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Biomedical subjects

O Wada

Publications and source records attributed to O Wada.

At least 163 records · Page 9Linked to original sources

[Properties and mechanism of hyperlipidemia induced in rabbits by tributyltin fluoride].

Male Japanese white rabbits were given tributyltin fluoride (TBTF) by gastric intubation with a single dose of 100 mg/kg body weight and their lipid and glucose metabolisms were investigated. After administration of TBTF, a reversible, but remarkable increase of lipids in plasma, particularly of triglycerides and total cholesterol, was observed. Ultracentrifugation of plasma lipoproteins revealed a marked increase in chylomicron+VLDL (very low density lipoprotein) fraction. Lipoprotein lipase (LPL) activity in postheparin plasma reduced significantly (p less than 0.02) to the levels of about 50% of the control. Fasting blood glucose level was elevated and a significant inhibition of insulin (IRI) release in response to the intravenous glucose infusion was observed in TBTF treated rabbits, but the level of blood glucose and the degree of inhibition of IRI release were low compared with those of triphenyltin fluoride treated rabbits, in which much greater fasting hyperglycemia was observed. Microscopic examination of pancreas, kidneys and thyroid gland did not reveal histological alterations contributing to the hyperlipidemia. These results suggest that hyperlipidemia induced in rabbits by tributyltin fluoride is due to decreased LPL activity. The decrease in LPL activity seems to be related to the inhibition of insulin release from islets by TBTF.

Animals↗

[Recent progress in the study of analytical methods, toxicity, metabolism and health effects of organotin compounds].

Over the years, a variety of uses has been found of organic tin compounds as fungicides, as stabilizers in plastics and for other industrial uses. The purpose of this article is to summarize and review the results so far obtained as to the analytical method for organotins in biological samples, the toxicity, metabolism, and biochemical and health effects of organotin compounds. 1) Many methods have been developed for analysis of organotin compounds by spectrophotometry, polarography, gas- or liquid-chromatography, etc. These methods, however, are mainly for analysis of organotins in standard solutions or in water, and are not suitable for organotin compounds in biological samples. Recently, we have developed several methods for analysis of various kinds of organotin compounds in biological samples. These methods are able simultaneously to separate and determine trace amounts (at nanogram order) of organotin compounds and their metabolites in the same biological samples. 2) Acute toxicity of organotin compounds which appeared on the literature are summarized. Trialkyl and triaryl compounds seem to be more toxic than the tetra-, di-, or mono-compounds of the same chain length. With an increase in the number of C atoms the toxicity of alkyl compounds decreases. Aryltin compounds are less toxic than alkyltin compounds. 3) Intestinal absorption sites for tetra-alkyltins are jejunum and duodenum, and those for trialkyltins are ileum and jejunum. A considerable amount of orally administered tetra- and trialkyltins of low molecular weights are absorbed, but only very little of the other organotin compounds seems to be absorbed from the gastrointestinal tract. Absorbed organotin compounds rapidly undergo dealkylation by the microsomal mono-oxygenase system dependent on cytochrome P-450 in the liver, brain or other organs, and the compounds and their metabolites distribute to the whole body, ultimately being excreted into urine, bile and faeces. The biological half life of organotin compounds in mammals is usually short, a half of the amount of tributyl- and triphenyl-tins deposited in the body disappearing in several days. A part of organotin compounds excreted into bile is demonstrated to have been absorbed from the intestine and to circulate in the body via enterohepatic circulation. 4) Specific effects of organotin compounds on the biological systems and health include disturbance of the structure and function of the central nervous system (interstitial edema of white matter), inhibited oxidative phosphorylation in mitochondria of cells, atrophy of the thymus and thymus dependent lymphoid tissues resulting in the dysfunction of T cells for immunity, inhibited enzyme activity, lesions in the liver and bile ducts etc., although some specificity is observed among species of animals and organotin compounds. Recently we found that a single oral administration of triphenyltin fluoride to rabbits induces transient diabetes and diabetic lipemia by inhibiting insulin secretion from morphologically normal pancreatic B-cells...

Animals↗

[Pathogenesis of hyperlipidemia and fatty liver of rabbits induced by methyl iodide. Increased synthesis and secretion of triglyceride in the liver].

Male Japanese white rabbits were injected subcutaneously with methyl iodide (57 mg/kg body weight/day) on two successive days and their lipid metabolism was investigated 48 hr after the last injection. The plasma triglyceride levels increased from the preinjection average of 56.1 mg/dl to 246.0 mg/dl on an average, the individual values being greatly variable. Analysis of lipoprotein profile of plasma showed a significant increase of very low density lipoproteins (VLDL). Lipolytic activities in postheparin plasma did not change. However, rates of triglyceride secretion into plasma, measured by Triton WR 1339 injection method, were significantly higher in the animals treated with methyl iodide than in the controls. Histological investigation of the liver showed diffuse fat deposits in the hepatocytes without any destructive and inflammatory changes. The results indicate that hyperlipidemia and fatty liver of rabbits induced by methyl iodide is related to the elevation of triglyceride synthesis and its secretion in the liver.

Animals↗

Simultaneous determination of trialkyltin homologues in biological materials.

Taking advantage of the high sensitivity of an electron capture detector to alkyltin halides, an analytical method has been developed for the simultaneous determination of trialkyltin homologues in biological materials. Trialkyltins were purified as chlorides from tissues by simultaneous extraction with hydrochloric acid and ethyl acetate, replacement of the extraction solution with n-hexane and stepwise elution with n-hexane-ethyl acetate on a silica gel column. Alternatively, gas chromatographic analysis was carried out on 20% DEGS-HG at temperatures from 100 to 120 degrees C. Detection limits reached 1 x 10(-12) g for trialkyltin chlorides. The recoveries of trialkyltins added to various tissues at the 50-pmole level ranged from 97 to 106%. By in vivo studies, it was confirmed that this method is rapid, sensitive and applicable to biomaterials containing more than 1 ng trialkyltins per gram of tissue.

Animals↗

Rapid method for the determination of tetraalkyltin compounds in various kinds of biological material by gas chromatography.

A rapid gas chromatographic method is described for the simultaneous determination of tetraalkyltin compounds in biological materials. Tetraalkyltins were rapidly purified by direct passage through a silica gel column after extraction from the homogenized tissues with n-hexane. Gas chromatographic analysis was alternatively carried out with PEG 20M at temperatures from 50 to 150 degrees C. A hydrogen flame-ionization detector was more sensitive and selective towards tetraalkyltins than an electron-capture detector. Detection limits reached 1 x 10(-8) g for tetraalkyltins. Recoveries of tetraalkyltins added to various tissues at the 85-nmole level ranged from 97 to 104%. In vivo studies indicated that for a sample containing more than 0.1 micrograms of tetraalkyltins per gram of tissue, the proposed method is accurate enough for quantitative analysis.

Animals↗

[Studies on a specific chromium binding substance (a low-molecular-weight chromium binding substance) in urine (author's transl)].

The aim of this study was to identify a specific substance [a Low-Molecular-Weight Chromium binding substance (LMW Cr)] in normal urine and also to clarify the various factors affecting chromium to bind this substance in urine. The results obtained were as follows: 1. Normal human and rat urines contained unsaturated LMW Cr similar to that found in the liver or other organs of rabbits and dogs. The amount of chromium bound in vitro to the unsaturated LMW Cr in normal human urine was 14.81 +/- 1.84 microgram/ml urine when urine was incubated with trivalent chromium for 30 minutes at 37 degrees C. 2. Higher amounts of chromium were bound to LMW Cr in normal urine a 37 degrees C than at 24 degrees C, in acidic state of urine than in alkaline state, and when trivalent chromium was added to the incubation mixture than when hexavalent chromium was added. Chromium contained in LMW Cr was supposed to be trivalent. Furthermore, boiling urine at 100 degrees C for 10 minutes did not reduce the chromium binding capacity of LMW Cr in urine. These results indicate that LMW Cr in urine binds chromium by a chemical reaction. 3. Amounts of chromium bound to LMW Cr in urine obtained 3 hrs after intraperitoneal injection of 200 mumole K2Cr2O7 to a rat were much higher than amounts of chromium bound in vitro to LMW Cr in normal urine during 3 hrs incubation of the urine with K2Cr2O7. This suggests that most of excessively absorbed chromium is excreted into urine after being bound to LMW Cr in organs. 4. Urine from patients with chronic nephritis excreted a part of added chromium bound to high molecular weight fractions corresponding to peaks of UV absorption.

Adult↗

The effect of age on cadmium retention in organs of hamsters.

Age difference of cadmium retention was investigated in hamsters after a short term cadmium exposure. Three types of organs were identified in relation to cadmium retention, i. e., the liver and testes retained an increasing amount of cadmium with increasing age, the kidney and heart showed a gradual decrease in the retention after a transient increase in young ages and the bone showed no retention. These changes seemed to be related to the de novo synthesis of metallothionein in the organ.

Aging↗

Origin of urinary alkaline phosphatase excreted by cadmium-treatment of rabbits.

In order to ascertain the origin of increased alkaline phosphatase in the urine of rabbits with injured proximal tubules, we studied the phosphatase by an isoenzyme examination, an inhibition test and an inactivation test. Male rabbits were daily injected subcutaneously with cadmium chloride at a dose of 1.5 mg Cd/kg/day. After treatment for three weeks, total activity of alkaline phosphatase and its isoenzyme patterns on agar-gel and disc-gel electrophoresis were examined in the liver, kidney cortex, plasma and urine, and compared with those of the control rabbits. Alkaline phosphatase activity in the urine of the cadmium treated rabbit was about eleven times higher than that of the control (p = less than 0.005), while enzyme activity of plasma showed almost no difference between the two groups. The isoenzyme patterns of alkaline phosphatase in both agar-gel and disc-gel electrophoresis showed that the main band of the isoenzymes of alkaline phosphatase obtained from urine of control rabbits migrated faster than that from plasma, liver, or kidney, while the main isoenzyme from urine of the cadmium group was consistent with the rapid migrating isoenzyme obtained from the kidney. Furthermore, in both groups, alkaline phosphatase activity in plasma was inactivated by the treatments of heat and urea, and inhibited by L-homoarginine, while the enzymes of the kidney and urine were not remarkably effected. The findings suggest that the increased urinary excretion of the enzyme after administration of cadmium to rabbits originates from the kidney.

Alkaline Phosphatase↗

Triphenyltin fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic lipemia by inhibiting insulin secretion from morphologically intact rabbit B-cell.

Recent work in our laboratory has shown that oral administration of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia in rabbits. The present experiments were conducted to elucidate the mechanism of TPTF-induced hypertriglyceridemia in rabbits by a combined biochemical and ultrastructural approach. After a single TPTF administration, fasting blood glucose and plasma triglyceride levels increased significantly (P less than 0.02) for about 20 days. On the other hand, both plasma and adipose tissue lipoprotein lipase (LPL) activity was markedly decreased (P less than 0.001) during this period, and triglyceride production rates on day 2 after TPTF administration was significantly decreased (P less than 0.01). Density-gradient ultracentrifugation showed a remarkable accumulation of chylomicron and VLDL in the composition of plasma lipoproteins. Insulin injection to the hypertriglyceridemic rabbits induced a significant recovery of the decreased plasma LPL activity with a concomitant decrease of plasma triglyceride levels, while abeyance of insulin injection resulted in a decrease of LPL activity again. A significant inhibition of insulin release in response to the loading of glucose, glucagon, or arginine was observed in the TPTF rabbits (P less than 0.02). Inhibition of glucagon release was also observed in the arginine-loading test (P less than 0.01). Electron microscopic studies showed small abnormalities in the pancreatic islets of TPTF-treated rabbits. These findings suggest that TPTF inhibits insulin release from rabbit islets, subsequently inducing diabetic lipemia due to the insulin deficiency. Furthermore, it is possible to provide a new animal model for diabetes and diabetic lipemia by administration of TPTF to rabbits.

Animals↗