% protein diet. The cumulative dietary intake of the anti-IGF-1 Ig treated, 4% dietary protein group did not differ significantly from those of the groups offered the 20% protein diet. In addition, within the 4% dietary protein group, rats treated with non-immune Ig exhibited a cumulative feed intake that was intermediate between that of the diluent treated and anti-IGF-1 Ig treated groups (P < 0.05). Size exclusion chromatography was used to characterise in vitro 125I-IGF-1 binding in end-point plasma from each treatment group. In comparison to control groups, anti-IGF-1 Ig treatment resulted in substantially increased 125I-IGF-1 binding in the 30 to 40 kDa region and a concomitant reduction in elution of free 125I-IGF-1. Protein restriction markedly depressed IGF-1 binding at ～150 kDa in the plasma of diluent and non-immune Ig treated groups. Anti-IGF-1 Ig treatment was effective in preventing this decrease in ～150 kDa binding. Thus, anti-IGF-1 Ig appears to have a beneficial effect on dietary intake in protein-restricted rats, which is associated with induced changes in IGF-1 binding profiles in plasma.     

The effect of inhibition of prostaglandin synthesis on ovarian hypertrophy in the rat.

Aspirin and indomethacin, inhibitors of prostaglandin biosynthesis, were utilized to determine the role of prostaglandins (PGs) in ovarian weight gain in rats following unilateral ovariectomy or treatment with PMSG. After unilateral ovariectomy, the compensatory ovarian hypertrophy was 185-0% compared with 139-8% and 97-5% in rats treated with indomethacin and aspirin, respectively. The adrenal weights in rats treated with aspirin were also reduced significantly. Administration of PGE2 or PGF2alpha with aspirin reversed the effect of aspirin on the adrenals but had no effect on the ovarian weight. Indomethacin and aspirin treatment of animals injected with PMSG also reduced the ovarian weight gain. If 100 mug PGE2 were given twice daily, this effect was reversed in both groups but thrice daily administration had no effect on rats receiving aspirin. In PMSG-treated rats, 100 mug PGF2alpha twice daily did not reverse the effect of indomethacin and aspirin, and actually enhanced the effect of aspirin.     

Topiramate Reduces Energy and Fat Gains in Lean (Fa/?) and Obese (fa/fa) Zucker Rats

Objective: This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats. Research Methods and Procedures: A 2 × 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg). Results: The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals. Discussion: The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.     

S 23521 Decreases Food Intake and Body Weight Gain in Diet‐Induced Obese Rats

Objective: To investigate the effect of S 23521, a new glucagon‐like peptide‐1‐(7‐36) amide analogue, on food intake and body weight gain in obese rats, as well as on gene expression of several proteins involved in energy homeostasis. Research Methods and Procedures: Lean and diet‐induced obese rats were treated with either S 23521 or vehicle. S 23521 was given either intraperitoneally (10 or 100 μg/kg) or subcutaneously (100 μg/kg) for 14 and 20 days, respectively. Because the low‐dose treatment did not affect food intake and body weight, the subcutaneous treatment at high dose was selected to test the effect on selected end‐points. Results: Treated obese rats significantly decreased their cumulative energy intake in relation to vehicle‐treated counterparts (3401 ± 65 vs. 3898 ± 72 kcal/kg per 20 days; p < 0.05). Moreover, their body weight gain was reduced by 110%, adiposity was reduced by 20%, and plasma triglyceride levels were reduced by 38%. The treatment also improved glucose tolerance and insulin sensitivity of obese rats. Regarding gene expression, no changes in uncoupling protein‐1, uncoupling protein‐3, leptin, resistin, and peroxisome proliferator‐activated receptor (PPAR)‐γ were observed. Discussion: S 23521 is an effective glucagon‐like peptide‐1‐(7‐36) amide analogue, which induced a decrease in energy intake, body weight, and adiposity in a rat model of diet‐induced obesity. In addition, the treatment also improved glucose tolerance and insulin sensitivity of obese rats. These results strongly support S 23521 as a putative molecule for the treatment of obesity.     

Effects of glucagon on physiologic and compensatory renal growth in the rat

Glucagon has been implicated as a growth-promoting hormone in the kidneys of diabetic animals, but its role in the nondiabetic state is unknown. We evaluated the effect of subcutaneous glucagon administration on renal growth in intact rats with two kidneys and after 50% reduction in renal mass. The relative kidney weight was increased in intact rats treated with a glucagon infusion for 7 days (p less than 0.01), but decreased in uninephrectomized rats treated with glucagon (p less than 0.05). Absolute kidney weight gain and rates of renal DNA synthesis were also significantly blunted by glucagon infusion in uninephrectomized rats. These data suggest that 'physiologic' and 'compensatory' renal growth are governed by separate processes. Furthermore, the observation that glucagon promotes renal growth in intact nondiabetic animals supports its possible role as a growth factor in the early stages of diabetes.     

The Role of Thermogenesis in Antipsychotic Drug‐induced Weight Gain

The administration of antipsychotic drugs to human patients or experimental animals leads to significant weight gain, which is widely presumed to be driven by hyperphagia; however, the contribution from energy expenditure remains unclear. These studies aim to examine the contribution of shifts in energy expenditure, particularly those involving centrally mediated changes in thermogenesis, to the body weight gain associated with the administration of olanzapine to female Sprague Dawley rats. Olanzapine (6 mg/kg/day orally) caused a transient increase in food intake but a maintained increase in body weight. When pair‐fed rats were treated with olanzapine, body weight continued to rise compared to vehicle‐treated rats, consistent with a reduction in energy expenditure. Brown adipose tissue (BAT) temperature, measured using biotelemetry devices, decreased immediately after the onset of olanzapine treatment and remained depressed, as did physical activity. UCP1 expression in interscapular BAT was reduced following chronic olanzapine treatment. An acute injection of olanzapine was preceded by an injection of a retrograde tracer into the spinal cord to evaluate the nature of the olanzapine‐activated neural pathway. Levels of Fos protein in a number of spinally projecting neurons within discrete hypothalamic and brainstem sites were elevated in olanzapine‐treated rats. Some of these neurons in the perifornical region of the lateral hypothalamus (LHA) were also Orexin A positive. These data collectively show a significant impact of thermogenesis (and physical activity) on the weight gain associated with olanzapine treatment. The anatomical studies provide an insight into the central neuroanatomical substrate that may subserve the altered thermogenic responses brought about by olanzapine.     

Antiobesity effects of a novel lipid synthesis inhibitor (Ro 22-0654)

The present studies were conducted to determine the antiobesity effects of a novel inhibitor of hepatic fatty acid synthesis, 4-amino-5-ethyl-3-thiophene-carboxylic acid methyl ester hydrochloride (Ro 22-0654/001). Weight gain was decreased by treatment with Ro 22-0654 in Sprague Dawley and in lean or obese Zucker rats. Food intake was only transiently suppressed during the first few days of each study. The decreased weight gain in treated rats could be accounted for almost entirely by a decrease in total body lipid levels. Hepatic fatty acid synthesis was inhibited following two months of treatment, in rats fed either a 1% or 10% corn oil diet. It is suggested that the inhibition of hepatic fatty acid synthesis may account, in part, for the reduced weight gain.     

The effect of thyroid hormone on mitochondrial biogenesis and cellular hyperplasia

The purpose of this investigation was to study the effects of thyroid hormone treatment on the levels of DNA, RNA, and protein in hepatocytes and hepatocyte mitochondria. A preliminary investigation was conducted to establish an effective dosage of thyroid hormone. Male Sprague-Dawley rats were given daily subcutaneous injections ofl-thyroxine (20, 40, or 60 µg/100 g body weight) and the following determinations made over a 14-day period: (1) body weight; (2) total body respiration; and (3) the activities of the mitochondrial enzymes, succinate dehydrogenase and -glycerophosphate dehydrogenase. Dosages of 20 and 40 µgl-thyroxine/100 g body weight produced significant stimulation of (a) total body respiration and (b) succinate dehydrogenase and -glycerophosphate dehydrogenase activities without any inhibitory effects on normal weight gain of the animals. Injections of 40 µgl-thyroxine/100 g body weight were utilized for subsequent studies. Hepatic DNA levels of treated animals were greater than age-paired control values by 28% on day 7 and 43% by day 14. Total liver RNA levels of thyroid-treated animals were 17% greater than those of controls by day 7 and 47% greater by day 14. Analyses were also performed on mitochondria quantitatively collected by rate zonal centrifugation. Total liver mitochondrial DNA levels in thyroid-treated animals were greater than age-paired controls by 79% at 7 days but only 67% at 14 days since a small gain occurred in control animals and no further increase occurred in treated rats during the second week. Mitochondrial RNA and protein from treated livers were 26% and 16% higher, respectively, than age-paired controls at day 7 and 40% and 58% higher, respectively, at day 14. The results of this study indicated that thyroid hormone treatment produces hyperplasia and an increase in mitochondrial number and mass in rat liver.     

Further studies on the effects of dehydroepiandrosterone on hepatic metabolism in BHE rats

Two experiments were conducted to determine the effects of dehydroepiandrosterone (DHEA) on de novo fatty acid synthesis and oxygen consumption in BHE rats fed a 65% glucose diet. In Experiment 1, starved glucose-refed rats were injected ip with 120 mg of DHEA/kg body wt and hepatic de novo fatty acid synthesis was measured. DHEA-treated rats synthesized less fatty acid in response to starvation refeeding than nontreated rats. In Experiment 2, weanling rats were fed the glucose diet for 4 weeks. One-hundred twenty milligrams of DHEA/kg were injected daily for 3 weeks. Body weight gain, epididymal fat pad weight, and carcass lipid were less in the DHEA-treated rats than in the control rats. Mitochondrial respiration was less and liver size was greater in DHEA-treated rats compared with control rats. Whole body oxygen consumption was increased in DHEA-treated rats, suggesting that this steroid might be stimulating futile energy cycles involving lipid and protein turnover possibly through its effect on glucocorticoid and thyroid hormone function.     

Anabolic actions of a mixed beta-adrenergic agonist on nitrogen retention and protein turnover.

Subcutaneous administration of a mixed beta-agonist induced increases in muscle (+13%) and heart (+17%) weights, which were accompanied by a reduction in back (-13%) and perirenal (-27%) fat stores in young male rats, while no changes in liver were observed. The values of nitrogen retention (mg/day) were significantly higher in the beta-agonist treated animals (+16%) as well as those of muscle DNA content (+8%). On the other hand, no statistically significant changes in muscle protein synthetic activity (g protein synthetized/g RNA) were detected (control: 13.4 vs treated: 14.6), while muscle proteolytic activity was decreased (-9%) in those rats administered with the repartitioning agent. In this context, it is suggested that the anabolic effect of metaproterenol should be attributed to a reduction in muscle protein degradation rather than to changes in protein synthesis.     

Effect of a selectiveβ 2-adrenergic agonist (Cenbuterol) on energy balance and body composition in normal and protein deficient rats

In rats fed a normal (22% protein) diet, injection of clenbuterol (1 mg/kg/d for 21 d) did not affect energy intake, energy expenditure or weight gain, but reduced energetic efficiency, and fat and energy gains and increased body protein content. Presenting a low-protein (8%) diet reduced energy intake, gain and efficiency, body protein content and the mass of the gastrocnemius muscle when compared to rats fed the control diet. Injection of the protein-deficient rats with clenbuterol (1 mg/kg/d for 21 d) caused hypophagia and reduced body weight and energy gains, energy expenditure and total body fat. However, the total body content of protein was not significantly reduced and the percentage of body protein in this protein deficient, clenbuterol-treated group was greater than that of untreated rats on both the high- and low-protein diets. The ratio of body protein to fat following clenbuterol treatment was increased by over 50% in both normal and protein-deficient rats. The results show that in protein deficient animals, clenbuterol treatment may help conserve body protein at the expense of fat, resulting in a smaller, but leaner body mass.     

Biosafety evaluation of two Beauveria bassiana products on female albino rats using acute oral test

Application of bio-pesticides in agriculture has been developed as alternative agents to conventional pesticides due to residues accumulating which causing detrimental effects to human and environment. The aim of this investigation is to evaluate biosafety of a bio-insecticide Beauveria bassiana using two products in female rats by single oral dose through hepato- and renal toxicity, hematotoxicity and lipid profile. The two products from B. bassiana (AUMC 9896) were metabolic crude (MC), and wettable powder formulation (WP) of the local isolate. Results showed a significant increase in values of erythrocytes (RBCs), leucocytes (WBCs), platelet count (Plt) and the absolute differential WBC counts. Liver enzymes (AST, ALT, and ALP) and globulin (Glb) content were reduced in the exposed female rats with both types of B. bassiana in comparison to controls. While ratio of AST/ALT and A/G, total protein level (TP) and albumin (Alb) were raised in Beauveria bassiana -treated rats (Bb - treated rats). Urea and creatinine concentrations decreased or increased significantly in treated rats. Moreover, there was a decline in the serum of lipid profiles in WP - treated rats, but LDL levels increased in all treated animal. Additionally, no mortality or toxicity in all treated. All animals treated showed non-significant modifications in body weight gain and a slight change in relative liver weights when compared to controls. These results suggest that both treatments effect markedly on function and somatic index of the liver and slight effects on CBC and lipid profile aspects of treated female rats.     

Effects of captopril on the development of rat doxorubicin nephropathy.

The effects of a daily administration of an anti-converting enzyme inhibitor. Captopril (CPT) (100 mg/kg/orally), on the development of functional and morphological alterations induced in rats by a single injection (7.5 mg/kg/iv) of Doxorubicin (DXR) (Adriamycin*), were investigated. Twenty-four-hour protein excretion, urine output, food intake, water intake, and body weight gain were measured weekly for 30 days. Transmission and scanning electron microscopy observations were performed on kidney samples after 30 days. Four groups were studied. Group 1 were control rats. Group 2 were rats injected with DXR. Group 3 were rats injected with DXR and treated with CPT for 30 days. Group 4 were rats injected with DXR and treated with CPT for 15 days (CPT treatment started 15 days after DXR injection). Group 1 did not show significant functional or morphological changes. Group 2 showed severe proteinuria, significant increase in urinary volume within 2 weeks, significant body weight reduction and diffuse morphological changes. These changes mainly consisted of podocyte swelling, severe foot process fusion, and presence of casts within tubular lumen. Group 3, with respect to group 2, showed a significant reduction of the 24 h protein excretion and urine output. This group displayed morphological changes similar to those observed in group 2, but with a focal distribution. Group 4 showed functional and morphological changes comparable with those of group 2. It is concluded that CPT partially inhibits the development of the functional and morphological damage induced by DXR in the rat kidney. However, CPT did not influence the natural development of nephropathy when treatment started 15 days after DXR injection.     

Performance of the African giant rat (Cricetomys gambianus Waterhouse) on commercial rations and varying dietary protein levels

The growth performance of 24 weanling giant rats was studied in 2 experiments of 30 weeks duration with commercial livestock rations and graded levels of protein. Daily average liveweight gain was 5.1-7.3 g, food consumption 26.9-36.3 g on 6 diets. Food intake, growth rate and food efficiency ratio were very similar using the different commercial diets. Growth performance improved as the dietary protein level was raised from 10 to 13%, but a further increase to 16% did not result in greater growth. The commercial pig ration and the experimental diet containing 13% dietary protein level were found to give satisfactory growth, and are recommended for studies with these animals.     

Effect of corticosterone treatment on muscle protein turnover in adrenalectomized rats and diabetic rats maintained on insulin

The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [(14)C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.     

Changes in protein turnover in hypertrophying plantaris muscles of rats: effect of fenbufen--an inhibitor of prostaglandin synthesis

Plantaris muscle of the right hind limb of rats was subjected to hypertrophic stimulus by section of the tendons of the right gastrocnemius muscle. The RNA and protein content and the fractional rate of protein synthesis were elevated both 3 and 7 days after operation compared both with the unoperated left limb and with sham-operated control rats. The rate of protein degradation, calculated from the difference between the fractional rates of protein synthesis and protein gain of the muscles, was elevated in the plantaris 3-7 days after tenotomy. Dietary administration of the drug fenbufen reduced the RNA content and the ratio of RNA:protein in muscles from control animals. In one group of tenotomised rats administration of fenbufen commenced 3 days before tenotomy and resulted in a reduction in the ratio RNA:protein of the muscles of the left limb 3 days after the operation. Four days later, i.e. 7 days after tenotomy, both the ratio RNA:protein and the fractional rate of protein synthesis were significantly reduced in the fenbufen treated rats. In spite of these effects, fenbufen did not impair the ability of the plantaris to hypertrophy since the drug also reduced the rate of protein degradation.