The effect of dietary copper and zinc on cholesterol metabolism

The effects of different amounts of dietary zinc and copper on cholesterol metabolism in the rat were investigated. The levels of the minerals used were comparable to those likely to occur in a normal mixed North American diet. Although the different levels affected the serum, liver, and femur concentrations of the minerals, they had no effect on the levels of serum and liver, total, esterified or free cholesterol, or on high density lipoprotein cholesterol. It was concluded that dietary copper and zinc, at levels likely to occur in a normal mixed diet, are not significant factors in cholesterol metabolism.     

Effects of dietary corn and olive oil versus coconut fat on biliary cholesterol secretion in rats

We have studied the effects of dietary corn and olive oil versus coconut fat on bile formation and fluidity of hepatic plasma membranes in rats. After 4 weeks of feeding the purified diets containing 9% (w/w) of the test fats, there was no difference in plasma cholesterol concentration between the dietary groups. The amount of free and esterified cholesterol in the liver was significantly higher in rats fed either corn oil or olive oil as compared with coconut fat. In the rats fed olive oil, but not in those fed corn oil this was associated with lower rates of biliary phospholipid excretion. Bile flow was not differently influenced by the three dietary fats. Hepatic plasma membranes of the rats fed corn or olive oil contained more cholesterol and less phospholipids than those on coconut fat, which was, however, not accompanied by changes in fluidity of the membranes. These results indicate that in rats the type of dietary fat can induce considerable changes in hepatic cholesterol metabolism without affecting plasma cholesterol concentrations, and without consistent effects on biliary cholesterol secretion.     

Effect of dietary lactose at levels comparable to human consumption on cholesterol and bile acid metabolism of conventional and germfree rats

In recent years, the use of milk products and the concomitant intake of lactose have been tentatively linked to the etiology of cardiovascular disease. An effect of lactose on the microbial modification of acid and neutral sterols has been suggested. In the present study lactose intake, ranging up to 30% of total diet increased beta-muricholic (beta-MC) but not cholic acid concentrations in conventional (CV) rat small intestine to the extent that at the 20% and 30% intake level, the intestinal cholic: beta-MC ratio approached that in germ-free (GF) rats. Total intestinal bile acid (BA) content increased by approximately 1/3, but remained at less than half the value found in GF rats. At lactose intake levels within a range corresponding to the consumption of dairy products often recommended for adult man (5% to 10%) only moderate changes in intestinal, and little change in fecal BA were found during and after the 3 months experimental period. Intestinal beta-MC was increased in the presence and in the absence of an intestinal microflora. Experiments with GF rats fed 10% lactose or 10% maltose indicated that this increase is evoked similarly by both carbohydrates. The slight increase in serum cholesterol levels seen with disaccharide feeding, which became evident only in the GF rats, was again not specific for lactose. No influence was found of lactose feeding on liver cholesterol values. Comparison of CV rats fed nonsterile and radiation-sterilized lactose-containing diets suggested that this mode of sterilization has only a minor influence on the resulting data. When GF experiments are to be incorporated, sterilazation of diet by irradiation with 3.5 to 4.0 X 10(6) Rad is preferable to autoclaving. The present data indicate that no major effect specifically related to a normal dietary intake of lactose on cholesterol and BA metabolism of the adult rat could be demonstrated for the duration of these experiments.     

Effects of diabetes mellitus on cholesterol metabolism in man

In view of the reported excess prevalence of atherosclerosis and cholelithiasis in diabetes, we investigated several aspects of cholesterol metabolism under metabolic ward conditions in six Pima Indians with maturity-onset diabetes mellitus. Cholesterol balance (13.5 versus 11.0 mg per kilogram per day, P less than 0.05), fecal bile acid excretion (415 versus 261 mg per day, P less than 0.05), bile acid pool size (3150 versus 1950 mg, P less than 0.05), fasting plasma cholesterol (193 versus 160 mg per deciliter, P less than 0.05) and plasma triglycerides (251 versus 150 mg per deciliter, P less than 0.05) were higher during uncontrolled hyperglycemia than during relative euglycemia on insulin. The increased plasma lipid levels and total cholesterol synthesis during hyperglycemia may contribute to the acceleration of atherosclerosis in diabetes mellitus. Gallbladder bile was significantly more saturated with cholesterol (181 per cent versus 114 per cent, P less than 0.05) during insulin treatment than during uncontrolled hyperglycemia. Bile lipid composition was thus more favorable to cholesterol precipitation and gallstone formation during insulin treatment than in the untreated diabetic state.     

Metallothionein and its relationship to the metabolism of dietary zinc in rats

Metallothionein (MTN), a low molecular weight cytoplasmic metalloprotein has previously been implicated in the metabolism of Zn. Experiments were conducted with rats to determine the effect of feeding varying levels of dietary Zn for short periods on the increase or decrease in MTN-bound Zn. The results indicated that MTN-Zn in both liver and intestinal mucosal cytosol responded rapidly to an altered dietary Zn level and that serum Zn was directly related to the appearance of MTN. 65Zn absorption also responded rapidly to a change in dietary Zn and was inversely correlated with intestinal mucosal MTN-Zn. Hepatic 65Zn uptake appeared to be directly correlated with liver MTN-Zn. A 24 hour fast increased MTN-Zn in rats fed two different levels of Zn except in those rats that were previously treated with actinomycin D. The antibiotic, which blocks DNA-dependent RNA synthesis, appeared to block Zn uptake from blood to the liver. These findings offer support for the involvement of MTN in zinc metabolism.     

Effect of dietary fats and sesamin on the lipid metabolism and immune function of Sprague-Dawley rats

We examined the effect of three dietary fats, safflower oil (SAF) rich in linoleic acid, borage oil (BOR) rich in gamma-linolenic acid, and perilla oil (PER) rich in alpha-linolenic acid, on the lipid metabolism, and chemical mediator and immunoglobulin levels in Sprague-Dawley rats, as well as the dietary effect of sesame-derived antioxidative sesamin. The serum cholesterol, phospholipid, triglyceride, prostaglandin E2 level and splenic leukotriene B4 level were lower in the rats fed on BOR or PER than in those fed on SAF. SES feeding suppressed the expression of the lipid-decreasing effect of BOR, but not in the rats fed on PER. In respect of the fatty acid composition of the liver and spleen, PER feeding gave a lower arachidonic acid level, and higher eicosapentaenoic and docosahexaenoic acid levels than SAF feeding did, while the effect of BOR feeding was marginal. The effect of SES feeding on fatty acid composition was much smaller than that of dietary fats. In respect of immunoglobulin production, PER + SES feeding gave the lowest IgE productivity in the mesenteric lymph node lymphocytes. These results suggest that PER feeding regulated lipid metabolism and exerted an anti-allergic effect by a different mechanism from that with BOR feeding.     

Effects of dietary molybdenum on the metabolism of copper and molybdenum in young cattle

On separate occasions young cattle were injected intrarumenally with 99Mo or 64Cu or intravenously with 64Cu. The metabolism of the isotopes were compared to evaluate metabolic changes associated with molybdenum-induced copper deficiency. Molybdenum-99 metabolism was the same in both controls and experimental subjects. Marked differences in plasma kinetics were observed following intrarumenal 64Cu injection, with experimental animals displaying earlier plasma appearance and maintaining higher plasma levels than did controls. Similarly, higher plasma levels, more rapid plasma reappearance and greater fecal excretion were observed following intravenous injection of 64Cu in the experimental animals than in controls. A mechanism involving abnormal ceruloplasmin synthesis associated with the molybdenum-copper interaction is proposed.     

Variations in dietary fat and cholesterol intakes modify antioxidant status of SHR and WKY rats

The effects of varying dietary fat saturation [butter (B), beef tallow (BT)] or polyunsaturation [(n-6) soybean oil (SBO), (n-3) menhaden oil (MO)] and cholesterol content (0.05 and 0.5 g/100 g) on systolic blood pressure (SBP), plasma lipids and tissue antioxidant status were investigated in 14-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Varying dietary fat composition for 9 wk had no influence on SBP in either SHR or WKY rats. Rats fed MO diets exhibited smaller (P < 0.05) body weight gains, lower (P < 0.05) feed efficiency ratios and lower (P < 0.05) plasma cholesterol concentrations than those fed the B, BT and SBO diets. Significant (P < 0.05) interactions for animal strain x cholesterol intake and animal strain x fat source were noted for serum cholesterol concentrations. SHR exhibited higher (P < 0.05) RBC and liver catalase (CAT), and heart and liver superoxide dismutase (SOD) activities similar to those of WKY rats. The lower (P <0.01) RBC, heart and liver glutathione peroxidase (GSH-Px) activities observed in SHR coincided with higher (P <0.01) glutathione reductase (GSSG-Red), compared with WKY rats. Dietary cholesterol intake had no effect on RBC, heart and liver total sulfhydryl concentration or GSH-Px activities, but increased (P <0. 001) liver GSSG-Red. Feeding MO resulted in lower (P <0.001) RBC and heart GSH-Px activities. In contrast, feeding B and BT resulted in lower GSH-Px in liver. The significant (P < 0.01) animal strain x fat source interaction obtained for liver GSH-Px activity indicated that SHR responded differently to polyunsaturated fatty acid feeding than their WKY counterparts. Diet-induced changes in tissue antioxidant status were tissue specific and did not affect the development of hypertension in SHR.     

Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on cholesterol metabolism in rats fed on a fat- and cholesterol-enriched diet

The effect of a mixture of organisms (a probiotic mixture) comprising Bacillus, Lactobacillus, Streptococcus, Clostridium, Saccharomyces and Candida (10(7-8) colony-forming units/g rice bran of each component) on lipid metabolism was compared with that of L. acidophilus and that of S. faecalis. There were four treatment groups: rice bran (control), the mixture of organisms, L. acidophilus or S. faecalis (30 g/kg) were given to rats in a fat- and cholesterol-enriched diet for 4 weeks. The serum total cholesterol concentration of the group fed on the mixture of organisms was reduced by 15-33% compared with the other groups at the end of the 4-week feeding period (P < 0.05). This group also had a lower hepatic cholesterol concentration (36-44%) than the two single-bacteria groups (P < 0.05). 3-Hydroxy-3-methylglutaryl-Co A reductase (NADPH; EC 1.1.1.34) activities of the mixed-organism and L. acidophilus groups were significantly lower (61-63%) than those of the other groups (P < 0.05); the activity of the S. faecalis group was also significantly lower (42%) than that of the control group (P < 0.05). The faecal cholesterol and bile acid concentrations of the mixed-organism group increased compared with those of the L. acidophilus and S. faecalis groups (P < 0.05). The capacity of the mixed-organism cells to bind bile salt in vitro was significantly higher (approximately 50%) than that of the single-bacteria cells (P < 0.05). On the other hand, cholesterol micelle formation for the mixed-organism cells was significantly (approximately 9%) lower than that of the single-bacteria cells (P < 0.05). These results indicate that the mixture of organisms decreased the synthesis of cholesterol in the liver and increased the loss of steroids from the intestine, in rats. Thus, the mixture of organisms had a hypocholesterolaemic role.     

Effects of dietary salt restriction on blood pressure and the renal vasoactive system in the congenitally bilateral hydronephrotic rat

We examined the responses on blood pressure when the renal vasoactive system such as renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) was activated by dietary salt restriction in the congenitally bilateral hydronephrotic rat (BHN). In a low salt diet (LS)-normotensive and normal kidney control rats after 8 weeks from initiating dietary salt restriction, the plasma sodium concentration (PNa) was retained at a level similar to that in the normal diet (ND)-control rats, and plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urinary kallikrein activity (UKA) were about 1.8-, 9.4-and 1.7-fold higher, respectively, than those in the ND-control rats. In addition, LS-control rats had a significantly (p < 0.001) high systolic blood pressure (163 +/- 2.0 mm Hg) compared with that (136 +/- 5.8) of ND-control rats. These results suggest that the activated renal vasoactive system acted for not only sodium retention but also for elevation of blood pressure in LS-control rats. In LS-BHN at week 8, PNa was also retained at a nearly normal level. However, the renal vasoactive system activation for sodium retention was higher than that of LS-control rats; that is, increase of PRA, PAC and UKA were about 3.8-, 24.7-and 10.0-fold, respectively, than in ND-BHN. The higher activation of RAAS, nevertheless, does not affect blood pressure in BHN; that is, both hypertension of BHN fed LS and ND developed similarly. These findings suggest that dietary salt restriction could markedly activate the renal vasoactive system for sodium retention without elevating blood pressure in BHN different from control rats.     

Preventive effect of germinated barley foodstuff on diarrhea induced by water-soluble dietary fiber in rats

The two cases presented illustrate the diagnostic difficulties and recommend an approach to use in patients in whom features of acute renal allograft rejection and posttransplant lymphoproliferative disorder (PTLD) appear simultaneously in allograft biopsies. Both patients developed acute allograft rejection episodes in the early post-transplant period followed by severe immunosuppression (OKT-3) and active Epstein-Barr virus infection. In addition to early recognition of light microscopic features of PTLD, immunohistology and in situ hybridization for EBV complement the diagnostic work-up and provide clues to the prompt diagnosis of rapidly developing PTLD affecting the allograft even in the face of persisting rejection.     

Effect of dietary oils, cholesterol and antioxidant vitamin supplementation on liver microsomal fluidity and xenobiotic-metabolizing enzymes in rats

This study was undertaken to compare the effects of four oils: corn (C), olive (O), hazelnut (H) or fish (F), and the intake of two supplements: cholesterol, 1% (Ch) or dl-alpha-tocopherol acetate, 500 mg/kg, and beta-carotene, 30 mg/kg (V), on liver microsomal fluidity, cyt P450 content and aniline hydroxylase (AH), aminopyrine-N-dimethylase (AND) and UDP-glucuronyltransferase (UDP-GT) activities. Male Sprague-Dawley rats (n = 6/group) were fed semipurified diets containing 15% oil, without or with Ch or V, for 20 days. Dietary intake and feed efficiency were lower in rats fed F. Relative liver weight was higher in animals fed F, similar in O and H, and lower in the group fed C. The intake of V increased feed intake in C+V group and decreased the relative liver weight of F+V group, which also decreased with the intake of F+Ch. Ch intake increased the relative liver weight in all groups consuming vegetable oils. Cyt P450 content was higher in rats fed F. Decreased cyt P450 content was observed in C+Ch and F+Ch groups, while it augmented in H+Ch group. Mixture V increased cyt P450 in rats fed C+V, F+V and O+V. The highest membrane fluidity was observed in rats fed F. Fluidity was also higher in group H versus O or C. The intake of Ch decreased microsomal fluidity in all groups, while V induced an increase in microsomal fluidity in group O+V. Rats fed F exhibited higher enzyme activities. AND activity increased with V only in rats fed H+V, while AH activity increased with V intake in groups F+V and O+V. In the C+V group, fluidity was not affected by V, while the cyt P450 content and UDP-GT activity increased. The O+V group exhibited lower UDP-GT activity and higher fluidity and cyt P450 content. The activity of AH decreased in groups F+Ch and C+Ch. UDP-GT activity was higher in rats fed F. It diminished after the intake of Ch in H+Ch and F+Ch. These results indicate that although AH and AND act in the same microsomal metabolic pathway, their localization into the membrane may be determinant of their activity and the response to dietary lipids. It is shown that F intake exerts the most significant effects upon liver microsomal properties, e.g. higher fluidity, cyt P450 content and enzymatic activities, an effect that prevails over the intake of the supplements tested.     

Effects of phenobarbital on stereoselective metabolism of ifosfamide in rats

Plasma and urinary levels of ifosfamide (IF) enantiomers and their metabolites 2-dechloroethylifosfamide, 3-dechloroethylifosfamide, 4-hydroxyifosfamide, and isophosphoramide mustard were determined for control and phenobarbital-treated male Sprague-Dawley rats by using pseudoracemates and GC/MS and stable-isotope dilution analytical methods. For the control rats, the mean AUC for (S)-IF in plasma was greater than that for (R)-IF (R/S AUC ratio, 0.78) and the mean half-life of 41.8 min for (S)-IF was slightly longer than that of 34.3 min for (R)-IF. Phenobarbital pretreatment significantly decreased the AUC values for (R)-IF and (S)-IF, to 21 and 30% of the control values, respectively, and shortened plasma half-lives for both enantiomers [half-life for (R)-IF, 19.8 min; half-life for (S)-IF, 19.4 min]. The urinary excretion values for (R)-IF and (S)-IF were decreased to 41 and 30% of the control values, respectively. The overall amounts of the metabolites in urine were concomitantly increased. Additionally, there were significant reversals in both the R/S AUC ratio and the urinary excretion of 3-dechloroethylifosfamide. Moreover, the enantioselectivity for the generation of 4-hydroxyifosfamide and isophosphoramide mustard disappeared after phenobarbital treatment. These results strongly suggested that the 4-hydroxylation and dechloroethylation of IF enantiomers were mediated by different P450 isozymes or the same isozyme with different stereochemical selectivities.     

Effects of androgens on dietary self-selection and carcass composition in male rats.

In 3 experiments the aromatizable androgen testosterone propionate (TP, .2 mg/day) increased protein (P) and carbohydrate (C) intake and stimulated body weight gain (BWG) in gonadectomized CD-strain male rats. A higher dose (2.0 mg/day) increased P but not C intake and was less effective in stimulating BWG. Postmortem carcass analyses revealed that the elevated P intake of both TP-treated groups was associated with increased carcass P content. The decreased weight of Ss treated with the high dose of TP was due to a reduction in body fat content. The nonaromatizable androgen 5-α-dihydrotestosterone propionate (DHTP, .2 or 2.0 mg/day) also increased P, (but not C intake) and BWG, but it did not alter carcass composition. Unlike TP, the 2 doses of DHTP were equally effective, but neither dose of DHTP was as effective as the low dose of TP in stimulating P and C intake and BWG. Results suggest that (a) androgens can increase selection of dietary P whether or not they exert significant P anabolic effects; (b) DHTP is not the major metabolite responsible for the increases in P and C intake and in BWG caused by TP; and (c) the decreases in C intake and adiposity in rats treated with the high dose of TP may be mediated by aromatized (estrogenic) metabolites of the androgen. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cardiovascular effects of chronic inhibition of nitric oxide synthesis and dietary salt in spontaneously hypertensive rats

This report presents a study of the effects of the membrane fluidizer, benzyl alcohol, on NHE isoforms 1 and 3. Using transfectants of an NHE-deficient fibroblast, we analyzed each isoform separately. An increase in membrane fluidity resulted in a decrease of approximately 50% in the specific activities of both NHE1 and NHE3. Only Vmax was affected; KNa was unchanged. This effect was specific, as Na+, K+, ATPase activity was slightly stimulated. Inhibition of NHE1 and NHE3 was reversible and de novo protein synthesis was not required to restore NHE activity after washout of fluidizer. Inhibition kinetics of NHE1 by amiloride, 5-(N,N-dimethyl)amiloride (DMA), 5-(N-hexamethyl)amiloride (HMA) and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) were largely unchanged. Half-maximal inhibition of NHE3 was also reached at approximately the same concentrations of amiloride and analogues in control and benzyl alcohol treated, suggesting that the amiloride binding site was unaffected. Inhibition of vesicular transport by incubation at 4 degrees C augmented the benzyl alcohol inhibition of NHE activity, suggesting that the fluidizer effect does not solely involve vesicle trafficking. In summary, our data demonstrate that the physical state of membrane lipids (fluidity) influences Na+/H+ exchange and may represent a physiological regulatory mechanism of NHE1 and NHE3 activity.