Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 181 records · Page 10Linked to original sources

PubMed1992

Soybean phospholipid dependent reductions in triacylglycerol concentration and synthesis in the liver of fasted-refed rats.

The effect of dietary soybean phospholipid on the activities of hepatic triacylglycerol-synthesizing enzymes was compared with soybean oil in fasted-refed rats. Soybean oil at the dietary level corresponding to 20% but not at 5% fatty acid level (21.2 and 5.3% on weight bases, respectively) significantly decreased liver microsomal diacylglycerol acyltransferase activities measured with the endogenous diacylglycerol substrate. Dietary soybean phospholipid even at the dietary level corresponding to 2% fatty acids (3.4% on weight base) significantly decreased the acyltransferase activities measured with endogenous substrate. The dietary phospholipid further decreased the parameter as the dietary level increased, and at the 5% fatty acid level, it was lower than that obtained with soybean oil at 20% fatty acid level. Soybean oil and phospholipid decreased the diacylglycerol acyltransferase activities measured with the saturating concentration of exogenous dioleoylglycerol substrate only when the activities were expressed in terms of total activity (mumol/min per liver) but to much lesser extents. Dietary phospholipid compared to the oil profoundly decreased not only hepatic triacylglycerol but also microsomal diacylglycerol levels. It was indicated that the availability of microsomal diacylglycerol as the substrate for diacylglycerol transferase is the critical determinant in regulating hepatic triacylglycerol synthesis and concentration in this experimental situation. Alterations in the activities of microsomal glycerol 3-phosphate acyltransferase and of the enzymes in fatty acid synthesis could account for the phospholipid-dependent decrease in the microsomal concentration of this intermediate in triacylglycerol synthesis.

Acyltransferases↗

PubMed1992

Cholesterol metabolism in ExHC (exogenous hypercholesterolemic) rats.

Exogenous hypercholesterolemic (ExHC) rats, that develop hypercholesterolemia for exogenous cholesterol, are an established strain Isolated from Sprague-Dawley (SD) rats by Imai and Matsumura ((1973) Atherosclerosis, 18, 59-64). The present study was carried out to clarify the cause of hyperresponsivity in ExHC rats to dietary cholesterol. As early as one day after feeding a high cholesterol diet (1%) serum cholesterol level was doubled in ExHC rats, while the level of hepatic cholesterol was two-thirds of SD rats. The elevation of serum cholesterol was mainly attributed to the d less than 1.006 g/ml fractions. Cholesterol feeding increased fecal bile acid excretion in both strains, but to a more greater extent in SD rats. Absorption of dietary cholesterol and synthesis of cholesterol in vivo were similar between the strains. The uptake of beta-very-low-density-lipoproteins (beta-VLDL) in vivo and the primary cultured hepatocytes was lower in ExHC rats, when a high-cholesterol diet was fed. Even without feeding of a high-cholesterol diet, preincubation with cholesterol-rich lipoproteins caused a lower association and degradation of beta-VLDL by the hepatocytes from ExHC rats. Incubation of hepatocytes with cholesterol-rich lipoproteins did not affect the secretion of [14C]cholesterol into the density less than 1.006 g/ml fraction, but suppressed the secretion into the medium density greater than 1.006 g/ml fractions. These results suggest that ExHC rats, as compared to SD rats, are defective of hepatic uptake and processing cholesterol to bile acids.

Animals↗

PubMed1992

5c,11c,14c-eicosatrienoic acid and 5c,11c,14c,17c-eicosatetraenoic acid of Biota orientalis seed oil affect lipid metabolism in the rat.

The effects of 5c,11c,14c-eicosatrienoic acid (20:3BSO) and 5c,11c,14c,17c-eicosatetraenoic acid (20:4BSO), polyunsaturated fatty acids (PUFA) contained in Biota orientalis seed oil (BSO), on lipid metabolism in rats were compared to the effects of fats rich in linoleic acid (LA) or alpha-linolenic acid (ALA) under similar conditions. The potential effect of ethyl 20:4BSO as an essential fatty acid also was examined in comparison with the ethyl esters of LA, ALA and gamma-linolenic acid (GLA). BSO- and ALA-rich fat decreased the concentration of plasma total cholesterol, high density lipoprotein cholesterol, triglyceride and phospholipid as compared to LA-rich fat. BSO was more effective in reducing plasma cholesterol concentrations than was the ALA-rich fat. Dietary BSO markedly decreased the hepatic triglyceride concentration as compared to the LA-rich or ALA-rich fats. Aortic production of prostaglandin I2 tended to decrease in rats fed BSO or ALA-rich fat compared to those fed the LA-rich fat. Adenosine diphosphate-induced platelet aggregation was similar in the three groups. The proportion of arachidonic acid (AA) in liver phosphatidylcholine (PC) of rats fed BSO was lowest compared to that of rats fed ALA-rich or LA-rich fats. Administration of 20:4BSO, ALA or GLA to essential fatty acid-deficient rats decreased the ratio of 20:3n-9 to AA in liver PC to the same extent; administration of LA was more effective. The results indicate that the effects of specific PUFA contained in BSO on lipid metabolism are different from those of LA and ALA. It is also suggested that 20:4BSO may exhibit some essential fatty acid effects.

Adipose Tissue↗

PubMed1992

Preserved mitochondrial function by allopurinol despite deteriorated hemodynamics in warm ischemia-damaged canine liver.

To investigate the pathophysiology of warm ischemia (WI) of the liver, the changes in hemodynamics and energy metabolism were studied during and after 60-min complete WI induced by total hepatic vascular exclusion (HVE) in the canine model. Hepatic arterial blood flow after WI was maintained at 76% of the pre-ischemic level, while portal blood flow was only 27% of the pre-ischemic level associated with increased portal vein pressure, which was twice the pre-ischemic level, resulting in a decrease of total hepatic blood flow to 46% of the pre-ischemic level. Concentration of tissue lipid peroxide increased after WI. Arterial blood ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, could not recover to the pre-ischemic level after termination of WI. However, when 100 mg/kg of allopurinol (xanthine oxidase inhibitor) was administered intravenously 10 min prior to initiating WI, AKBR was restored to the pre-ischemic level at 30 min after WI in spite of the fact that allopurinol administration to one group produced no remarkable changes in the hepatic hemodynamics compared with the group without allopurinol treatment. Concentration of adenine nucleotides was significantly higher for the treated group at the end of and after WI than for the group without allopurinol treatment and was maintained at a higher level even after WI. Lipid peroxide production was suppressed. Electron microscopic examination revealed that allopurinol treatment could not prevent mitochondrial swelling. It is suggested that WI causes injury primarily to the portal sinusoidal circulation, resulting in portal congestion concomitant with high portal pressure after the release of WI. Allopurinol could prevent the deterioration of mitochondrial ATP metabolism, and was able to inhibit lipid peroxide production, resulting in the rapid recovery of mitochondrial redox state in spite of the fact that it produced no amelioration of hepatic hemodynamics and morphological alterations.

Adenosine Triphosphate↗

PubMed1992

Effects of butyrate on cell cycle progression and polyploidization of various types of mammalian cells.

We studied the effect of butyrate on cell cycle progression and polyploidization in three fibroblast (rat 3Y1, human IMR-90, and human embryo lung HEL) and two epithelial (human embryo kidney HEK and monkey kidney BSC-1) cells. In these cells, except for 3Y1, G1 arrest with butyrate was incomplete, and the production of tetraploid cells was detectable in the presence of butyrate. G2 arrest with butyrate was also incomplete in HEL and BSC-1 cells, and the number of HEL cells increased in the presence of butyrate. On the contrary, most BSC-1 cells that divided in the presence of butyrate were unstable and the number of attached cells decreased. These results indicate that the effect of butyrate on cell cycle progression varies with the cell type and that polyploidization can be induced by a single treatment with butyrate.

Animals↗

PubMed1992

Effects of alpha-tocopherol and tocotrienols on blood pressure and linoleic acid metabolism in the spontaneously hypertensive rat (SHR).

Both alpha-tocopherol and a 1:1.7 mixture of alpha-tocopherol and tocotrienols at a 0.2% dietary level significantly depressed the age-related increase in the systolic blood pressure of spontaneously hypertensive rats (SHRs) after 3 weeks of feeding. The aortic production of prostacyclin was increased 1.5 times both by alpha-tocopherol and a tocotrienol mixture, suggesting a possible relevance to their hypotensive effect. These vitamins did not influence the delta 6- and delta 5-desaturase activities of liver microsomes, but fatty acid profiles of the liver phospholipids predicted a reduction of linoleic acid desaturation. These effects were in general more clear with tocotrienols than with alpha-tocopherol. Platelet aggregation by 5 microM ADP remained uninfluenced. Thus, tocotrienols may have effects on various lipid parameters somewhat different from those of alpha-tocopherol.

Animals↗

PubMed1992

Effects of cultured milk products by Lactobacillus and Bifidobacterium species on the secretion of bile acids in hepatocytes and in rats.

Whey preparations prepared from cultured milk by 19 Lactobacillus (2 species) and 20 Bifidobacterium (5 species) strains were examined for the effects of secretion and synthesis of bile acids in primary cultured rat hepatocytes. The stimulating effect of whey preparation on bile acid secretion depended on the species as well as the strains used for milk fermentation. Two strains belonging to L. casei SBT 2230 (LC2230) and B. longum SBT 2912 (BL2912) produced the whey which stimulates both the secretion of bile acid and the activity of cholesterol 7 alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis. When the cultured products by these two strains were given to rats for 14 days, the products from L. casei (LC2230) were found to stimulate the biliary secretion of bile acids. These results suggest that primary cultured hepatocytes were a useful experimental system as an initial screening for an active principle modulating cholesterol metabolism.

Animals↗

PubMed1992

Optic atrophy, sensorineural hearing loss and polyneuropathy--a case of sporadic Rosenberg-Chutorian syndrome.

We report on a 41-year-old woman with slowly progressive motor dominant polyneuropathy, optic atrophy and sensorineural deafness, but without any known familial feature. These neurological manifestations were in accordance with the syndrome reported by Rosenberg and Chutorian in 1967 (Rosenberg-Chutorian syndrome), a unique form of Charcot-Marie-Tooth disease. The syndrome was first reported to be autosomal dominant in trait, but subsequently recessive forms and sporadic ones have also been described. Nerve biopsy and neurophysiological studies including electromyography, nerve conduction velocities, somatosensory evoked potentials, auditory brainstem responses, and visual evoked potentials revealed the axonopathic involvement of the central nervous system as well as the peripheral nervous system. Since neurophysiological aspects of this particular syndrome have not been well studied, these results would provide some insight into the understanding of this disorder.

Adult↗

PubMed1992

[Necrotic plaque formation in a case of frontal lobe multiple sclerosis].

We reported an unusual case of multiple sclerosis (MS), clinical manifestations and neuroimagings of which were restricted to the frontal lobes and Gd-enhancing plaques on MRI later changed to necrotic lesions. A 36-year-old previously healthy man developed behavioral changes without any other neurological manifestations in a few weeks. Findings of magnetic resonance imaging (MRI) together with visual evoked potentials pointed to MS and corticosteroid pulse-dose therapy was initiated. Despite fairly uneventful, but rather delayed clinical recovery, repeated MRI disclosed rows of multiple, periventricular plaques localized to the bilateral frontal white matter and indicated the majority of lesions were not those of demyelination but necrosis. Frontal lobe syndrome is rarely encountered as a sole manifestation and rates only a few percent of MS cases in the literature. We speculated on the pathogenesis of necrotic plaques in this particular case; tumor necrosis factor, interleukin-1 and other cytokines that are known to be accompaniments of inflammatory cell infiltrates and activated glia in MS may ultimately destroy the CNS tissue, if the inflammation is not readily controlled. It is not certain, however, that what are determinants of demyelination and what drives further to the devastating tissue necrosis. Despite the uncertainty, this case indicates a necessity of immediate institution of adequate immunosuppressive therapy when neuroimaging study indicates active inflammation and openings of the blood-brain barrier in demyelinating plaques.

Adult↗

PubMed1991

Sesamin is a potent and specific inhibitor of delta 5 desaturase in polyunsaturated fatty acid biosynthesis.

Incubation with sesame oil increases the mycelial dihomo-gamma-linolenic acid content of an arachidonic acid-producing fungus, Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989) J. Am. Oil Chem. Soc. 66, 237-241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits delta 5 desaturase at low concentrations, but does not inhibit delta 6, delta 9 and delta 12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (Ki for rat liver delta 5 desaturase, 155 microM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin also inhibited only delta 5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of delta 5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.

Animals↗

PubMed1991

Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats.

The effects of various structured triglycerides containing medium-chain (caprylic or capric acids) and long-chain (linoleic acid) fatty acids on fatty acid and cholesterol absorption were studied in lymph-cannulated rats. A considerable portion of capric and caprylic acid was absorbed through the lymph duct, although to a lesser extent than was linoleic acid. Capric and linoleic acid located at the 2-position of 2-decanoyl-1,3-dilinoleoyl-glycerol (18:2/10:0/18:2) and 2-linoleoyl-1,3-didecanoyl-glycerol (10:0/18:2/10:0), respectively, tended to be absorbed more efficiently than those located at the 1- and 3-position or those from tricaprin (10:0/10:0/10:0) or trilinolein (18:2/18:2/18:2). A similar trend was observed when the medium-chain fatty acid was caprylic acid instead of capric acid. Caprylic acid absorption from 2-octanoyl-1,3-dilinoleoyl-glycerol (18:2/8:0/18:2) was significantly greater (p less than 0.05) than from 2-linoleoyl-1,3-dioctanoyl-glycerol (8:0/18:2/8:0) or tricaprylin (8:0/8:0/8:0). Preferential absorption of caprylic and linoleic acid was not observed when the 1 to 2 and the 2 to 1 mixtures of 8:0/8:0/8:0 and 18:2/18:2/18:2, respectively, were administered. The structured lipids did not affect the lymphatic absorption of cholesterol. The results suggest that structured triglycerides composed of medium-chain fatty acids and linoleic acid may be more useful for the treatment of lipid malabsorption than are mixtures of medium-chain triglyceride (MCT) and long-chain triglyceride (LCT).

Absorption↗

PubMed1991

Effects of oleic, arachidonic and 5,8,11,14-nonadecatetraenoic acids on lipid secretion and ketogenesis in perfused rat liver.

The effects of perfused oleic (18:1n-9), arachidonic (20:4n-6) and 5,8,11,14-nonadecatetraenoic (19:4n-5) acids on triglyceride and cholesterol secretion and ketone body production were studied in isolated rat liver. As compared to oleic and 19:4n-5 acids, both ketone body production and triglyceride secretion were significantly lowered when arachidonic acid was perfused. The concentration of triglyceride in the post-perfused liver was lower upon perfusion with arachidonic acid than upon perfusion with oleic acid or 19:4n-5 acid. Cholesterol secretion in the liver perfused with arachidonic acid or 19:4n-5 acid was significantly higher than with oleic acid. The concentration of cholesterol in the post-perfused liver was slightly but significantly higher with 19:4n-5 acid than with the other fatty acids. The results suggest that 19:4n-5 acid when compared with arachidonic acid affects lipid metabolism in liver differently.

Animals↗

PubMed1991

Effect of palm oil on lipid and lipoprotein metabolism and eicosanoid production in rats.

Palm oil (PA), which is very rich in palmitic acid, influenced the serum cholesterol concentration and tissue eicosanoid profile of rats characteristically. It increased the serum cholesterol concentration compared with safflower oil (SA), but the degree of the elevation was moderate compared with that of olive oil (OL). The proportion of arachidonic acid in tissue lipids was by no means lower on a PA diet than on an SA diet. The ratio of prostacyclin produced by the aorta to thromboxane A2 in plasma was not simply predicted by the dietary level of saturated fatty acid. PA tended to facilitate the utilization of arachidonate for prostacyclin in vitro in peritoneal macrophages compared with SA. Fatty acid profiles of PA rather than the glyceride structure or the tocotrienol appeared to be the major determinant for the specific features of lipid metabolism observed in rats fed PA.

Animals↗

PubMed1991

Interaction of dietary protein differing in sulfur amino acid content and pectin on bile acid conjugation in immature and mature rats.

Rapidly growing immature (4-wk-old) and slowly growing mature (15-wk-old) rats were fed fiber-free or 10 g/100 g pectin diets containing various proteins differing in the sulfur amino acid content for 30-32 d. Soybean protein, casein, whole egg protein and egg albumen were used at the nitrogen level of 2.7 g/100 g diet. These experimental diets contained 0.354, 0.540, 0.945 and 1.22 g sulfur amino acids/100 g, respectively. In the rats fed fiber-free diets, a substantial quantity of glycine-conjugated bile acids was detected in the bile of immature rats fed soybean protein and casein (73 and 25% of total bile acids, respectively), but not in the other groups (less than 13%). Dietary pectin increased bile acid excretion both in immature (48-77%) and mature (34-114%) rats irrespective of the protein source, except in immature rats fed egg albumen and mature rats fed whole egg protein. Because a pectin-dependent increase in bile acid excretion was essentially attributed to the increase in glycine-conjugates, this dietary fiber significantly increased the ratio of glycine-conjugates to taurine-conjugates (2.4- to 6.5-fold). This increase was accompanied by a 40-50% decrease in the concentration of liver taurine, except in immature rats fed soybean protein and egg albumen. However, there was no consistent relationship between the extent of taurine conjugation and the activity of liver cysteine dioxygenase, one of the rate-limiting enzymes in taurine synthesis.

Aging↗

PubMed1991

Reciprocal responses to exercise in hepatic ketogenesis and lipid secretion in the rat.

The effects of 4 weeks of voluntary exercise (rotating wheel) on serum and liver lipid levels were studied in 6-week-old male Wistar rats. The hypotriglyceridemic effect of exercise was not influenced by the dietary fat levels (4.5 and 14.5%), whereas the hypocholesterolemic effect was higher in a low-fat diet than in a high-fat diet. Although the serum cholesterol-lowering effect of exercise was marginal, the beneficial effect on hepatic lipids was observed only in rats fed a high-cholesterol diet. The hepatic contribution to the serum lipid-lowering action of exercise was examined in the isolated perfused livers of rats fed a low fat diet. The reduction (34%) of serum triglyceride by exercise corresponded to the decrease (32%) in the hepatic triglyceride secretion rate, indicating a significant role of the liver in the hypotriglyceridemic effect of exercise. In contrast, the decrease (31%) in serum total cholesterol was considerably greater than that (23%) in the hepatic secretion, suggesting an extra-hepatic contribution. On the other hand, the hepatic production of ketone body was increased by exercise. These results indicate that the altered hepatic partition of long-chain free fatty acids between esterification and oxidation is one of the causative factors for the serum lipid-lowering effect of exercise.

Animals↗

PubMed1991

Inhibitory effect of oral sorbent on accumulation of albumin-bound indoxyl sulfate in serum of experimental uremic rats.

Serum indoxyl sulfate, which is markedly accumulated in uremic patients, cannot be removed efficiently by hemodialysis due to its albumin binding. To determine if oral adsorbent (AST-120) can decrease its serum concentration in uremic state, oral adsorbent was administered to experimental nephrectomized uremic rats. Uremic rats fed with oral adsorbent showed a significantly lower serum concentration of indoxyl sulfate compared to control uremic rats, even when serum concentrations of urea nitrogen and creatinine were not significantly decreased in the uremic rats fed with oral adsorbent. Indoxyl sulfate was detected only at a lower concentration in bile as compared with the serum of uremic rats. These results suggest that oral adsorbent adsorbs indole, a precursor of indoxyl sulfate, in the intestine and prevents the accumulation of indoxyl sulfate in uremic rats.

Administration, Oral↗

PubMed1991

Dietary cholesterol influences on various lipid indices and eicosanoid production in rats fed dietary fat desirable for the protection of ischemic heart disease.

Young male Sprague-Dawley rats were fed diets containing 10% fat with P/S and n-6/n-3 ratios of 1.2 and 5.0, respectively, and differing levels of dietary cholesterol (0.05 to 1.0% by weight) for 3 weeks, following which the tissue lipid concentration, fatty acid composition, desaturation of linoleic acid, and eicosanoid production were examined. The composition of dietary fat was that recommended for the prevention of atherosclerosis. Dietary cholesterol did not largely influence the concentration of serum cholesterol, but it markedly increased liver cholesterol in a dose-dependent manner. The delta 6-desaturase activity in liver microsomes, linoleate desaturation index in liver phosphatidylcholine, and the production of prostaglandin by the aorta and thromboxane A2 by platelets all decreased to a similar extent in relation to dietary cholesterol above 0.2%. Thus, dietary cholesterol influenced various lipid parameters characteristically even when dietary fat with a fatty acid composition desirable for the prevention of atherosclerosis was consumed simultaneously. The dietary cholesterol level of 0.2% was the point of maximum influence in rats upon the indices examined.

Animals↗

PubMed1991

Inhibition of cholesterol absorption and synthesis in rats by sesamin.

The effects of sesamin, a lignan from sesame oil, on various aspects of cholesterol metabolism were examined in rats maintained on various dietary regimens. When given at a dietary level of 0.5% for 4 weeks, sesamin reduced the concentration of serum and liver cholesterol significantly irrespective of the presence or absence of cholesterol in the diet, except for one experiment in which the purified diet free of cholesterol was given. On feeding sesamin, there was a decrease in lymphatic absorption of cholesterol accompanying an increase in fecal excretion of neutral, but not acidic, steroids, particularly when the cholesterol-enriched diet was given. Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected the absorption of fatty acids. Only a marginal proportion (ca. 0.15%) of sesamin administered intragastrically was recovered in the lymph. There was a significant reduction in the activity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase after feeding sesamin, although the activity of hepatic cholesterol 7 alpha-hydroxylase, drug metabolizing enzymes, and alcohol dehydrogenase remained uninfluenced. Although the weight and phospholipid concentration of the liver increased unequivocally on feeding sesamin, the histological examination by microscopy showed no abnormality, and the activity of serum GOT and GPT remained unchanged. Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol simultaneously, it deserves further study as a possible hypocholesterolemic agent of natural origin.

Absorption↗