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Biomedical subjects

O Wada

Publications and source records attributed to O Wada.

At least 145 records · Page 8Linked to original sources
PubMed1984

Distribution and chromium-binding capacity of a low-molecular-weight, chromium-binding substance in mice.

The distribution of low-molecular-weight, chromium-binding substance (LMWCr) and high-molecular-weight, chromium-binding substance (HMWCr) in the organ cytosol were analyzed by means of Sephadex G-25 gel filtration, after a single i.p. injection of K2Cr2O7 (280 mumol, Cr/Kg) to mice (male dd, 23 +/- 2 g). The amount of Cr in LMWCr per mouse was highest in the liver (83 micrograms), followed by those in the kidney (10 micrograms) and other organs (3-1 micrograms), with lesser amounts of Cr in HMWCr in all the organs. In these organs LMWCr was found to bind 3-28 times the amount of Cr to that in the in vivo binding after the in vitro incubation with K2Cr2O7 at 37 degrees C, showing a high Cr binding capacity of the substance. No inductive formation of LMWCr was observed in the liver even after daily repetitive administration of Cr (150 mumol/Kg, 4 days). Time course studies on the liver and the kidney of mice injected with K2Cr2O7 showed no difference in the accumulation of Cr in LMWCr and in the ratio of Cr in LMWCr to that in HMWCr between the organs at intervals of from 5 min to 24 hr after the injection. The comparative affinity of Cr(III) for LMWCr and for the serum proteins decreases in the order LMWCr, transferrin, albumin. The transfer of Cr from LMWCr to albumin and vice versa was almost negligible. However, significant amounts of the metal transfer was found from LMWCr to transferrin and vice versa, and from albumin to transferrin. These findings suggest that LMWCr is distributed widely in the body and it quickly binds invaded Cr in stable form at an organ site, especially in the liver, with participation of albumin or/then transferrin. This supports the hypothesis that LMWCr plays a large role in Cr detoxification.

Animals↗
PubMed1984

[Effect of triphenyltin chloride on superoxide (O2-.) production in human neutrophils].

Brief treatment (3 min at 37 degrees C) of human neutrophils with triphenyltin chloride (TPTC1) resulted in a dose-dependent inhibition of superoxide (O2-.) production stimulated by concanavalin A+ cytochalasin D. It was considered from the following findings that the inhibition may be caused by some functional disorders of neutrophils: 1) O2-. generated by xanthine oxidase-acetaldehyde system was not inhibited by TPTC1. 2) There was no change in cell viability after treatment with TPTC1. When the other phenyltin compounds were examined, the relative potencies of inhibitory effect were shown to be in the order of TPTC1 greater than diphenyltin dichloride greater than phenyltin trichloride greater than tetraphenyltin on a molar basis. Lysosomal enzyme release caused by neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was also inhibited by TPTC1. These results suggest that TPTC1 inhibits the common pathway(s) of the two stimulus responses.

Glucuronidase↗
PubMed1983

Triphenyltin chloride inhibits superoxide production by human neutrophils stimulated with a surface active agent.

Treatment of human neutrophils with triphenyltin chloride (TPTCl)-inhibited superoxide (O-2) production stimulated with phorbol myristate acetate (PMA). TPTCl was more potent as inhibitor of O-2 production than other phenyltin compounds. The O-2 production by the xanthine oxidase-acetaldehyde system was not inhibited by TPTCl. This finding indicates that TPTCl does not itself react with O-2. Furthermore, TPTCl did not influence the isolated NADPH oxidase at all, though O-2 production of neutrophils stimulated with PMA in the presence of TPTCl was inhibited. These results indicate that TPTCl inhibits the activation process of the O-2 generating system.

Adult↗
PubMed1983

Triphenyltin fluoride in vitro inhibition of rabbit platelet collagen-induced aggregation and ATP secretion and blockade of arachidonic acid mobilization from membrane phospholipids.

Recent studies have demonstrated that triphenyltin fluoride (TPTF) inhibits collagen-induced aggregation and ATP secretion of rabbit platelets in vivo [S. Manabe and O. Wada, J. Toxic. Sci. 6, 236 (1981)]. The aim of the present investigation was to test the effects in vitro of TPTF on platelet aggregation and to elucidate the mechanism of the inhibitory action by studying the release and metabolism of arachidonic acid and the cyclic AMP contents of rabbit platelets treated in vitro with TPTF. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited both reactions induced by collagen. Triphenylarsine and triphenylantimony did not inhibit, even at a concentration of 10(-3) M. The anti-aggregating concentration (IC50) of TPTF was 6.0 x 10(-6) M against collagen. TPTF had no inhibitory effect on the conversion of exogenous arachidonic acid to malondialdehyde (MDA) by platelets, while the collagen-induced production of arachidonate metabolites [MDA, 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and thromboxane B2] was remarkably inhibited by TPTF. Furthermore, TPTF apparently inhibited the collagen-induced release of arachidonic acid from platelets, although the formation of phosphatidic acid was not inhibited. Total cyclic AMP content after TPTF exposure was not changed significantly. These results indicate that TPTF inhibited the collagen-induced arachidonic acid release from platelet phospholipids, presumably by acting on phospholipase A2. Furthermore, it seems unlikely that the inhibition of arachidonic acid release by TPTF can be explained by the level of cyclic AMP in platelets.

Adenosine Triphosphate↗
PubMed1983

Inhibition of oxidative metabolism in rabbit polymorphonuclear leukocytes by triphenyltin chloride.

Treatment of rabbit polymorphonuclear leukocytes (PMN) with triphenyltin chloride (TPTCl) inhibited chemiluminescence generation stimulated by particulate stimulus, zymosan, or soluble stimuli, concanavalin A + cytochalasin D. Superoxide anion (O-2) production was also inhibited, indicating that the inhibition involved inhibition of early oxidative metabolic process(es). The direct inhibition of the activation process of the oxidative burst was established by the experiments showing that a) chemiluminescence generated by xanthine oxidase-acetaldehyde system was not inhibited by TPTCl, b) washing the PMN after the treatment with TPTCl did not affect the results of chemiluminescence, and c) there was no change in cell viability after the treatment with TPTCl.

Animals↗
PubMed1983

Purification and chromium-excretory function of low-molecular-weight, chromium-binding substances from dog liver.

From liver of dogs injected iv with potassium dichromate (38 mg/kg body wt), a low-molecular-weight chromium-binding substance (LMCr) was purified into two subfractions, LMCr I and LMCr II, which differ in physical and chemical properties. LMCr I was identified to be an anionic, organic chromium compound with a molecular weight of 1500. It contained glutamic acid, glycine, and cysteine as the predominant amino acids and firmly bound chromium in a ratio of one chromium(III) to one molecule of LMCr I. LMCr II was isolated in crystalline form and demonstrated to be a water-soluble, inorganic chromium(III) complex consisting of Na2HPO4 . 7H2O and Na2HPO4 . 2H2O. Although its crystallization reduced the chromium content, it had a maximum chromium-binding capacity as much as one chromium per one phosphorus in water. The mixture of LMCr I and LMCr II as approximated to be the natural composition showed a lower acute toxicity as measured by lethality in mice and had higher rates of urinary excretion and renal clearance in rabbits, accompanied by lower rates of renal tubular reabsorption and retention in kidney and liver than potassium dichromate(VI) and chromium(III) chloride. Pretreatment with chromium-free LMCr II remarkably reduced the mortality rates of mice acutely poisoned with chromium chloride. These results indicate that LMCr plays an important role in the detoxification and excretion of chromium in mammals.

Amino Acids↗
PubMed1983

Role of brain lysosomes in the development of manganese toxicity in mice.

To study the mechanism of development of manganese toxicity, the manganese content in blood, brain, liver, and subcellular fractions of brain was measured at several intervals following ip injection of a single dose of manganese (245 mg Mn(CH3COO)2 X 4H2O/kg body wt) in mice. The ultrastructural alterations in neurons were correlated with the data for manganese content. Peak concentrations of manganese in blood and liver occurred and disappeared in less than 24 hr. In brain, however, manganese concentration was maintained for 4 days and decreased very little during the 10-day postdose interval studied. Most of the absorbed manganese in brain was recovered in mitochondria and lysosome-rich fractions separated by density gradient centrifugation. Lysosomes took up manganese to a greater extent than mitochondria when compared to controls. Electron microscopy revealed that by 24-hr postdose the number of lysosomes in neurons increased in corpus striatum and midbrain in mice given manganese by ip injection. These results suggested that brain lysosomes play an important role in the cellular metabolism of manganese and in the development of manganese toxicity.

Acid Phosphatase↗
PubMed1983

[Effects of tricyclohexyltin hydroxide on carbohydrate and lipid metabolisms].

Male Japan white rabbits were given orally with two doses of tricyclohexyltin hydroxide (TCHT, 250 mg/kg body weight) at 48 hr intervals and their carbohydrate and lipid metabolisms were investigated 48 hr after the last administration. Elevated fasting blood glucose levels and a significant inhibition of insulin (IRI, immunoreactive insulin) release in response to the intravenous glucose infusion were observed. Microscopic examination of pancreatic islets did not reveal any histological alteration. Plasma triglyceride levels were elevated in the TCHT-treated rabbits. Ultracentrifugation of plasma lipoproteins revealed a marked increase in chylomicron + VLDL (very low density lipoprotein) fraction. Rates of triglyceride secretion into plasma were not different between the TCHT-treated and the control animals. These data suggest that TCHT induces hyperglycemia and hyperlipidemia in rabbits, and the disturbance of metabolism seems to be related to the inhibition of insulin release from the pancreatic islets by TCHT.

Animals↗
PubMed1983

[The effect of triphenyltin fluoride on aggregation, ATP secretion and malondialdehyde formation of rabbit platelets in vitro].

Recent studies have demonstrated that triphenyltin fluoride (TPTF), widely used as an agricultural chemical and a marine antifoulant, inhibits collagen-induced platelet aggregation and ATP secretion in rabbits ex vivo. The aim of the present investigation was to elucidate the mechanism of the inhibitory action of TPTF by investigating platelet malondialdehyde (MDA) formation, aggregation and ATP secretion following the stimulation by various stimuli of rabbit platelets treated in vitro with TPTF, other triphenyl metals and aspirin. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited dose-dependently both platelet aggregation and ATP secretion induced by collagen. The antiaggregating (IC50) concentration of TPTF was 6.0 X 10(-6) M against collagen. In addition, TPTF prevented the collagen-, and thrombin-induced formation of MDA, but had little inhibitory effect on the conversion of exogenous arachidonic acid to MDA in platelets. In contrast, aspirin (10(-3) M) inhibited platelet aggregation, ATP secretion and MDA formation induced by all the stimuli tested. Other triphenyl metals did not any inhibitory effect on collagen-, and sodium arachidonate-induced platelet aggregation and ATP secretion even at a final concentration at 10(-3) M. These results suggest that TPTF has a specific inhibitory effect on platelet aggregation and ATP secretion by acting at some step(s) of platelet membrane between the binding site of collagen and thrombin and the release of arachidonic acid.

Adenosine Triphosphate↗
PubMed1982

Intestinal uptake site, enterohepatic circulation, and excretion of tetra- and trialkyltin compounds in mammals.

The intestinal uptake site, enterohepatic circulation, and excretion into bile, feces, and urine of alkyltins (tetra and trialkyltin) were investigated after oral, sc, or intestinal administration of the compounds to rats and rabbits. Assays of tetra- and trialkyltins in biological materials were carried out by gas chromatography. The main uptake sites in the small intestine were the jejunum and duodenum for tetraalkyltins and the ileum and jejunum for trialkyltins. Tetra- and trialkyltins were detected in the small intestine and contents of the intestinal lumen after sc injection of these compounds in rats. These facts suggest that tetra- and trialkyltins are transported in the body through enterohepatic circulation. The route, rate, and amount of excretion of tetra and trialkyltins seem to depend on the velocity of dealkylation, doses, physical and chemical properties, and route of administration of the compounds.

Administration, Oral↗
PubMed1982

Effect of acute administration of cadmium on distribution of zinc in the hamster.

Acute administration of sc doses of Cd (1mg/kg . d, 3 or 6 d) to male golden hamsters resulted in a remarkable dose-dependent increase of Zn in the liver and kidney. In contrast, Zn contents in the heart and testes showed a significant dose-dependent decrease. No change was found in Zn contents of the bone. The correlation coefficients between contents of Cd and Zn in the liver and kidney were much higher in metallothionein fractions than in the corresponding whole organs. These results suggest that Cd induces the synthesis of metallothionein in the liver and kidney, leading to simultaneous accumulation of Cd and Zn in the organs; this in turn decreases the Zn contents in other organs, where weak or no induction of metallothionein synthesis takes place. Therefore Cd might induce Zn deficiency in humans or animals whose pool size and intake of Zn are marginal.

Animals↗