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Biomedical subjects

K Haraguchi

Publications and source records attributed to K Haraguchi.

169 records · Page 10Linked to original sources

Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats.

Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO2) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO2-2,2',3',4',5,6-hexachlorobiphenyl (3-MeSO2-CB132); 3-MeSO2-2,2',3',4', 5,5'-hexachlorobiphenyl (3-MeSO2-CB141); 3-MeSO2-2,2',4',5,5',6-hexachlorobiphenyl (3-MeSO2-CB149) and 4-MeSO2-2,2',4',5,5',6-hexachlorobiphenyl (4-MeSO2-CB149). The congeners were major MeSO2-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO2 metabolites (20 micromol/kg once daily for 4 days) reduced serum total thyroxine levels by 22-44% at a much lower dose than phenobarbital (PB; 431 micromol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO2-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO2-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO2-CB132, 3-MeSO2-CB141 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149. Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.

Animals↗

Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-, penta- and hexachlorinated biphenyls in male Sprague-Dawley rats.

Male Sprague-Dawley rats received four consecutive intraperitoneal doses of nine methylsulfonyl (MeSO2) metabolites of tetra-, penta- and hexachlorinated biphenyls (tetra-, penta- and hexaCBs) to determine their effects on thyroid hormone levels. Nine MeSO2 metabolites, major MeSO2-PCBs detected in human milk, liver and adipose tissue, were 3-MeSO2-2,2',4',5-tetraCB (3-MeSO2-CB49), 3-MeSO2-2,3',4',5-tetraCB (3-MeSO2-CB70), 3-MeSO2-2,2',3',4',5-pentaCB (3-MeSO2-CB87), 3-MeSO2-2,2',4',5,5'-pentaCB (3-MeSO2-CB101), 4-MeSO2-2,2',4',5,5'-pentaCB (4-MeSO2-CB101), 3-MeSO2-2,2',3',4',5,6-hexaCB (3-MeSO2-CB132), 3-MeSO2-2,2',3',4',5,5'-hexaCB (3-MeSO2-CB141), 3-MeSO2-2,2',4',5,5',6-hexaCB (3-MeSO2-CB149) and 4-MeSO2-2,2',4',5,5',6-hexaCB (4-MeSO2-CB149). All nine MeSO2 metabolites (20 micromol/kg once daily for four days) reduced serum total thyroxine levels (16-44%) at a much lower dose than phenobarbital (431 micromol/kg once daily for four days) on days 2, 3, 4 and 7 after the last dosage. Total triiodothyronine level was reduced 37% by treatments with 3-MeSO2-CB49 and 3-MeSO2-CB149 at day 7, but increased 35% and 38% by 3-MeSO2-CB70 and 4-MeSO2-CB101 at days 3 and 4, respectively. The reductions in thyroxine levels led to an increase in thyroid-stimulating hormone levels by 3-MeSO2-CB49, 3-MeSO2-CB87, 3-MeSO2-CB101, 3-MeSO2-CB132, 3-MeSO2-CB141, 3-MeSO2-CB149 and 4-MeSO2-CB149. A 30% increase in thyroid weight was produced by 3-MeSO2-CB101 and 3-MeSO2-CB141 treatments. Total cytochrome P450 content and the activity of 7-pentoxyrosorufin O-dealkylase were increased by all seven 3-MeSO2-PCBs. 3-MeSO2-CB49, 3-MeSO2-CB87, 3-MeSO2-CB101 and 3-MeSO2-CB132 also increased the activity of 7-ethoxyresorufin O-dealkylase. Thus, it is likely that all nine tested MeSO2 metabolites could influence thyroid hormone metabolism. The results show that tested 3- and 4-MeSO2 metabolites of tetra-, penta- and hexaCBs reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.

Animals↗

Analytical method for minute amounts of polychlorinated biphenyl methylsulfones from fatty tissue.

Five methylsulfone (MSF) derivatives of polychlorinated biphenyls (PCBs) containing 2 to 6 chlorine atoms were synthesized and fortified in bovine fat. The samples were saponified in sodium hydroxide ethanol solution, extracted with n-hexane after dilution with a double volume of water, and chromatographed on a column of silica gel eluting successively with n-hexane and 5% and 50% diethyl ether in n-hexane. The third eluate was partitioned between n-hexane and concentrated sulfuric acid and back-extracted with n-hexane from 70% sulfuric acid solution. The extract was further partitioned between n-hexane and 90% acetonitrile and back-extracted with n-hexane from 20% acetonitrile solution. The final extract was analyzed by gas chromatography with electron capture detection. Recovery of the MSF-PCBs from the bovine fat by the clean-up procedure was greater than 93% in most cases. The method can determine 5 ng and 100 ng each of the MSF-PCBs in a 5-g fatty sample with ca. 10 and 6% precision, respectively.

Acetonitriles↗

Differential diagnosis between organic and inorganic mercury poisoning in human cases--the pathologic point of view.

Differences in pathology were found between acute and chronic exposure to methylmercury, mercury vapor, and inorganic mercury. Characteristic pathologic changes produced by organic mercury in the brain have previously been described in patients with Minamata disease. The brains of patients who presented with acute onset of symptoms and died within 2-mo showed loss of neurons with reactive proliferation of glial cells, microcavitation, vascular congestion, petechial hemorrhage, and edema in the cerebral cortices, predominantly in the calcarine, pre- and postcentral, and transverse temporal cortices and in the cerebellar cortex. The neuropathologic changes in the patients with acute onset of symptoms who survived for a long period (>10 yr) were also included neuronal loss with reactive proliferation of glial cells in similar anatomic locations. The neuropathologic changes in patients with inorganic mercury poisoning are quite different. Autopsies performed on 3 individuals with fatal cases of acute inorganic mercury poisoning who were exposed to mercury vapor for about 2 wk revealed diffuse organized pneumonia, renal cortical necrosis, disseminated intravascular coagulopathy, and infarctions in the brain and kidneys. In 2 other patients who worked in mercury mines for about 10 yr and who suffered from chronic inorganic poisoning, no specific lesions were demonstrated in the brain. However, the assay and the histochemistry of mercury revealed that inorganic mercury was present in the brain in all 3 groups irrespective of the brain lesions and the duration of clinical signs.

Adult↗