Kimura R, Sano H, Itagaki K, Kogure T, Sato M, Murata T
J Pharmacobiodyn. 1984 Apr;7(4):234-45. doi: 10.1248/bpb1978.7.234.
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 what different from that of methyl sulfoxides and methyl sulfones.
采用气相色谱 - 质谱联用技术鉴定了间二氯苯（m - DCB）的含硫代谢产物，并对这些代谢产物的处置情况进行了研究。在给大鼠投喂m - DCB后，在其血液、尿液和粪便中出现了2,4 - 和3,5 - 二氯苯基甲基亚砜以及3,5 - 和2,4 - 二氯苯基甲基砜，而它们可能的前体物质，即3,5 - 和2,4 - 二氯苯基甲基硫醚（分别为Me' 和Mf'），在血液、尿液和粪便中未被检测到。然而，在对碱化后的尿液和粪便进行加热后，甲基硫醚出现了。在120小时内，尿液和粪便中排泄的甲基亚砜和甲基砜的累积量均小于给药剂量的0.3%，而Me' 和Mf' 的排泄量分别约为0.9%和0.2%。尿液中排泄的2,4 - 和3,5 - 二氯苯基巯基尿酸的量分别为2.3%和1.2%。然而，在对酸化后的尿液进行加热后，前者增加到27.3%，后者增加到4.3%。未检测到半胱氨酸结合物。投喂m - DCB会降低禁食大鼠肝脏中的谷胱甘肽水平，但预先用马来酸二乙酯（DEM）处理并不会使其进一步降低。投喂m - DCB不会改变肾脏中的谷胱甘肽水平。在预先用DEM处理的大鼠中，甲基亚砜和甲基砜的血液水平及其在尿液中的排泄量显著降低，而预先用DEM处理的大鼠经酸处理尿液中的巯基尿酸并未显著降低。这些结果表明，甲基亚砜和甲基砜源自肝脏中的谷胱甘肽，并且巯基尿酸的形成过程与甲基亚砜和甲基砜的形成过程有所不同。
