Effect of high phosphorus diet on phosphorus metabolism in parathyroidectomized rats

To determine the parathyroid hormone (PTH) action on kidney and bone by high phosphorus (P) diet, this study investigated PTH/PTH-related peptide (PTHrP) receptor mRNA expression in 6-week-old parathyroidectomized (PTX) rats received constant amount of PTH. To maintain serum PTH levels equally to sham operated rats, PTX rats were constantly exposed to rPTH (1-34) and fed a control diet (0.3% P) and a high P diet (1.2% P) for 7 days, respectively. There were no significant differences in serum PTH (1-34) concentration in rats fed the control diet. In sham groups, serum PTH concentrations, both (1-84) and (1-34) fragments, were increased in rats fed the high P diet than in rats fed the control diet. Urinary excretions of P and C-terminal telopeptides of type I collagen were significantly increased in both PTX and sham rats by the high P diet. PTH/PTHrP receptor mRNA expression in kidney and femur was not changed in both PTX and sham rats by the high P diet. In conclusion, high P diet did not change PTH action in PTX rats and increased urinary excretion of P and bone resorption regardless of PTH action.     

High phosphorus feeding decreases the expression of renal PTH/PTHRP-receptor mRNA in rats

Dietary intake of high phosphorus (P) is well-described to increase serum levels of PTH, however, how this increased serum PTH affects the PTH actions in major target tissues, particularly in kidney, remains uncovered. We therefore undertook to clarify this point in intact animals fed the high-P diet by examining various parameters of the PTH actions. Twelve weanling Wistar male rats were assigned randomly into the groups; a control group Ca: P = 1: 1 and a high-P group (Ca: P = 1: 3) fed the standard AIN 76 diet supplemented with P (0.5 and 1.5 g/100 g diet). After 3 week feeding, in the high-P diet group, we observed that serum Ca is lowered without difference in serum P when compared to those in the control group. Excretion of urine cAMP, an index of the renal PTH action, was also decreased with higher excretion of urine P by feeding the high P diet. In agreement with the decreased cAMP excretion, a clear reduction in the PTH/PTHrP receptor gene expression estimated by Northern blotting was observed in the kidney irrespective of increased levels of serum PTH. Thus, the present study indicated that high P dietary intake rather reduces the PTH actions in kidney though the serum PTH is increased.     

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO₃) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO₃ groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO₃ 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.     

Restricted diet modifies carbohydrate metabolism in immature rats

The aim of the present work was to study the effect of a restricted diet on carbohydrate metabolism in submandibular glands of female prepuber rats and the influence of arachidonic acid derivatives. Rats of 21 days of age were divided into three groups. Group I: normally fed rats. Group II: restricted diet (50% of the normal food intake). Group III: normally restricted diet with re-feeding. The baseline concentration of tissue glycogen was significantly higher in Group II than in I or III and after 60 min of incubation in a glucose free medium all groups showed a glycogen drop. In addition, the glucose metabolism was increased in Group II. Cycloxigenase inhibitors failed to alter (14)CO(2) levels in Groups I and III. In Group II, indomethacin and acetylsalicylic acid inhibited glucose metabolism, which was reverted by PGE(2) addition. The exogenous arachidonic acid metabolism and different eicosanoids showed that restricted diet significantly increased the production of PGE(2) but diminished PGF(2)(alpha) production. Our results suggest that a restricted diet would lead to a new dynamic equilibrium of glucose homeostasis. Prostaglandins E(2) and F(2)(alpha) would participate by adapting the source of energy to tissue demands while maintaining the metabolic features that characterize puberty.     

Low-protein diet changes thyroid function in lactating rats

Lactating rats were fed with free access to an 8% protein-restricted diet (PR); the control group was fed a 23% protein diet (C). An energy-restricted (pair-fed) group was given the same food as the animals in the control group, but the amounts of food consumed by both PF and PR were about the same. The body weight and serum albumin concentration of PR and PF dams were significantly (P < 0. 05) lower than that of the controls. The PR group had a significant increase in serum-free triiodothyronine (FT3) concentration, 24-hr mammary gland and milk radioiodine (I131) uptake (67%, 278%, and 200%, respectively) as compared with the controls. On the other hand, those animals had a significantly lower serum-free thyroxine (FT4) concentration and 2- and 24-hr thyroid I131 uptake (67%, 64%, and 74%, respectively). Protein malnutrition during lactation did not alter thyroid or liver 5'-deiodinase activity significantly. However, PF dams had a significantly lower (25%) thyroid 5'-deiodinase activity. These data suggest that protein-restricted lactating dams had an adaptive change in the thyroid function, which could be important to increase the transference of iodine or triiodothyronine through the milk to their pups and prevent sequelae of neonatal hypothyroidism.     

High molecular weight poly-gamma-glutamic acid regulates lipid metabolism in rats fed a high-fat diet and humans

We investigated the effect of high molecular weight polygamma- glutamic acid (hm gamma-PGA) on adiposity and lipid metabolism of rats in the presence of an obesity-inducing diet. Thirty-two Sprague-Dawley rats were fed either a normal-fat (11.4% kcal fat, NFC) or high-fat (51% kcal fat, HFC) diet. After 5 weeks, half of each diet-fed group was treated with hm gamma-PGA (NFP or HFP) for 4 weeks. The HFC group had significantly higher body weight, visceral fat mass, fasting serum levels of total cholesterol, LDL cholesterol, and leptin, and lower serum HDL cholesterol level compared with those of the NFC group (p < 0.05). Treatment with hm gamma-PGA decreased body weight gain and perirenal fat mass (p<0.05), fasting serum total cholesterol, and mRNA expression of glucose-6- phosphate dehydrogenase (G6PD), regardless of dietary fat contents (p < 0.01). However, hm gamma-PGA increased serum HDL cholesterol in the HFC group (p < 0.05). In vitro, 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCoA) reductase activity was suppressed by the addition of hm gamma-PGA. In agreement with observations in animal study, the supplementation of hm gamma-PGA (150 mg/day) to 20 female subjects in an 8-week double-blind, placebocontrolled study resulted in a tendency to decrease total cholesterol and LDL cholesterol concentrations. We thus conclude that dietary supplementation of hm gamma-PGA may act as a hypocholestrolemic agent, secondary to its inhibitor effect on HMG-CoA reductase, and decrease abdominal adiposity by decreasing hepatic lipogenesis. The present study is an important first step in establishing the effect of hm gamma-PGA on cholesterol levels in rats and humans.     

Copper metabolism in analbuminaemic rats fed a high-copper diet

Copper metabolism in male Nagase analbuminaemic (NA) rats was compared with that in male Sprague Dawley (SD) rats fed purified diets containing either 5 or 100 mg Cu/kg diet. Dietary copper loading increased hepatic and kidney copper concentrations in both strains to the same extent, but baseline values were higher in the NA rats. There was no strain difference in true and apparent copper absorption nor in faecal endogenous and urinary copper excretion. NA rats had higher levels of radioactivity in kidneys at 2 hr after intraperitoneal administration of ⁶⁴Cu. As based on the distribution of added ⁶⁴Cu, about 70% of plasma copper appeared to be in the non-protein compartment in the NA rats, whereas in SD rats, it was only about 1%. It is concluded that the NA rats are able to maintain a relatively normal metabolism of copper, even after dietary copper challenge. In the NA rats, zinc concentrations in kidneys, liver and urinary zinc excretion were elevated when compared with SD rats. The high-copper diet did not affect tissue zinc concentrations and apparent zinc absorption in both strains of rats.     

High protein diet in pregnancy. Effects on neonatal metabolism

The effect of a high protein diet (20% casein + D,L-methionine) administered to Wistar rats during pregnancy on some aspects of cellular growth and RNA metabolism of progeny has been studied. Comparisons were made with well-nourished (10% casein + D,L-methionine) controls. Newborns individual weight, litter weight and number of newborns per litter were unmodified. However, neonate protein content dropped significantly when compared with controls. Both rate of DNA and number of nuclei were unchanged. Protein/DNA ratio (cellular size relative to protein) decreased, which might have led to an atrophy phenomenon, even if the newborn weight/number of nuclei ratio was not modified. Acid DNase activity rose, bringing about DNA breakdown. Total RNA content together with RNase activity fell in newborn from rats suffering high protein diet. Moreover, protein synthesis capacity (RNA/protein ratio) did not change. These results suggest that the administration of a high protein diet to pregnant rats lead to changes in newborn protein rate and nucleic acid turnover by modulating specific nuclease activity.     

Iron and copper metabolism in analbuminaemic rats fed a high-iron diet

The metabolism of iron and copper in male Nagase analbuminaemic (NA) and Sprague Dawley (SD) rats was compared. Relative liver weight was higher and spleen weight significantly lower in NA than SD rats. In NA rats, red blood cell count, haemoglobin and haematocrit were lower, whereas plasma transferrin, total iron-binding capacity and mean corpuscular haemoglobin were higher when compared with SD rats. Iron concentrations in plasma, liver, kidneys and heart were higher, and those in the spleen and tibia were lower, in NA rats. The iron concentrations in liver and spleen were positively correlated with the amount of brown pigment as observed histopathologically. Bile flow as well as biliary iron and copper excretion were higher in NA than SD rats. Copper concentrations in liver, kidneys and plasma were higher in NA rats. Plasma levels of ceruloplasmin were about two-fold higher in NA rats. The feeding of a high-iron diet reduced kidney copper concentrations in both strains of rats, which was associated with a decrease in the absorption and biliary excretion of copper.     

Postprandial metabolism and aversive response in rats fed a threonine-devoid diet

Lack of an indispensable amino acid in the diet induces a rapid reduction in food intake. In this study, we assessed whether the anorectic signal after ingestion of a meal lacking threonine originated from either direct perception of the decrease in plasma threonine or from an indirect effect related to increased postprandial amino acid catabolism and energy expenditure. We observed that 3 g of such a meal was sufficient to induce an aversive response to the diet within 2 h. Postprandial changes to plasma ammonia and urea, urinary urea, and energy metabolism did not differ from those measured after a control meal. In contrast, plasma threonine levels fell within 1 h after the meal. It is concluded that an increase in postprandial energy expenditure is not involved in the anorectic response to eating a threonine-devoid diet. The drop in plasma threonine levels may be a potential signal, but the fact that the decrease in food intake occurred 1 h after the decrease in plasma threonine questions a direct causal relationship.     

Hypocholesterolaemic action of Lactobacillus plantarum VJC38 in rats fed a cholesterol-enriched diet

This study was conducted to evaluate hypocholesterolaemic activity of probiotic strains Lactobacillus plantarum VJC38 and VJI21 in Wistar albino rats fed a cholesterol-enriched diet. The experimental animals were divided into five groups (n = 6) viz., normal diet control group (NDC), hypercholesterolaemic diet (HD) control group (HDC), HD supplemented with 3 × 108 CFU/ml of L. plantarum VJC38 group (HD-C38), HD supplemented with 3 × 108 CFU/ml of L. plantarum VJI21 group (HD-I21), and HD supplemented with 3 × 108 CFU/ml of L. rhamnosus GG group (HD-GG) as positive control. Animals were administered bacterial culture by oral gavage once daily for 45 days. After trial, animals were sacrificed and blood samples were collected. Serum total cholesterol (T-CHO), triglyceride (TG), high-density lipoprotein (HDL) cholesterol, glucose, glutamyl pyruvate transaminase (GPT), and glutamyl oxaloacetate transaminase (GOT) levels were determined. Serum low-density lipoprotein (LDL) cholesterol levels were estimated using the Friedewald’s equation. Liver and fecal lipid contents and fecal cholic acids were measured. Serum T-CHO levels were significantly decreased by 15.6 and 17.4% in the HD-GG and HD-C38 groups, respectively, but not in the HD-I21 group compared with HDC group (P < 0.05). HD-GG and HD-C38 groups showed 26.3 and 27.2% reduction in serum LDL cholesterol, respectively when compared with HDC group (P < 0.05). Serum LDL cholesterol levels in HD-I21 group were not significantly different from HDC group. Serum TG levels in the HD-GG and HD-C38 were decreased by 14.2 and 22.8%, respectively compared with HDC group (P < 0.05). Liver T-CHO and TG levels in the HD-GG, HD-C38, and HD-I21 were reduced significantly compared with the HDC group (P < 0.05). Atherogenic coefficient values of HD-GG, HD-C38, and HD-21 were significantly decreased compared with HDC group (P < 0.05). Serum GPT levels in the HD-GG, HD-C38, and HD-I21 were decreased by 20.6, 10.9, and 20.6%, respectively, vs. the HDC group. Serum GOT levels were not significantly different among the groups. Serum glucose levels were significantly low in HD-GG, HD-C38, and HD-I21 compared with HDC group (P < 0.05). Fecal cholesterol and cholic acid levels were significantly higher in the HD-C38 and HD-GG groups than other groups (P < 0.05). This study suggests that L. plantarum VJC38 exhibits hypocholesterolaemic effect through hydrolysis of conjugated bile acids in the small intestine and excretion of cholesterol in feces. Lactobacillus plantarum VJC38 could be used as a potential cholesterol-lowering probiotic after validation of the hypocholesterolaemic activity in placebo-controlled human clinical trials.     

Asbestos-stimulated changes in nitric oxide and iron metabolism in rats

Under intratracheal asbestos fibers installation it has been investigated NO synthesis in the lung and liver tissues of Wistar rats by EPR method. Asbestos A6-45, sifted through the sieve with size 0.1 mm, has been administrated in a dose of 5 mg/kg. To evaluate the NO synthesis EPR and NO-trap methods have been used. The amplitude of EPR signal "trap-NO" in the lung samples was 12, 16 and 14 times greater than in controls on the 3th, 6th and 10th days after asbestos installation and was corresponding to NO rate of about 2 mkmol/(g x h). In the liver samples of asbestos-stimulated animals the NO level contained in the non-heme iron nitrosyl complexes was about 2 mkmol/g. Thus, the asbestos fibers stimulate NO synthesis not only in the lung tissue, but also in other organs. The obtained data shows that under NO hyperproduction certain changes in iron metabolism take place, such as: the decrease of transferrin iron and the accumulation of ferric iron not bound with transferrin. The accumulation of ferric iron not shielded by proteins is one of the oxidative stress triggers.     

Morphofunctional changes in gastrointestinal tract of rats due to cafeteria diet.

Female rats fed a cafeteria diet from birth developed obesity at 60 days of age and their stomach, small intestine and caecum were enlarged when compared with controls, i.e. these regions had greater food storage capacity. In spite of the enlargement, these regions had similar or reduced weight and linear density, which is seen as proof of reduced mechanical performances. Cafeteria diet produced increased glucose duodenal absorption in older animals unlike the typical reduction known in controls. Tryptophan absorption was maintained high in adulthood, compensating for the low structural nutritive properties of the cafeteria diet. The results are interpreted as an adaptation to the cafeteria diet effects and properties: the characteristic overeating of foodstuffs with greater energy density, lower mechanical requirements and lower structural nutritive value than pelleted chow.