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Biomedical subjects

C Sugawara

Publications and source records attributed to C Sugawara.

At least 37 records · Page 2Linked to original sources
PubMed1994

Role of hepatic copper-metallothionein on liver function of Long-Evans cinnamon rats with a new mutation causing hereditary hepatitis.

Liver slices from Wistar and Long-Evans Cinnamon (LEC) rats were incubated while open to the atmosphere to assess the liver function in LEC rats. Leakages of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) into the medium were significantly lower in the LEC rat than in the Wistar rat. Furthermore, no pronounced enhancement of the concentration of thiobarbituric acid-reactive substances (TBARS) was found in the LEC rat. Hepatic Cu and Cu-metallothionein (Cu-MT) concentrations were 355.0 +/- 18.7 micrograms/g liver and 2559 +/- 181 micrograms/g protein in the LEC rats, whereas Wistar rats showed 4.1 +/- 0.1 Cu microgram/g liver accompanied by 16 +/- 4 micrograms/g protein of MT. The decrease of intrahepatic Cu-MT in LEC rats was stimulated by incubation with Fenitrilotriacetate (Fe-NTA). There was a direct correlation between the enhancement of TBARS and disappearance of Cu-MT. Our results suggest that hepatic Cu-MT in LEC rats protects against liver injury stimulated by oxidative stress.

Animals↗
PubMed1993

Decrease in biliary excretion of copper in Long-Evans cinnamon (LEC) rats causing spontaneous hepatitis due to a gross accumulation of hepatic copper.

The concentration of biliary Cu was 0.12 +/- 0.01 microgram/ml in male LEC rats aged 14 weeks and 0.43 +/- 0.09 micrograms/ml in Fischer rats of the same age. When copper chloride (170 micrograms/kg b.w. as Cu) was infused intravenously (i.v.), the concentration of biliary Cu increased to only 0.21 +/- 0.06 microgram/ml 30 min after the infusion in LEC rats. In contrast, Fischer rats showed a concentration about 10 times higher (4.02 +/- 2.2 micrograms/ml) than that before the infusion. In Fischer rats pretreated with cadmium chloride, the biliary Cu concentration was 1.04 + 0.43 micrograms/ml 30 min after infusion of copper. Horseradish peroxidase (E.C.1.11.1.7) infused iv along with copper chloride was excreted into bile at a low level in LEC rats compared to Fischer rats. Our results suggest that the gross accumulation of hepatic Cu in the new, mutant LEC rats is due to a low excretion of Cu into bile and that the hepatobiliary dysfunction is related to spontaneous hepatitis.

Animals↗
PubMed1992

Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis.

In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu concentrations increased in 7 regions, in particular, significantly so in the striatum, hypothalamus, cerebellum, midbrain and cortex. Changes of Zn concentration were not found in any region. The Fe concentration increased in cortex and olfactory lobes. The three LEC groups showed a very high concentration of hepatic Cu and a low concentration of serum Cu compared to LEA rats. In LEC rats aged 32 weeks, however, hepatic Cu decreased and serum Cu increased compared to the other two LEC groups. These results suggest that the increase of the cerebral Cu concentration is closely related to the inherently abnormal Cu metabolism and then to the changes of Cu metabolism from about 13 weeks after birth.

Animals↗
PubMed1992

The effects of aluminum ingestion on intestinal cadmium absorption, lipid peroxidation and alkaline phosphatase activity.

Consumption of dietary aluminum (A1, 2000 or 4000 ppm) for 1 month did not influence mouse body weight. In order to estimate an absorption of cadmium (Cd) from the gastrointestinal tract, mice were intubated twice every 24 h with Cd (CdCl2). In the A1-supplemented mice, Cd absorption increased rather than decreased. Intestinal Cd and metallothionein concentrations were increased by the A1 supplement. Intestinal alkaline phosphatase activity and lipoperoxide concentrations were also enhanced by A1 ingestion. Of course, intestinal A1 concentration was at a high level in the A1-supplemented groups. However, A1 accumulation was not observed in the liver. The increase of Cd absorption may be due to an abnormality of the gut wall caused by the A1. Our results suggest that A1 is not inert for animals, even though A1 absorption is poor.

Administration, Oral↗
PubMed1992

Excessive accumulation of hepatic copper in LEC rats aged 80 days without hepatitis and 130 days with hepatitis.

The Cu concentration was about 40 and 60 times higher in the liver in Long-Evans with a cinnamon-like coat color (LEC) rats aged 80 days (without hepatitis) and 130 days (with hepatitis), respectively than in the liver in Fischer rats. Most hepatic Cu was recovered in the cytosol fraction. Furthermore, about 96% and 84% of the cytosolic Cu was found in the metallothionein region on a Sephadex G-75 column in LEC rats aged 80 and 130 days, respectively. The hepatic metallothionein concentration was about 130 to 140 times higher in LEC rats than in Fischer rats when the concentration was expressed as metallothionein-bound Cu. Three forms of Cu-metallothionein were isolated by DEAE-cartridge. Although the concentration of hepatic Cu-metallothionein and its composition of polymorphic form were not changed greatly in hepatitis phase (in the 130-day-old LEC rats), activities of serum enzymes, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) were increased significantly. The LEC rat showed a significantly low concentration of biliary Cu and markedly low activity of ceruloplasmin (as ferroxidase). Serum Cu showed a low concentration in the 80-day-old LEC rats, but recovered to the control level in the 130-day-old LEC rats. The abnormal accumulation of Cu may be due to the inherent reduction of excretion of Cu into the bile and blood. Such deposition may be a trigger for the onset of the spontaneous hepatitis occurring at 90-120 days after birth and for the onset of hepatoma later.

Animals↗
PubMed1992

Copper metabolism in new mutant Long-Evans cinnamon (LEC) rats causing hereditary hepatitis: gastrointestinal absorption and distribution of radioisotopic copper (64Cu).

Long-Evans cinnamon (LEC) rats 60 days old showed a concentration of 127.7 +/- 10.9 micrograms/g of Cu in the liver, compared to 1.6 +/- 0.1 micrograms/g in Fischer rats 60 days old. At 2 hr after an oral injection of 64Cu, total retention of 64Cu in the whole blood, liver and kidneys was 16.8 +/- 3.4% of the dose in LEC rats, compared to 13.1 +/- 1.3% in Fischer rats. The recovery rates of retained-64Cu in the livers in LEC and Fischer rats were 82% and 59%, respectively. More than 90% and about 60% of hepatic 64Cu existed in the cytosol fraction in LEC and Fischer rats, respectively. Furthermore, more than 90% of the cytosolic 64Cu was found as MT in LEC rats. In Fischer rats, this proportion was about 60%. In the duodenum mucosal cytosol fraction from LEC rats, about 50% of 64Cu was bound to metallothionein (MT) protein. In Fischer rats, this proportion was less than 20%. When a 64Cu compound was intraperitoneally injected, 70% and only 15% were recovered in the liver 20 hr after the injection in LEC and Fischer rats, respectively. Furthermore, LEC rats showed very low 64Cu activity in the serum, and their duodenal activities were slightly low compared to Fischer rats. These results suggest that the gross accumulation of hepatic Cu is mainly due to deficient excretion of Cu from the liver.

Animals↗
PubMed1991

Copper metabolism in the LEC rat: involvement of induction of metallothionein and disposition of zinc and iron.

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5 +/- 21.6 micrograms/g liver) than in Fischer rats (5.2 +/- 0.1 microgram/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.

Animals↗
PubMed1991

Gastrointestinal absorption of Cd-metallothionein and cadmium chloride in mice.

CdCl2 or Cd-metallothionein (MT) (6 micrograms Cd with 2.25 muCi (83.25 KBq) 109Cd) was given orally to mice, which were sacrificed at 30 min and 2 h after intubation. Although 109Cd in Cd-MT was excreted rapidly into the urine, its absorption was found to be significantly less than that of CdCl2. The poor absorption was due to a decrease of Cd-MT uptake into the intestine. Cadmium chloride taken up into the mucosa could stimulate MT synthesis even 30 min after its intubation. However, the percentage of MT-bound Cd in the Cd of intestinal supernatants was lower with CdCl2 (62% at 30 min and 2 h) than with Cd-MT (78% and 84% at 30 min and 2 h, respectively). These results suggest that the transport mode of lumenal Cd-MT to mucosal cells is different from that of lumenal CdCl2. Lumenal Cd-MT is probably internalized into intestinal cells in an intact form. Furthermore, the Cd-MT may pass through the basolateral membrane in this form. This hypothesis was supported by the different distributions of Cd in the liver and kidney after Cd-MT and CdCl2 intubations.

Animals↗
PubMed1991

Copper metabolism in LEC rats aged 30 and 80 days old: induction of Cu-metallothionein and status of zinc and iron.

In 30- and 80-day-old LEC rats, hepatic Cu and Cu-metallothionein (MT) concentrations were much higher than those in control Fischer rats. The gross deposition was accompanied with enhancements of Zn and Fe concentrations. In LEC rats, more than half of the hepatic Cu was located in the cytosol fraction. Most of cytosolic Cu was bound to MT. In organs other than the liver, sharp depositions of Cu were not found. Both groups of LEC rats showed significantly low serum Cu concentrations and ceruloplasmin activity. The great accumulation of hepatic Cu with the increase of age is due to the inherent depression of the release of Cu from the liver. The deposition may be closely related to the onset of the sudden hepatitis observed in LEC rats.

Aging↗
PubMed1991

Harmful effect of administration of copper on LEC rats.

When four male LEC rats aged 80 days old were given 3.0 mg/kg of Cu once every day for 3 days, all rats showed severe jaundice, and two of them died within 48 hr after the final dose. In Fischer rats given Cu, jaundice or death was not found. With the injection of Cu, the Cu metabolism of Fischer and LEC rats showed different responses. In particular, the concentration of hepatic Cu increased only slightly in LEC rats. Furthermore, LEC rats did not respond to the release of ceruloplasmin to the blood and of Cu to the bile. These results suggest that Cu was very dangerous for LEC rats because of its gross accumulation over the level of homeostasis.

Animals↗
PubMed1991

Distribution of Cu and induction of Cu-metallothionein in mice treated with Cu-nitrilotriacetic acid.

Slightly higher levels of copper were incorporated into the liver in copper-nitrilotriacetic acid (Cu-NTA)-treated mice than in CuSO4-treated mice. There was no difference in the distribution of Cu in hepatic subfractions between the two groups. In the cytosol fraction, however, metallothionein (MT) was significantly decreased in the Cu-NTA-treated mice. Excretion of Cu from liver to bile and blood was not changed in the two groups. The poor induction of MT by Cu-NTA supports the possibility that the compound is more harmful than CuSO4.

Animals↗
PubMed1989

Testicular dysfunction induced by cadmium and its improvement caused by selenium in the mouse.

Histological observation revealed widespread and severe necrosis at 3 days after the final injection of Cd (0.012 mmol/Kg. daily for 2 consecutive days). Two months later, the changes were further aggravated. In addition, severe atrophy was found, and there was an increase in materials which could be stained by the Kossa method. These changes were prevented by the simultaneous injection of Se (0.024 mmol/Kg, daily for 2 consecutive days). Two months later, the Cd group showed no longer its reproduction. As a result of the Cd injection, at 3 days lipoperoxide concentration, expressed as substances reacting with thiobarbituric acid, was increased significantly, and accompanied by a decrease of glutathione. The levels of lipoperoxide and glutathione values were restored to the control level by the Se injection. At 3 days, testicular Zn and Mg decreased significantly, but Ca and Fe increased markedly in the Cd group. Ca increased mainly in the slow-speed centrifugation fraction, while Mg decreased evenly. In the Cd + Se group, there was no detectable change of metal concentration. However, Se stimulated the Cd uptake into the testis and vice versa. The testicular Cd and Se contents were maintained at a constant level for 2 months. The proportions of Cd existing in the cytosol fraction were 80% and 45% in the Cd group and the Cd + Se group, respectively. Furthermore, the recovery rates for cytosolic Cd in the F2 fractions corresponding to metallothionein were 60% and 75% in the Cd and Cd + Se groups, respectively. Our results suggest that Se has multiple functions against testicular Cd toxicity and that the toxicity once blocked by Se does not occur for a relatively long time.

Animals↗
PubMed1988

Decrease of serum triglyceride in normal rats fed with 2000 ppm aluminum diet for 67 days. I. Feeding young rats sucrose, lactose, milk, casein or soy-protein diets with addition of aluminum chloride.

Aluminum (Al) compounds are widely used in drugs and food additives but the toxicity of such compounds is not known in detail except in patients with renal insufficiency (J. W. Coburn and A. C. Alfrey, 1986, Kidney Int. 29, Suppl. 18). In this experiment, toxicity of ingested Al was investigated in relation to nutritional conditions in normal rats having no renal insufficiency. Sucrose, lactose, milk, casein and soy-protein diets were prepared. As the Al source, aluminum chloride (AlCl3) was added to these diets at the level of 2000 micrograms/g (ppm). Male weanling Wistar rats were fed for 67 days without any Al effect on body weight gain. After a half-day starvation they were terminated. The significance of difference resulting from Al treatment was statistically tested between rats consuming diet with or without added Al. Serum Al concentrations did not exceed 20 ng/ml in any of the groups. Tibia Al concentration doubled in rats consuming added Al in every diet but lactose. Liver Al concentration increased significantly in the Sucrose, Milk, and Casein groups compared to each Control group consuming diet without addition of Al. No lactose effect on Al accumulation was observed. With Al treatment, anemia and hypophosphatemia were not observed, but a decrease in tibia weight was observed with every diet. Aluminum-dependent decreases in serum triglyceride (TG) concentration were also observed in all dietary groups, without any effect on serum cholesterol or phospholipid (P-lipid) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1988

Decrease of serum triglyceride in normal rat fed with 2000 ppm aluminum diet for 67 days. II. Feeding young and adult rats a sucrose diet with addition of aluminum hydroxide and aluminum potassium sulfate.

To confirm the hypotriglyceridemic effect of aluminum (Al), male weanling and adult Wistar rats were fed sucrose diets with the addition of aluminum hydroxide (Al(OH)3) or aluminum potassium sulfate (AlK(SO4)2) for 67 days. As in the foregoing report (C. Sugawara, N. Sugawara, H. Kiyosawa, and H. Miyake, Fundam. Appl. Toxicol. 10, 607-615), no Al-induced anemia or hypophosphatemia was observed and serum Al did not exceed 20 ng/ml. Serum triglyceride (TG) was decreased by aluminum. Serum TG was significantly correlated with the serum nonesterified fatty acid (NEFA) concentration in both the Young groups (R = 0.757, n = 22, p less than 0.01) and the Adult groups (R = 0.727, n = 19, p less than 0.01). Neither serum cholesterol nor phospholipids was affected by Al ingestion. Aluminum caused a decrease in hepatic glycogen in all groups, but the decrease was significant only in Adult groups. Glycerol tri[9,10(n)-3H]oleate was administered by gastric tube into rats fed for 81 days with experimental diets. In all the Al-treated groups serum 3H was significantly greater than in control groups at 3 hr after intubation. At 24 hr after intubation, serum 3H did not differ between Control and Al-treated groups. Total 3H at 24 hr found in serum, liver, and epididymal adipose tissue was not changed significantly by Al feeding. These effects were observed without measurable increase of Al in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Alum Compounds↗
PubMed1988

Increases of serum phosphorus concentration and duodenal, renal and femur alkaline phosphatase (EC 3.1.3.1) activities of normal rats fed 2000 ppm aluminum diets.

In order to investigate the dietary effect of calcium on aluminum-induced hypophosphatemia, five types of diet, sucrose, lactose, milk, casein and soy protein, were prepared. These diets differed with regard to Ca concentration, and carbohydrate or protein sources which were expected to modify intestinal Ca absorption. Weanling Wistar rats were fed these diets for 67 days with the addition of Al at a concentration of 2000 ppm. Nutritional constituents had little effect on Al accumulation in the duodenum and bone. Al treatments had no effects on increases of body weight. The Al treatments significantly increased duodenum alkaline phosphatase (ALPase) activity and serum phosphorus concentration in all of the dietary groups. Slight but significant decreases of bone weight were observed. There were no significant increases in serum Al concentration but bone and kidney ALPase activities were also observed. These results suggest that Al ingestion can cause hyperphosphatemia in the intact animal. Effects of Al on nutrition should be considered even if serum Al concentration does not increase.

Alkaline Phosphatase↗