Naoko Koizumi

Relationship of cadmium accumulation to zinc or copper concentration in horse liver and kidney

The concentrations of Cd, Zn, Cu, and metallothionein (MT) in the liver, renal cortex, and renal medulla were determined in 24 male and 15 female younger thoroughbreds (age 27 to 97 months) and two old male horses (age 154 months and 190 months). High correlations were found between Zn and MT in the liver (partial correlation coefficient 0.836), between Cd and MT in the renal cortex (partial correlation coefficient 0.786), and between Cd and Zn in the renal cortex (partial correlation coefficient 0.675), while the correlation between Cd and MT in the liver was low (partial correlation coefficient 0.124). In the renal medulla, high correlations were found between Cd and Zn (partial correlation coefficient -0.631), between Zn and Cu (partial correlation coefficient 0.881), and between Cd and Cu (partial correlation coefficient 0.785). Therefore, in the liver, the MT concentration is the most highly correlated with the Zn concentration and is not correlated with the CD concentration unless artificially exposed to Cd. In the renal cortex, the MT and Cd concentrations are very highly correlated with each other. The Zn concentration is about 20 micrograms/g when the Cd concentration in the renal cortex is the lowest.

Concentrations of Cadmium, Zinc, Copper, Iron, and Metallothionein in Liver and Kidney of Nonhuman Primates

To evaluate the species specificity of Cd accumulation and the relationship of Cd with other essential metals and metallothionein (MT), the concentrations of Cd, Zn, Cu, and Fe in the liver and kidney and the MT concentrations in the soluble fractions of the liver and kidney were determined in Cd-uncontaminated nonhuman primates (11 species, 26 individuals) kept in a zoo and two wild-caught Japanese macaques. The compositions of metal-binding proteins in the soluble fractions were also investigated by high-performance liquid chromatography (HPLC). The hepatic Cd concentration was 0.03–14.0 µg/g and the renal Cd concentration was 0.35–99.0 µg/g, both varying greatly and being higher in nonhuman primates, which were more closely related to man. The hepatic Zn concentration was 24.0–176 µg/g and the renal Zn concentration was 13.5–138 µg/g, showing 7- to 10-fold differences, and a correlation (r=0.558, p<0.01) was found between renal Zn and renal Cd concentrations.It was proved that in the liver, MT is more closely correlated with Zn (r=0.795, p<0.001) than with Cd (r=0.492, p<0.01) and that in the kidney MT is correlated with both Cd (r=0.784, p<0.001) and Zn (r=0.742, p<0.001). HPLC analysis of metals bound to MT-like protein in chimpanzees, de Brazza’s monkeys, and Bolivian squirrel monkeys showed that more than 90% of Cd in both the liver and kidney, approx 40% of Zn in liver and 28–69% of Zn in kidney were bound to MT-like protein. The higher percentage Zn was bound to high-molecular protein.

Metal concentrations in the liver and kidney of aquatic mammals and penguins

We determined the hepatic and renal concentrations of Cd, Pb, Zn, Cu, and Fe in (1) marine mammals (three bottle-nosed dolphins, six California sea lions, and one sea otter), (2) freshwater and brackish-water mammals (one Oriental short-clawed otter and four European river otters), and (3) sea birds (three rock-hopper penguins, two king penguins, three Humboldt penguins, four Macaroni penguins, and four Magellanic penguins), all of which were kept in a zoo and an aquarium in Japan. We investigated the species-specificity of Cd accumulation in these aquatic animals. We also presented the basic data on metal concentrations. The concentrations of Cd in liver and kidney tended to be higher in marine mammals than in freshwater mammals. Many penguins, sea birds, showed high Cd concentrations. These results suggest that the habits of these animal species may be involved in accumulation of Cd. Pb concentrations were below the detection limit or low in both liver and kidney [not detected (ND)=0.132 µg/g and ND=0.183 µg/g, respectively]. The hepatic concentrations of Zn and Cu were high in young animals. In penguins, a positive correlation was found between the Zn and Cd concentrations in the liver and kidney and between the Cu and Cd concentrations in the liver. Individual variation was large in Fe concentration (48–3746 µg/g in the liver and 51–980 µg/g in the kidney).

Studies on transitory laxative effects of sorbitol and maltitol: II: Differences in laxative effects among various foods containing the sweetening agents

Abstract We studied the laxative effect of sweetening agents, hydrogenated glucose syrup (HGS) containing 88–92% maltitol, and sorbitol contained in various foods. The subjects were 89 volunteers (64 males and 25 females). Foods used in the study were tablets, bevarages, chewing gum, jelly, adzuki-bean jelly, chocolate and candies which contained one of the two sweetening agents. The doses of the sweetening agents were 0.4 g/kg for sweets in tablet form and 20 g for the other foods. Approximately 10% of the subjects exhibited diarrhea after taking tablets as a control; approximately 20% did so after taking HGS except for adzuki-bean jelly; and approximately 30% did so after taking sorbitol. There was no significant difference between HGS and the control substance. The incidence of diarrhea tended to be higher with the two sweetening agents only when contained in adzuki-bean jelly. The length of time between the ingestion of test substances and the first onset of diarrheal stool varied widely from less than one hour to 23 hours among individuals. However, adzuki-bean jelly diarrhea was induced within 5 hours in all subjects. Soft stool accounted for 60 – 90% of the macroscopic findings of diarrheal stool. Chief complaints of abdominal symptoms were gurgling, flatus and lower abdominal pain.

Effects of cadmiumin vitro on contractile and relaxant responses of isolated rat aortas

ObjectiveCadmium is known to affect the vascular tone of isolated blood vesselsin vitro and the arterial pressure of ratsin vivo. However, the mechanisms of cadmium actions on the vascular system have not been clarified. To elucidate the actions of cadmium on vascular tonus, effects of cadmium on vasocontractile and vasorelaxant responsesin vitro were investigated using aortic strips isolated from rats.MethodsAortic strips isolated from male Wistar rats were incubated with CdCl2 (10μM) for 24 hr, washed with fresh CdCl2-free medium, and then used for measurement of isometric tension and Western blot analysis of eNOS (endothelial nitric oxide synthase) and iNOS (inducible nitric oxide synthase).ResultsIn the aortas pretreated with cadmiumin vitro, the contractile response to phenylephrine was significantly higher than that in the control aortic strips pretreated with a vehicle. The sodium nitroprusside-induced relaxing response was significantly higher in the aortic strips pretreated with cadmium for 24 hr, compared with that in the control pretreated with a vehicle. The isoproterenol-induced relaxing response was also significantly higher in the cadmium-accumulated aortic strips.In vitro cadmium treatment slightly but not significantly increased the acetylcholine-induced relaxation of the aortic strips. Cadmium treatment induced expression of iNOS and significantly increased expression of eNOS in the aortic strips, while it did not affect expression of β-actin.ConclusionsCadmium treatmentin vitro augmented the α1 adrenoceptor-mediated contractile response, even though eNOS and iNOS were upregulated by cadmium treatment. NO-induced and β-adrenoceptor-mediated relaxing responses were also augmented by cadmium treatment. These results suggest that both vasocontractile and vasorelaxing responses are augmented in cadmium-accumulated aortas.

Diminished Inibitory Action of Ethanol on the Contraction of Gallbladder Isolated from Chronically Ethanol-Fed Guinea Pigs

Ethanol is known to decrease the gallbladder contractility. The purpose of this study was to clarify the mechanism of tolerance to the inhibitory action of ethanol on the gallbladder contractility. Male guinea pigs were fed ethanol (3%) or calorie-matched sucrose in the drinking water for 4 weeks. Then, the gallbladder was isolated, and its isometric tension was measured. The contractile responses to KCl, BAY K8644, histamine, and phorbol 12,13-dibutyrate in the normal medium were not different between the gallbladder strips from ethanol-fed and control guinea pigs. Ethanol at 25 mmol/l in vitro did not affect the contractile responses to KCl and BAY K8644 in the gallbladder strips from both ethanol-fed and control guinea pigs. On the other hand, ethanol at 25 mmol/l in vitro significantly inhibited the contractile responses to histamine and phorbol 12,13-dibutyrate in the gallbladder strips from the control guinea pigs, but it did not affect the contractile response to histamine and significantly augmented that to phorbol 12,13-dibutyrate in the strips from the ethanol-fed guinea pigs. Diphenhydramine, a selective H1 receptor antagonist, abolished the histamine contraction in gallbladder strips from both control and ethanol-fed guinea pigs, while cimetidine, a selective H2 receptor antagonist, did not affect histamine contraction, implying that histamine-induced contraction of guinea pig gallbladders is mediated only by H1 receptors. Verapamil (1 µmol/l) completely inhibited the phorbol 12,13-dibutyrate-induced contraction of the strips from both ethanol-fed and control guinea pigs. The histamine-induced contraction was partly inhibited in the absence of Ca2+ in the medium. In the gallbladder strips from both ethanol-fed and control guinea pigs, ethanol at 25 mmol/ in vitro did not affect the histamine-induced contraction in the absence of extracellular Ca2+. Tolerance to the inhibitory action of ethanol developed selectively on contractile responses to histamine and phorbol 12,13-dibutyrate. Chronic ethanol administration produces tolerance to in vitro gallbladder contractility mediated by the Ca2+ entry through L-type Ca2+ channels linked with protein kinase C activation.

Relationship of metallothionein to cadmium and to zinc in human liver and kidney

We have studied the correlations between Metallothionein(MT) and heavymetals in various species. Human liver and kidney samples were measured for Cd, Zn, and MT concentrations. We found high correlations between Zn and MT in the liver(correlation coefficient 0.884), and between Cd and MT in the renal cortex(correlation coefficient 0.799), while we found low correlations between Cd and MT in the liver(correlation coefficient -0.043). This suggests that the essential metal Zn, which is necessary for growth may be related in humans to Cd accumulation with age through MT.

Itai-itai disease is not associated with polymorphisms of the estrogen receptor α gene

Abstract Itai-itai (or ouch-ouch) disease is a syndrome accompanied by bone mineral disorders, and which may be related to oral cadmium exposure. Itai-itai predominantly affects postmenopausal women with a history of multiple childbirths. Recently, it has been reported that polymorphisms of the estrogen receptor α (ERα) gene are associated with postmenopausal reduction of bone mineral density in Japanese women. However, estrogen receptors have never been studied in itai-itai disease. In this study, we examined the genotypic distributions of PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of the ERα gene in patients with itai-itai disease and compared them with those of control subjects. The RFLPs are represented here as Pp (PvuII) and Xx (XbaI); the capital and small letters signify the absence and presence of restriction sites, respectively. The genotypic distributions of the patient group were: PP, 14.8%; Pp, 55.6%; pp, 29.6%; XX, 7.4%; Xx, 29.6%; and xx, 63.0%. These distributions were similar to those observed for the control groups, hence no pattern of genotypic distribution was observed that could be related to itai-itai disease. We conclude that RFLPs of the ERα gene may not be associated with itai-itai disease.

Dust concentration around the sites of demolition work after the Great Hanshin-Awaji Earthquake

The total dust concentration and the particle size distribution were determined around die sites of demolition associated with the Great Hanshin-Awaji Earthquake, which occurred on January 17, 1995. The total dust concentrations ranged from 0.20 to 0.23 mg/m3, being about 1.2 to 2.2 times that in die non-demolition area, and intermediate particles (2.1-11.0μm) made up a large proportion of the dust. The dust concentrations were not influenced by the weather on the day preceding measurement around the sites of demolition of concrete buildings, whereas the values decreased to about half around die sites of demolition of wooden buildings, nearly the same concentration in the control areas, when it had rained on the previous day. The dust concentrations increased compared with that in an average year but to The degree of die upper limit of die environmental standard (1 hr-value<0.20 mg/m3) . The dust due to the smoke of Mt. Sakurajima in the surrounding areas accounted for a higher proportion of large particles (<11.0>m) than in the earthquake-devastated area. The concentration of respirable dust (<;7.07>m) in a worker engaged in demolition was 4.0 mg/m3, being twice the recommended concentration (2 mg/m3) of the Japan Society for Occupational Health. It was thus considered that workers should use a respiratory protective device.

Studies on transitory laxative effects of sorbitol and maltitol: III: Alterations in serum contents due to laxative effects

Abstract Maltitol or sorbitol was administered in doses of 0.8 g/kg to 20 physically healthy subjects (10 males and 10 females) and 6 diabetic patients (3 males and 3 females). Maltitol and sorbitol caused diarrhea in 75% and 95% of the subjects, respectively. Stool was watery in most of the subjects. The serum concentration of each sweetening agent was as low as approximately 0.3 mg/dl 2 hours after administration. The serum concentrations of Na, K, Cl, BUN, glucose and insulin did not change 2 hours after administration.