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Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 235 records · Page 13Linked to original sources
PubMed1988

Effects of diltiazem on suppression and regression of experimental atherosclerosis.

The effects of diltiazem (a calcium antagonist) on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet together with saline (n = 22) or diltiazem (n = 9) injections. After 10 weeks, seven rabbits that received saline and nine rabbits that received diltiazem were killed. The remaining 15 saline-treated rabbits were then put on a standard (regression) diet for the next 15 weeks with saline (n = 7) or diltiazem (n = 8) injections. Sixteen rabbits given a standard diet were used as controls. At 5 and 10 weeks, the plasma LDL cholesterol level in rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline. The aortic total cholesterol, esterified cholesterol and calcium contents were also significantly lower in rabbits on the atherogenic diet with diltiazem. After 25 weeks (15 weeks on the regression diet), the differences in aortic total cholesterol and calcium contents between the two groups on the regression diet were not significant; however, the aortic esterified cholesterol content was significantly lower in the regression diet with diltiazem. The results suggest that diltiazem has a favourable effect both on regression and on suppression of atherosclerosis.

Animals↗
PubMed1988

Discrimination between cholesterol and sitosterol for absorption in rats.

The intestinal absorption of cholesterol and sitosterol was compared in rats. The intragastric administration of a single emulsified lipid meal containing either 50 mg of [4-14C]cholesterol or [4-14C]sitosterol resulted in the lymphatic absorption of 18.2% and 0.42% of each sterol, respectively, in 6 hr. This difference was unaltered when the mucosal sterol load was equalized by reducing the cholesterol to 1 mg in the emulsified lipid meal while maintaining the same sitosterol load or when the physical state in the lumen was equalized by infusion of a micellar solution containing both sterols into bile-diverted intestine. Lymphatic cholesterol was 90% esterified compared to 12% for sitosterol. Both sterols were associated predominantly (greater than 70%) with the chylomicron fraction. Eighty percent of the chylomicron cholesterol was recovered as ester with the core lipids, while 77% of the sitosterol was recovered as free sterol with the chylomicron coat. In mucosal homogenates at 6 hr, sitosterol recovery was one-eleventh that of cholesterol. When [3H]cholesterol (10 mg) and [14C]sitosterol (10 mg) were co-administered in an emulsified intragastric lipid meal, sitosterol associated with the brush border isolated 2 hr later was one-fifth that of cholesterol. Similar differences were seen when brush border membranes were incubated in vitro with micellar solutions containing either 50 microM [3H]cholesterol or [14C]sitosterol and the relative uptake of each sterol was unaffected by micellar phospholipid type (egg yolk phospholipids, phosphatidylcholine, or phosphatidylethanolamine).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Absorption and transport of base moieties of phosphatidylcholine and phosphatidylethanolamine in rats.

The absorption and transport of the base moieties of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) which were fed to rats were compared. The major absorption site of ethanolamine-labeled PE was proximal jejunum while choline-labeled PC was absorbed almost equally throughout the jejunum. Lysophospholipids, glycerophosphoryl bases and constituent bases were the main digested products in intestinal content. This shows that base-labeled phospholipids were hydrolyzed to water-soluble products as well as lysophospholipids before absorption. The radioactivities from both phospholipids existed mainly in their parent phospholipids and water-soluble products in the intestinal mucosa. The amounts of lymphatic transport of the radioactivities from choline-labeled PC and ethanolamine-labeled PE were 17% and 8%, respectively, at 8 h after administration. The liver in lymph-cannulated rats contained 23% and 48% radioactivity from PC and PE, respectively, suggesting that base moieties of phospholipids, especially PE, were transported mainly via a non-lymphatic route, probably the portal vein, to the liver, as water-soluble products. The radioactivity from both base-labeled phospholipids in the liver was distributed in the parent phospholipids and water-soluble fractions. Ethanolamine-labeled PE was also incorporated into PC in the liver. These results indicate that intestinal absorption and transport of the base moiety of dietary PC and PE are similar; however, their intestinal absorption site and the extent of their separation during transport between the lymphatic and portal systems differ markedly.

Animals↗
PubMed1987

Di(2-ethylhexyl)phthalate enhances hepatic phospholipid synthesis in rats.

The effects of di(2-ethylhexyl)phthalate, a typical peroxisomal proliferator, on the activities of key enzymes in the glycerophospholipid synthetic pathway and the incorporation of lipid precursors into liver lipids in vitro were studied periodically in rats. When di(2-ethylhexyl)phthalate was fed at the 1% level to rats, glycerol-3-phosphate acyltransferase activity increased 2-3-fold in liver homogenates and microsomes in 2-4 days. The specific activity of microsomal CTP:phosphocholine cytidylyltransferase increased by 1.5-fold, whereas the cytosolic activity was depressed. The microsomal CDPcholine:diacylglycerol cholinephosphotransferase specific activity decreased, whereas the activity in the homogenates increased, suggesting the proliferation of the hepatic endoplasmic reticulum in di(2-ethylhexyl)phthalate-treated rats. The incorporation of [1(3)-3H]glycerol or [1-14C]acetate into liver phospholipids in vitro increased in 2 days and stayed at a high level up to 12 days. The present study confirmed that di(2-ethylhexyl)phthalate induced an enhancement of phospholipid synthesis in the liver. The increase in hepatic phospholipid synthesis by this drug is presumably linked to the proliferation of peroxisomes and other intracellular membranes.

Acetates↗
PubMed1987

Characterization of serum apolipoprotein patterns in rats during suckling and post-weaning periods.

Changes of serum apolipoprotein patterns during the suckling and post-weaning periods were studied in rats. Concentrations of apolipoprotein A-IV and the high-molecular-weight form of apolipoprotein B were markedly high during the early suckling periods and decreased at weaning. Secretion of apolipoprotein A-IV into the mesenteric lymph in 2-week-old rats was as high as that in adult rats into which the high-fat diet was infused constantly. Apolipoprotein A-IV was found both in high-density lipoprotein and lipoprotein-free fractions, and the relative distribution in the latter decreased developmentally. The concentration of apolipoprotein A-I was low for 1 week after birth, after which it increased to the adult level. The apolipoprotein E level during the suckling and post-weaning periods was similar to or above that of adult rats. The newly formed apolipoprotein B in very-low-density lipoproteins secreted by the isolated liver and by the primary culture hepatocytes of suckling rats was predominantly a high-molecular-weight form. Overnight fasting and early weaning caused a remarkable alteration of the serum apolipoprotein profile. It therefore appears that frequent ingestion of dam's milk as well as ontogenic development are relevant to the serum apolipoprotein patterns characteristic for suckling rats.

Aging↗
PubMed1987

Activities of liver mitochondrial and peroxisomal fatty acid oxidation enzymes in rats fed trans fat.

The effect of trans fat on the activities of liver mitochondrial and peroxisomal fatty acid oxidation enzymes was examined in various strains of rats. When Wistar and Sprague-Dawley rats were fed for 30 days diets containing either olive oil or partially hydrogenated corn oil as a source of cis- or trans-octadecenoate, respectively, the activities of various enzymes of mitochondrial and peroxisomal beta-oxidation measured with cis- and trans-9-octadecenoic acid as substrates showed little dietary fat-dependent change. In Fischer 344 rats, feeding trans fat for 15 mo increased only moderately various enzymes of beta-oxidation except for carnitine acyltransferase. The rate of mitochondrial ketogenesis and the activity of carnitine acyltransferase measured with trans-9-octadecenoic acid as a substrate were about half those with the cis-counterpart. Peroxisomes oxidized trans-9-octadecenoyl-CoA at a rate comparable to the cis-counterpart. It was concluded from this study and previous ones that the difference in the geometry of dietary fatty acid had only a marginal effect in modulating the hepatic fatty acid oxidation system, in spite of marked differences in the metabolic behavior of cis- and trans fatty acid in cell-free preparations and perfused liver.

Animals↗
PubMed1987

Alteration of hepatic phospholipids in rats and mice by feeding di-(2-ethylhexyl)adipate and di-(2-ethylhexyl)phthalate.

Effects of di-(2-ethylhexyl)adipate (DOA) and di-(2-ethylhexyl)phthalate (DEHP), plasticizers for polyvinylchloride products, on concentrations and compositions of hepatic phospholipids were studied in rats. When administered to rats at a 2% level for 2 wk, both DOA and DEHP caused a hepatomegaly, an increase in hepatic phospholipids and a decrease an increase in hepatic phospholipids and a decrease in the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE). In the comparable study with mice, the alkyl moiety of DOA was found to be responsible for these alterations. DOA and DEHP specifically altered fatty acid compositions of PC and PE: there was an increase in oleic and palmitic acids and a decrease in stearic and docosahexaenoic acids in PC and an increase in arachidonic acid at the expense of docosahexaenoic acid in PE. In addition, DOA caused an increase in the trienoic and tetraenoic molecular species in PC and an increase in the 1-palmitoyl-2-arachidonyl (16:0@20:4) species in PE. Thus, the effects of DOA on the lipid dynamics resembled those observed with DEHP, although the magnitude was slightly moderated.

Adipates↗
PubMed1987

Effects of short-term cholestyramine feeding on cholesterol metabolism in differently aged rats.

The effects of short-term (7 days) feeding of a diet containing cholestyramine (5%) on the cholesterol metabolism were studied in male Sprague-Dawley rats at ages of 5 weeks (young) and 9-10 months (adult). Cholestyramine significantly enhanced the activities of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase both in young and adult rats; however, the absolute values were significantly higher in the former. The time-courses of changes in the activities of these enzymes after cessation of cholestyramine were comparable in both groups of rats. The rate of incorporation of mevalonate into sterol was also higher in young than in adult rats, while the stimulating effect of cholestyramine was markedly greater in adult rats. Hepatic acyl-CoA:cholesterol acyltransferase activity was comparable, but cholestyramine significantly decreased it only in adult rats. In adult rats hepatic cholesterol was decreased significantly by the resin while it remained uninfluenced in young rats. The serum cholesterol level tended to be higher in adult rats regardless of the dietary manipulation. The results indicate an appreciable age-dependent change in the hepatic cholesterol metabolism in response to the interruption of enterohepatic circulation of bile acids.

Aging↗
PubMed1987

Purification of horse (Equus caballus) serum lecithin:cholesterol acyltransferase.

1. A method for the purification of horse serum lecithin:cholesterol acyltransferase has been established. 2. The method involves the adsorption of the enzyme from diluted horse serum on DEAE-Sephadex A-50, (NH4)2SO4 fractionation, 1-butanol treatment, and chromatographic techniques of DEAE-Sepharose CL-6B, DEAE-Sephadex A-50, Affi-Gel blue and hydroxylapatite. 3. The resultant enzyme preparation essentially formed a single main band when subjected to polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. 4. The final purification of the enzyme was 20,000-fold with 7% yield. 5. The apparent mol. wt of the enzyme was 64,000. 6. The activity of the enzyme was stable for 3 days at 0 degree C.

Animals↗
PubMed1987

Age-related changes in the regulation of cholesterol metabolism in rats.

Activities of the hepatic cholesterol synthetic system including initial steps of the pathway and cholesterol 7 alpha-hydroxylase were all lower in adult (8 to 9-month-old) rats than in young (5 week-old) rats. The extent of diurnal fluctuation of 3-hydroxy-3-methylglutaryl coenzyme A reductase was, however, apparently greater in adult animals. When the cholesterol-enriched diet was fed to rats for 1 day, the extent of the depression of the cholesterogenic enzymes was dependent on age of animals. The enzyme activities rapidly increased on refeeding a cholesterol-free diet after the cholesterol challenge. In young rats the activity of cholesterol 7 alpha-hydroxylase exhibited a pattern inverse to that of HMG-CoA reductase whereas in adult rats it increased continuously during the entire experimental period. Cholesterol and triglyceride accumulated in the liver of adult animals, and their response to dietary cholesterol also depended on the age of the animals. The results indicate a specific modification of the cholesterol homeostatic mechanism with age.

Aging↗
PubMed1987

Effects of a new alpha 1-blocker, bunazosin hydrochloride, on plasma lipid components in hypertensive patients with hypercholesterolemia.

Oral bunazosin hydrochloride, a new alpha 1-blocker, for 12 weeks was given to ten outpatients diagnosed as having essential hypertension associated with hypercholesterolemia. High-density lipoprotein (HDL) triglyceride, HDL3 cholesterol, and apolipoprotein E levels were significantly decreased by bunazosin treatment. The decrease in HDL triglycerides was a result of the decrease in HDL3 triglyceride levels. There were no significant changes in the other components. The ratio of cholesterol to triglycerides in the low-density lipoprotein (LDL) and HDL fractions was increased significantly after bunazosin treatment. Furthermore, the ratio of HDL2 cholesterol to HDL3 cholesterol after bunazosin treatment was significantly higher than before treatment. The results suggest that the catabolism of triglycerides in lipoprotein and the reduction in tissue cholesterol increase, and that bunazosin hydrochloride does not adversely affect the lipid component in hypertensive patients with hypercholesterolemia.

Adrenergic alpha-Antagonists↗
PubMed1987

Suppression of atherogenesis in hypercholesterolemic rabbits by chondroitin-6-sulfate.

The effect of chondroitin-6-sulfate, obtained from shark cartilage, on atherogenesis in rabbits fed a high-cholesterol diet was studied. Male Japanese white rabbits were housed for 10 weeks in three groups, one group was fed ordinary pellets and was injected intraperitoneally with saline (standard-diet group), one was fed pellets containing 1% cholesterol and was injected intraperitoneally with saline (cholesterol-diet group), and the third group was fed pellets containing 1% cholesterol, and was injected intraperitoneally with 10 mg of chondroitin-6-sulfate (C-6-S group). Injections were done daily. The plasma total cholesterol, and cholesterol from very low-density lipoprotein in the C-6-S group after 5 weeks in the test period, and low-density lipoprotein cholesterol in the C-6-S group at the end of the test period were lower than those of the cholesterol-diet group. Significantly fewer atherosclerotic lesions of the aortic surface were found macroscopically in the C-6-S group than in the cholesterol-diet group. The cholesterol, esterified cholesterol and calcium concentrations of the aortic intima-media in the C-6-S group were significantly lower than in the cholesterol-diet group. Hydroxyproline levels in these three groups were not different. The uronic acid concentration of the intima-media in the cholesterol-diet group was significantly higher than in the C-6-S group (P less than 0.02). Though the percentage of heparan sulfate on total glycosaminoglycans (GAGs) of the C-6-S group was lower than in the cholesterol-diet group, there were no significant differences in the percentages of dermatan sulfate and chondroitin-4/6-sulfate in total GAGs between the cholesterol-diet and C-6-S groups. These results suggest that chondroitin-6-sulfate suppresses cholesterol deposition in the aorta of rabbits fed a 1% cholesterol diet, probably partly due to a decrease in the plasma low-density lipoprotein cholesterol, and partly due to a change in arterial metabolism.

Animals↗
PubMed1986

Strain dependence of the metabolism of cis- and trans-isomers of 9-octadecenoic acid in perfused liver and cell-free preparation in rats.

Hepatic metabolism of cis- and trans-9-octadecenoic acid was compared in various strains of rats and under different nutritional states. In Wistar rats triacylglycerol secretion was consistently higher in livers perfused with the cis isomer than with the trans isomer, while the difference was considerably attenuated in Sprague-Dawley rats. The difference in the hepatic triacylglycerol secretion disappeared when rats were fasted for 2 days. The rate of oxidation of trans fatty acid to ketone bodies was remarkably much higher than the cis isomer in Wistar but not in Sprague-Dawley rats. After fasting, the difference in the ketone body production disappeared in Wistar rats, whereas the oxidation rate was rather lower in the trans isomer than in the cis isomer in Sprague-Dawley rats. In isolated mitochondria, ketogenesis from trans-9-octadecenoic acid was markedly lower than that from the cis counterpart, irrespective of the nutritional states or strains of rats, and correlated well with the substrate specificity of carnitine acyltransferase. The molar concentration of malonyl-CoA to cause 50% inhibition of ketogenesis, the rate of peroxisomal beta-oxidation and the activity of acyl-CoA oxidase were all comparable, irrespective of the substrate sources. The Km value for acyl-CoA oxidase to the trans-acyl-CoA was 2-times higher than that of the cis counterpart in both strains of rats. Thus, peroxisomal as well as mitochondrial fatty acid oxidation systems apparently discriminated between the geometrical differences of the fatty acid substrate.

Acyl-CoA Oxidase↗