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Biomedical subjects

C Sugawara

Publications and source records attributed to C Sugawara.

At least 55 records · Page 3Linked to original sources

Relationship between ceruloplasmin and Cu status involving metallothionein induced by several heavy metals in the mouse.

ICR male mice aged 5 weeks were injected subcutaneously with CdCl2, Pb(CH3COO)2, AgNO3, CuCl2, a combination of Cd and Ag compounds, or a combination of Cu and Ag compounds. These injections were carried out 3 times. Twenty-four hours after the last injection, they were sacrificed. Cd injection significantly stimulated serum ceruloplasmin (Cp) activity and Cu concentration, accompanied by an increase in hepatic Cu. Pb injection also slightly increased the Cp level. In contrast, Ag injection markedly decreased both Cp activity and Cu concentration in the serum. Hepatic Cu increased slightly after Ag injection. Using a combination of Cd and Ag, only the Ag effect on the Cp activity appeared. The Cu injection stimulated Cu binding to metallothionein (MT) and bile excretion of Cu, but not Cp release. With a Cu and Ag combination, the effect of Ag on Cp was lost, with a concomitant disappearance of Ag from the Cp fraction in the serum. Our results suggest that in the mouse, Cd and Ag, Cu antagonistic metals, influence different sites of Cp metabolism. Excess hepatic Cu is partly eliminated by excretion of bile and is partly detoxified by MT induction.

Animals↗

Effects of ingested 4000ppm aluminum on the essential metals, especially zinc, in intact and ethanol treated mice.

The effects of ingested Al on the essential metals were investigated using mice. Animals were divided into 4 groups: 1) Control, 2) Al, 3) EtOH and 4) Al+EtOH groups. Powdered commercial food, containing 1.26% P, 1.36% Ca, 70ppm Zn, 15ppm Cu, 200ppm Fe and 3.1ppm Al, was used to prepare the diets. For Al-treated groups, Al(AlCl3) was added to powdered food at a concentration of 4000ppm. The co-existing effect of EtOH which is known to affect the essential metals, was also investigated as a possible modulater of Al toxicity at a concentration of 5% for 22 days, followed by 10% for 36 days in the drinking water. After 58 days feeding with food containing Al and / or EtOH containing water, the Al effects on serum and femur P and Ca were found to be slight except for a significant decrease of serum P concentration in the Al+EtOH group. In this group, femur weight was less and femur Al concentration was more compared with the Al group. The effects on Fe and Cu were little. We observed a significant decrease of serum Zn concentration with 4000ppm Al diet in both the Al-treated groups. The fact that serum ALPase activity, a Zn enzyme, increased in disregard of a significant decrease of serum Zn concentration suggested the enzyme release from injures tissues. It is noticeable that a significant decrease of serum Zn concentration was observed when dietary Zn was sufficient. It is reported that the dietary intake of Zn is under the recommended allowance for many people. Since Al compounds are widely used as drugs, food additives and a conditioned latent Zn deficiency is rather common in human diseases, the effects of Al on the Zn metabolism are to be investigated further.

Aluminum↗

Effects of subcutaneous and oral cadmium on iron metabolism: role of ceruloplasmin and metallothionein.

Male ICR mice were either given water containing Cd at a level of 192-200 ppm for 45 days (ingestion group), or were injected subcutaneously once a week with Cd (1 mg/kg) as CdCl2 for 7 weeks (injection group). The control group was given Cd-free water. In both Cd groups, the hematocrit and hemoglobin values did not change markedly. In the ingestion group, the Fe concentration decreased greatly in the liver, kidney, spleen, and duodenum. These decreases may be due to depression of Fe absorption from the intestine. In the injection group, Fe increased in the liver, spleen, and duodenum, although it decreased in the kidney. By Sephadex G-200 gel filtration, Fe-proteins in the hepatic supernatants were located in the void volume region of this gel column in both Cd groups. Apparently, Fe was not a component of metallothionein (MT) protein. The hepatic MT induction by Cd resulted in an increase in hepatic supernatant Cu. Serum Cu and ceruloplasmin (Cp) activity were stimulated only in the injection group. The enhancement of Cp activity may possibly be due to the increase in hepatic Cu which was accompanied by an increase in hepatic Fe, rather than a decrease. Our observations suggest that Fe metabolism is influenced differentially by the administration route of Cd.

Administration, Oral↗

Comparative study of effect of acute administration of cadmium and silver on ceruloplasmin and metallothionein: involvement of disposition of copper, iron, and zinc.

Male ICR mice were subcutaneously injected with either aqueous Ag (1.5 or 5.0 mg/kg) or Cd (1.5 or 2.5 mg/kg) for 2 consecutive days. Body fluids and livers were collected 24 hr after the second dose. In the hepatic supernatant, Ag and Cd were recovered at 2 and 36-46% of the total dose, respectively. Ag-metallothionein (MT), which is associated with Ag, Cu, and Zn, and Cd-MT, which is associated with Cd, Cu, and Zn, were induced in the liver by the injection of Ag and Cd, respectively. The supernatant Ag and Cd existed in the MT fraction at 34-61 and 97% levels, respectively. Cu concentration in the hepatic supernatant was increased by the Ag and Cd injections. The increased Cu was due to the appearance of Ag-MT and Cd-MT, respectively. Microsomal concentrations of Cu increased in the Cd groups, but decreased in the Ag groups. Serum ceruloplasmin (Cp) activity was remarkably increased by the injection of Cd, but severely decreased by the injection of Ag. These opposing changes in Cp activity induced by Cd and Ag may be due not to the sequestering of Cu in MT, but to the alteration of microsomal Cu concentration and/or the difference in affinity of the induction metals to MT. Hepatic Fe concentration was increased by the Ag injection, but was decreased by the Cd injection. These changes may not be related to induction of MT, but to Cp synthesis in the liver.

Animals↗

Effect of silver on ceruloplasmin synthesis in relation to low-molecular-weight protein.

Male mice received a single subcutaneous injection of 10 mg/kg body weight of Ag as AgNO3 and were killed at 2, 6, 10 and 24 h after the injection. Serum ceruloplasmin (Cp) significantly decreased at all times. These low Cp values were accompanied by low serum Cu levels. There was a significant (P less than 0.01) positive correlation between the two substances. A significant enhancement of hepatic Cu concentration was due to the appearance of low Mr protein induced by the Ag administration. The LMW protein induced by Ag was associated with three metals (Ag, Zn and Cu), the Mr values of which ranged from 8300-10 300. In the hepatic supernatant fraction, Ag was recovered at 0.9, 2.7, 9.4 and 8.7% of the doses at 2, 6, 10 and 24 h, respectively. Unexpectedly, the proportion of Ag existing in the low-Mr protein was only 65% of total supernatant Ag, even at 24 h. The decrease in Cp activity with a concomitant increase in hepatic Cu suggests that the increased hepatic Cu was not utilized for the addition to apo-Cp.

Animals↗

Effect of skim milk and yogurt on serum lipids and development of sudanophilic lesions in cholesterol-fed rabbits.

Three groups of male Japanese rabbits weighing about 2.7 kg each were given experimental diets consisting of high cholesterol food and fluid skim milk, yogurt, or water, and were bled every 4 wk to measure serum lipids. After 12 wk they were killed and concentrations of total cholesterol and atheromatous areas dyed with Oil Red O were determined in the aorta to evaluate the development of atherosclerosis. At 8 and 12 wk, the skim milk group showed significantly lower levels of serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride than the control group. Although no significant difference between the yogurt and control groups in the concentration of serum lipids was observed, total cholesterol concentrations in the aorta were significantly lower in both the skim milk and the yogurt groups than in the control group. The atheromatous areas of the skim milk group (38 +/- 34%) were significantly smaller than those of the control group (75 +/- 25%). Significant difference, however, was not found between the yogurt group (51 +/- 22%) and the control group. Concentrations of total cholesterol in the liver did not differ among the three groups. These results suggest that skim milk may have a preventive effect on the development of atherosclerosis.

Animals↗

Selenium protection against testicular lipid peroxidation from cadmium.

Both atrophy and hemorrhage were observed in the testis exposed to two acute subcutaneous injections of Cd (0.012 mmol/kg). The hemorrhage was accompanied by the enhancement of lipoperoxide concentration in the testis. These changes were prevented by the simultaneous injection of 0.024 mmol/kg of Se as SeO2, and testicular Zn, Fe, and glutathione levels recovered to the control level. Se stimulated the uptake of Cd to the testis. Se itself did not show any influence on the level of Zn, Fe, and glutathione. Our observations suggest that the preventive effect of Se is an inactivation of Cd in the testis and that testicular Cd concentration alone cannot be used to assess lipid peroxidation. The compounds linked to the glutathione system or related to the membrane integrity may contribute to peroxidation.

Animals↗

Effect of acute stresses on Zn-thionein production in rat liver.

Male Wistar strain rats were exposed to acute stress from broad-band noise [100 dB (A) for 1 h] or cold (4 degrees C for 24 h). Following exposure to noise for 1 h, serum and adrenal gland showed about 1.8 times and 2.5 times the corticosterone levels of the control group, but this enhancement was not observed after exposure to cole. Both stresses increased Zn-thionein significantly in the liver. Furthermore, the two stresses increased the content of Zn in the 30,000 g supernatant fraction of the liver, though serum Zn concentration was not altered. It is believed that thionein is a regulatory protein with a specific function for Zn metabolism in organs. Although it is known that corticosterone affects Zn metabolism in man and animals, there is little investigation of the effect of environmental stresses on Zn metabolism. The present data suggest that Zn metabolism may be important in the investigation of the effects of repeated and long term exposure to environmental stresses involving noise and cold.

Acute Disease↗

Decrease and recovery of serum zinc and bone growth of rats with chronic ingestion of 25 ppm and 50 ppm cadmium.

Weanling female Wistar rats ingested 25 ppm or 50 ppm cadmium (Cd) as CdCl2 in water for 330 days. Suppression of body weight gain was observed during the early stages of ingestion. The serum zinc (Zn) concentration from Cd-treated rats was significantly decreased in both groups at 35 days. Cd groups gradually exceeded the control group in body weight gain. At the 330th day of Cd ingestion decreased Zn concentration was observed in the fibula bone, though exchangable serum Zn had almost returned to normal. The decrease of calcium (Ca) and hydroxyproline in fibulae was small. The severe decrease in serum Zn concentration during growing stages did not have a suppressing effect on bone growth. The recovery of body weight gain could be partly explained by the smaller intake of Cd water in adults than in young.

Animals↗

Decrease of plasma vitamin A, albumin and zinc in cadmium-treated rats.

Male rats of the Wistar strain were injected subcutaneously with a total dose of 4.5 mg cadmium (Cd) per kg body weight. The first groups (Sc-1) was injected with 18 doses of 0.25 mg/kg, the second group (Sc-II) was injected with 9 doses of 0.50 mg/kg, and the third group (Sc-III) with 2 doses of 2.25 mg/kg. Another group was given water containing 75 ppm Cd for 68 days and 50 ppm for the ensuing 75 days. The plasma concentration of vitamin A (VA) was statistically decreased by the subcutaneous injections of Cd, but the liver concentration of VA was not altered. The fractionated injection of the total Cd apparently reduced the toxicity of Cd on VA metabolism. The decrease of plasma albumin was highly correlated with the decrease of plasma VA. The relative coefficient between them was calculated as 0.812 (n = 34, P less than 0.01) with all of the groups. the relative coefficient between plasma VA and zinc (Zn) was lower than that between plasma VA and albumin but was statistically significant (r = 0.697, P less than 0.01). These results may indicate the involvement of hepatic damage in Cd intoxications. The decrease of plasma VA, however, could not be explained by the Zn deficiency of the liver. To clarify the role of Zn in VA metabolism, the secretion mechanisms of them should be investigated in the liver.

Animals↗

The effect of cadmium on soluble proteins, enzymes, and essential metals of the duodenal mucosa.

In this study, it was observed that Cd administration had effects on metal distribution and enzyme activities and induced metallothionein in the soluble fraction of the duodenal mucosa. Wistar rats were given water containing 100 ppm of Cd ad libitum for 30 days. Cd treatment caused a significant increase in the mucosal weight and in the soluble protein. The existence of metallothionein was apparent and 40% of the soluble Cd was bound to the thionein. Most of the remaining Cd was bound to the larger proteins. The activities of isocitrate dehydrogenase (ICDH) and glucose-6-phosphate dehydrogenase (G6PDH) enzymes, localized in the soluble fraction, were significantly increased by Cd ingestion. The increase of Zn and the decrease of Mn and Mg were also observed in the soluble fraction of the duodenal mucosa.

Adenosine Triphosphatases↗