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Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 199 records · Page 11Linked to original sources
PubMed1991

Effect of an oral adsorbent (AST-120) in rats with daunomycin-induced chronic renal failure.

The effect of an oral adsorbent (AST-120) was examined in rats with daunomycin-induced chronic renal failure. Sixteen pairs of daunomycin rats which had similar levels of proteinuria at 4 weeks after being injected with daunomycin were selected. One rat of each pair served as a control and was fed on a standard diet, while the other rats were fed on a diet containing AST-120. The blood creatinine and blood urea nitrogen (BUN) were significantly lower in the rats fed with AST-120 than in the controls. Moreover, the life span of the rats fed with AST-120 was significantly prolonged as compared to that of the control rats. These findings suggest that oral administration of AST-120 may help to prevent rapid deterioration of renal function in experimental chronic renal failure induced by daunomycin in rats.

Administration, Oral↗
PubMed1990

Syntheses and platelet aggregation inhibitory and antithrombotic properties of [2-[(omega-aminoalkoxy)phenyl]ethyl]benzenes.

A series of [2-[(omega-aminoalkoxy)phenyl]ethyl]benzene derivatives were synthesized and evaluated for their ability to inhibit collagen-induced platelet aggregation in vitro and to protect experimental thrombosis in mice. The results showed that the compounds were in vitro inhibitors of collagen-induced platelet aggregation. Most of them were also effective in the mouse antithrombotic assay. The compounds were found to be potent antagonists to S2 serotonergic receptor, and good correlation (r = 0.85) between their S2 serotonergic receptor antagonism and their potency as platelet antiaggregatory drugs was observed. Among the compounds studied, mono[2-(dimethylamino)-1-[[2-[2-(3- methoxyphenyl)ethyl]phenoxy]methyl]ethyl] succinate hydrochloride (12b, MCI-9042) was selected for further pharmacological and toxicological evaluation.

Animals↗
PubMed1990

Cholesterol-lowering activity of various undigested fractions of soybean protein in rats.

The undigested high-molecular-weight fraction (HMF) of soybean protein prepared after exhaustive digestion by microbial proteases significantly decreased serum cholesterol levels to approximately 45% (p less than 0.05) of those observed with the parent protein in rats fed diets containing cholesterol (0.5%) and sodium cholate (0.125%). HMF bound conjugated bile salts in vitro and significantly increased fecal excretion of both neutral and acidic steroids by 65-95% and 80-170% more, respectively (p less than 0.05), than did the intact protein. Extraction of HMF with methanol slightly decreased the activity, but the methanol-soluble fraction was not regarded as a principal determinant. Soybean saponin at the dietary level equivalent to that contained in HMF did not effectively lower serum cholesterol. The activity was not necessarily duplicated even when methanol-treated fractions were recombined. Further degradation of the methanol-extracted HMF by various proteases resulted in loss of activity. HMF obtained after pepsin digestion exerted a potential similar to that of HMF prepared after digestion by microbial proteases.

Animals↗
PubMed1990

Effect of cholestyramine in early weaning on later response to serum and fecal steroid levels and cholesterol 7 alpha-hydroxylase activity to high-cholesterol diet in ExHC rats.

Male ExHC (exogenous hypercholesterolemic) rats were either prematurely weaned at 17 days of age or allowed to nurse until 35 days of age. The prematurely weaned rats were either fed a diet containing cholestyramine or cholestyramine-free diet until 35 days of age. Cholestyramine supplementation markedly increased fecal bile acid excretion and modified the composition. After giving a stock diet for 7 weeks, all rats received a cholesterol-enriched diet for 9 weeks. The serum cholesterol level in later time was not affected by early dietary manipulation. The activity of hepatic cholesterol 7 alpha-hydroxylase and fecal bile acid excretion at the end of the cholesterol challenge decreased in the cholestyramine-pretreated group, when compared to the normally weaned group. Fecal excretion and the ratio of the secondary (deoxycholic and lithocholic acids) to the primary (cholic and chenodeoxycholic acids) bile acids significantly decreased in the early cholestyramine-treated group. These results suggest that a modification of bile acid metabolism in early life may strongly influence the hepatic and possibly colonic bile acid metabolism in later life, when challenged with a high-cholesterol diet.

Animals↗
PubMed1990

Altered hepatic metabolism of free fatty acid in rats fed a threonine-imbalanced diet.

The effects of a threonine-imbalanced diet (8% casein supplemented with 0.3% methionine, TI) on the ketone body production and the secretion rate of lipids were examined in the isolated perfused rat liver. Feeding a TI diet compared to an 8% casein (C) diet resulted in an enlargement of liver, presumably due to 2-4-fold accumulation of triglyceride. Serum triglyceride likewise increased significantly in rats fed a TI diet. No significant difference was found in the other lipid components both in serum and liver. When the livers from rats fed C or TI diets were isolated and perfused in the presence of an exogenous oleate substrate, the TI diet decreased the ketone body production and conversely increased the secretion rate of triglyceride, suggesting an inverse relationship between rates of ketogenesis and triglyceride secretion. The proportion of oleate in the perfusate triglyceride obtained at the end of perfusion was comparable between the C and TI groups, whereas in the post-perfused liver it was higher in the former than in the latter, suggesting a stimulatory effect of the TI diet on the secretion of the oleate in the form of triglyceride. These results indicate that altered hepatic metabolism of long-chain free fatty acids between the pathways of oxidation and esterification is one of the causative factors for triglyceride accumulation in the liver produced by threonine imbalance.

Animals↗
PubMed1990

Steroid-binding peptides from dietary proteins.

The undigested high-molecular weight fraction (HMF) of soybean protein prepared after exhaustive digestion either by microbial proteases or by pepsin exerted a remarkable hypocholesterolemic activity compared to the parent protein in rats fed cholesterol-enriched diets. HMF bound in vitro with bile salts and stimulated fecal excretion of both neutral and acidic steroids far more than did soybean protein. Extraction of HMF with methanol slightly decreased the activity, but the methanol soluble fraction was not regarded as a principle determinant. Further degradation of the methanol-extracted HMF by various proteases resulted in loss of activity. Bile acid binding capacity of HMF from other vegetable proteins was lower than that form soybean protein.

Animals↗
PubMed1990

Effects of dietary protein levels and cholesterol on tissue lipids of rats.

The effects of the levels (10, 20, and 30%) of dietary proteins, soybean protein or casein, on various lipid parameters were examined in rats. The plasma cholesterol (CHOL) level tended to decrease with an increasing dietary protein level, in particular when diets contained CHOL. The hypocholesterolemic effect of soybean protein was evident with CHOL-enriched diets. The fecal excretion of acidic but not neutral steroids increased with an increasing protein level and it was higher in rats fed soybean protein than in those fed casein. The ratio of arachidonate to linoleate in plasma and liver phosphatidylcholine tended to increase with an increasing dietary protein level, although it was considerably higher in casein than in soybean protein diets. The results indicated that the hypocholesterolemic effect of soybean protein is influenced not only by the amount but also by the presence or absence of dietary CHOL. In addition, the degree of conversion of linoleate to arachidonate also depended on the type and level of dietary protein.

Animals↗
PubMed1990

Dietary protein influences polyunsaturated fatty acid patterns of rat tissue lipids.

Casein (CAS) promotes desaturation of linoleic acid (LA) in relation to soybean protein (SOY). This protein-effect could be detected within 4 days after feeding different proteins, and persisted even after overnight fasting. The difference was found irrespective of dietary fat even when delta 6-desaturation was depressed by alcohol consumption. The aortic production of prostacyclin (PGI2) was higher in the CAS group than in the SOY group irrespective of alcohol consumption. When the effect of lysine/arginine (Lys/Arg) ratio of dietary protein on LA desaturation was studied, the addition of Arg to CAS resulted in trend for the proportion of LA to increase and a arachidonic acid (AA) to decrease in liver phosphatidylcholine (PC). However, the effect of Lys addition was inconclusive. Thus, the content of Arg rather than the Lys/Arg ratio was at least one of the factors for the protein-dependent effect.

Animals↗
PubMed1990

Dietary fats modulate age-dependent effects of dietary proteins on cholesterol metabolism in rats.

Different aged male rats, 4 weeks or 9 months old, were fed diets containing either casein (CAS), milk whey protein (WHY) or soybean protein (SOY) with corn oil or sardine oil for 4 weeks. The hypocholesterolemic effect of SOY, compared to CAS, was more evident in rats fed corn oil than in those fed sardine oil, and in young rats than in adult rats, irrespective of dietary cholesterol. In contrast, the liver cholesterol-lowering effect of SOY was more marked in adult than in young rats in all experiments. WHY exerted an intermediate effect on the concentration of liver cholesterol. At both ages, the response of liver 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity was diverse and dependent upon the source of dietary fat and age of the animal. Fecal steroid excretion was significantly higher in rats fed SOY than in those fed either CAS or WHY, especially in adult rats. The results showed a diverse interaction of the protein type, fat and age in respect to lipid metabolism.

Aging↗
PubMed1990

Dietary protein as a regulator of lipid metabolism: state of the art and new perspectives.

August 28 and 29, 1989, a workshop entitled "Dietary protein as a regulator of lipid metabolism" was held in Fukuoka. This workshop highlighted the progress that has been made since 1909, the year that Ignatowski put forward that animal proteins in the diet can induce atherosclerosis in rabbits. It is now clear that humans respond to dietary soybean protein versus animal proteins, such as casein, with a decrease of serum cholesterol concentrations. However, the response in humans is not as pronounced as it is in various animal models. The mechanism by which the type of dietary protein affects serum cholesterol concentrations is still a matter of debate but various elegant concepts have been launched. These concepts have contributed significantly to our current understanding of the regulation of cholesterol metabolism. Future work will concentrate on further unravelling the mechanisms involved, with special reference to proteins other than those used generally, that is soybean protein and casein.

Animals↗
PubMed1990

[Effect of oral sorbent, AST-120, on serum concentration of indoxyl sulfate in uremic rats].

Indoxyl sulfate is a metabolite of tryptophan. Indole is synthesized in intestine from tryptophan by intestinal bacteria. The absorbed indole is converted to indoxyl sulfate through indoxyl in liver. Serum concentration of indoxyl sulfate is markedly increased as an inhibitor of drug-binding in uremic patients as compared with healthy subjects. Since indoxyl sulfate is bound to serum albumin, it cannot be removed efficiently by hemodialysis, and it tends to accumulate in uremic serum. To determine if oral sorbent, AST-120, could adsorb indole in intestine and then decrease serum concentration of indoxyl sulfate, it was administered to nephrectomized uremic rats. Serum concentration of indoxyl sulfate was markedly decreased in uremic rats fed with oral sorbent as compared with control uremic rats. However, serum concentrations of creatinine and urea nitrogen were not significantly decreased in the uremic rats fed with oral sorbent as compared with the control uremic rats. Serum concentration of tryptophan was not decreased but rather increased in the uremic rats fed with oral sorbent as compared with the control uremic rats. Concentration of indoxyl sulfate in bile of a uremic rat was much lower than that in the uremic serum, suggesting that the adsorption of indoxyl sulfate in intestine is not a major mechanism of decreasing the serum concentration of indoxyl sulfate. These results demonstrate that oral sorbent, AST-120, can decrease serum concentration of indoxyl sulfate in uremia due to adsorption of indole in intestine.

Administration, Oral↗
PubMed1990

Osseous changes and abnormalities of mineral metabolism in daunomycin rats.

We examined whether daunomycin rats could be used as an experimental model of human chronic renal failure in terms of their osseous changes and mineral metabolism. The daunomycin rats revealed hyperphosphatemia and osteodystrophic bone changes. In this respect, they were similar to human chronic renal failure. A high calcium level was found in the daunomycin rats at first due to the effect of the daunomycin injection, but later there was a lower calcium level than in the control rats due to chronic renal failure. We conclude that daunomycin rats can be successfully used as an experimental model of chronic renal failure from the standpoint of their osseous changes and mineral metabolism.

Animals↗
PubMed1990

[The effects of oral adsorbent (AST-120) in the experimental model of chronic renal failure--pathophysiological study on renal function, glomerular hypertrophy, mesangial function and glomerular histology].

Oral adsorbent (AST-120) reduces blood levels of urea and creatinine in experimental studies. It has also been shown to retard the progression of chronic renal failure in clinical studies. In the present study, the effect of AST-120 was examined in the rat model of subtotal nephrectomy (sNPX). This experimental model of chronic renal failure is characterized by glomerular hyperfunction, glomerular hypertrophy, increased mesangial trapment of macromolecules and subsequent glomerular sclerosis. We report the effect of AST-120 on glomerular hyperfunction, glomerular hypertrophy and mesangial trapment of macromolecules in the early stage and glomerular function and histology in the late stage of the rat model of sNPX. From 2 days after sNPX, rats were fed regular rat chow with (AST group: AST) or without (control) AST-120. At 2 weeks, iron dextran (ID) was injected intravenously. Three days after the injection, mesangial trapment of ID was largely ameliorated in AST when compared with control (p less than 0.02). The value of mean planar area of glomerulus (PAmean) in AST was significantly lower than that in control (p less than 0.05). At 2 and 9 weeks, the values of GFR and RPF in AST were all statistically higher than those in control. At 9 weeks, whereas average glomerular sclerosis index (SI: 0-4 scale) was 1.07 in control, significantly lower SI (0.57) was noted in AST (p less than 0.05). Thus, AST-120 has effects on glomerular hypertrophy, increased mesangial trapment of macromoleculus and finally the progression of chronic renal failure in the rat model of sNPX. The effects are not through reducing glomerular hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1990

[Daunomycin rats. Second Report. Is it possible to use daunomycin rats as an experimental model of chronic renal failure?].

We have previously reported that daunomycin rats can be used as an experimental model of chronic renal failure. We have since studied whether the result were reproducible by repeating the experiment. In this experiment we used larger numbers of rats and many more parameters of investigation compared with the previous experiment. The period of observation was extended to 42 weeks. Twenty-one female Wistar rats were given an injection of 12 mg/Kg of daunomycin into the jugular vein by the one-shot method. Ten control rats were injected with physiological saline. Eighteen daunomycin rats developed chronic renal failure within the observation period. Renal failure was confirmed by the levels of BUN and creatinine, the uremic peak 2a and the pathological findings. One rat died from a tumor and another rat died from thrombosis of the descending aorta. In only one rat was not at the level defined as chronic renal failure, although it was impaired even in this case. There was a correlation between the lifespan of the daunomycin rats and the amount of urine protein at 4 weeks. Rats with heavy proteinuria at 4 weeks died of uremia at an early age. There was a variety of evidence of daunomycin damage when rats were autopsied, not only in the renal glomeruli but also in the pancreas, liver and spleen. Some parts of the pancreas and liver showed vacuolated cells. We supposed that these various changes of many internal organs of daunomycin rats were secondary changes for chronic renal failure. We reconfirmed that daunomycin rats can be used as an experimental model of chronic renal failure.

Animals↗
PubMed1989

Effect of phosphatidylethanolamine and its constituent base on the metabolism of linoleic acid in rat liver.

Dietary phosphatidylethanolamine (PE) contributes the circulatory and hepatic free-ethanolamine in rats (Ikeda et al. (1987) Biochim. Biophys. Acta 921, 245). A role for circulatory ethanolamine has not been defined; however, our recent studies have shown that exogenous ethanolamine influences cholesterol and linoleic acid metabolism in rats (Imaizumi et al. (1983) J. Nutr. 113, 2403). In order to understand the role of dietary PE the effects of PE and its base on the hepatic metabolism of linoleic acid were investigated in vivo and in primary cultured hepatocytes in rats. Dietary PE increased the plasmic level of ethanolamine from 37 to 52 microM and decreased the ratio of arachidonate to linoleate in hepatic phospholipids. Activity of hepatic delta 6-desaturase decreased in rats given PE and the desaturation of [14C]linoleate in the cultured hepatocytes decreased by the addition of ethanolamine. Secretion [14C]linoleate labeled very-low-density lipoprotein from the cultured hepatocytes decreased by the addition of ethanolamine. Dietary PE caused an increased formation of CO2 from [14C]acetate by liver slices, and ethanolamine added to the hepatocytes caused an increased oxidation of [14C]linoleate and a suppression of fatty acid synthesis from [3H]serine. These results suggest that ethanolamine derived from the dietary PE plays a regulatory role in the linoleate metabolism in the liver.

Animals↗
PubMed1989

The combined effects of dietary proteins and fish oil on cholesterol metabolism in rats of different ages.

Male Sprague-Dawley rats at the ages of four weeks and nine months were fed purified diets containing 20% proteins either as casein (CAS), milk whey protein (WHY), or soybean protein (SOY) with 5% sardine oil for four weeks. The hypocholesterolemic effect of SOY was not statistically evident as compared to milk proteins at both ages, although serum cholesterol tended to be low in the SOY groups. A significant age-dependent increase in serum cholesterol was observed in all dietary groups. Liver cholesterol concentrations were comparable in young rats, whereas in adults they were significantly lower in the SOY than in the CAS or WHY groups. At both ages, the activity of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase tended to be higher in the SOY than in the other groups. Fecal steroid excretion was significantly higher in rats fed SOY than those fed either CAS or WHY, especially in adult rats. Significant age- and dietary protein-effects were observed in fatty acid profiles of liver microsomal phospholipids. Thus, the effects of dietary proteins on various lipid parameters were essentially maintained even when fish oil served as the source of dietary fat.

Age Factors↗
PubMed1989

Effect of dietary n-3 polyunsaturated fatty acids on cholesterol synthesis and degradation in rats of different ages.

Male Sprague-Dawley rats four weeks or eight months of age were fed purified diets containing 10% fat, either as a blend of safflower oil and palm olein (polyunsaturated fatty acids, PUFA, 34%), a blend of linseed oil and palm olein (PUFA, 33%) or sardine oil (PUFA, 33%) for four weeks. In other trials, sterol contents were made equivalent by supplementing cholesterol to a blend of corn oil and palm olein (PUFA, 30%) or phytosterol to sardine oil (PUFA, 30%). Fish oil was hypolipidemic in rats of different ages, but it tended to increase liver cholesterol in adult animals and this was not improved by the addition of phytosterol. The age-dependent increase in liver cholesterol was not duplicated in rats fed a vegetable fat blend supplemented with cholesterol. At both ages, liver 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was lower in the sardine oil than in the other groups. There were no significant age- or diet-related differences in the activity of liver cholesterol 7 alpha-hydroxylase. Fecal steroid excretion was comparable in age-matched rats fed diets supplemented either with cholesterol or phytosterol. Sardine oil reduced the delta 6-desaturase activity markedly as compared with linseed oil, and age-dependent reduction of the desaturase activity was observed in all dietary groups examined. Thus, the results showed a specific effect of fish oil on lipid metabolism.

Age Factors↗