IDENTIFICATION OF SULFUR-CONTAINING METABILITES OF m-DICHLOROBENZENE AND THEIR DISPOSITION AND RELATIONSHIP WITH GLUTATHIONE IN RATS

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概要

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• The sulfur-containing metabolites of m-dichlorobenzene (m-DCB) were identified by using gas chromatography-mass spectrometry and disposition of these metabolites was studied. In the blood, urine and feces of rats dosed with m-DCB, 2,4-and 3,5-dichlorophenyl methyl sulfoxides and 3,5-and 2,4-dichlorophenyl methyl sulfones emerged, while their possible precursors, 3,5-and 2,4-dichlorophenyl methyl sulfides (Me' and Mf', respectively), were not detected in the blood, urine and feces. However, after heating the alkalinized urine and feces, the methyl sulfides appeared. Each cumulative amount of the methyl sulfoxides and methyl sulfones excreted in both the urine and feces for 120 h was less than 0.3% of the dose, while the amounts of Me' and Mf' excreted were about 0.9 and 0.2%, respectively. The amounts of 2,4-and 3,5-dichlorophenyl mercapturic acids excreted in the urine were 2.3 and 1.2%, respectively. However, the former was increased to 27.3% and the latter to 4.3% after heating the acidified urine. The cystein conjugates were not detected. The administration of m-DCB decreased the glutathione level in liver of fasted rats but it was not further reduced by diethyl maleate (DEM)-pretreatment. The kidney glutathione level was not altered by the administration of m-DCB. The blood level of methyl sulfoxides and methyl sulfones and their excretion in urine were markedly decreased in DEM-pretreated rats, while the mercapturic acids in acid-treated urine of DEM-pretreated rats were not significantly decreased. These results suggest that the methyl sulfoxides and methyl sulfones were derived from glutathione in liver and the formation process of mercapturic acids was somewhat different from that of methyl sulfoxides and methyl sulfones.

• 公益社団法人日本薬学会の論文

著者

• Sato M

  School Of Pharmaceutical Sciences University Of Shizuoka:(present Address)marusa Corporation

• ITO Keiji

  Hokkaido College of Pharmacy

• MURATA TOSHIRO

  Shizuoka College of Pharmacy

• SATO MASAKI

  Shizuoka College of Pharmacy

• KIMURA RYOHEI

  Shizuoka College of Pharmacy

• SANO HIROSHI

  Shizuoka College of Pharmacy

• ITAGAKI KENJI

  Shizuoka College of Pharmacy

• KOGURE TOSHIHIRO

  Shizuoka College of Pharmacy

• KOGURE Toshihiro

  School of Pharmaceutical Science, University of Shizuoka

• Kimura Ryohei

  School Of Pharmaceutical Sciences University Of Shizuoka

• SATO Masaki

  the Faculty of Science and Engineering, Chuo University

• Sato Masaki

  The Faculty Of Science And Engineering Chuo University

• Ito Keiji

  Department Of Pediatrics Hokkaido Children's Hospital And Medical Center

• Ito Keiji

  Shizuoka College Of Pharmacy

• Kogure Toshihiro

  School Of Pharmaceutical Science University Of Shizuoka

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