2,2',3,4,4',5'-六塩素化ビフェニル（CB138）のモルモットにおけるin vivo代謝

Our preceding studies reported using animal liver microsomes that 2, 2', 3, 4, 4', 5'-hexachlorobiphenyl (hexaCB) (CB138), a worldwide and persistent organohalogen pollutant, was metabolized to two major hydroxy (OH)-metabolites, 3'-OH-CB138 (M-3) and 2'-OH-2,3,3',4,4', 5'-hexaCB (M-4), and two dechlorinated OH-metabolites (M-1 and M-2) in guinea pigs at much faster rate than in rats and hamsters. In this study, the distribution of four CB138 metabolites to the serum and liver 4 days after exposure and their fecal excretion were studied in guinea pigs administered with CB138 intraperitoneally. 3'-OH-CB138 (M-3) was a major metabolite in the liver, serum and feces. M-1 was observed as a minor metabolite in guinea pig feces. In contrast, trace amount of M-2 was present in guinea pig serum. However, 2'-OH-2,3,4,3',4',5'-hexaCB (M-4) which was a major metabolite in the in vitro system using guinea pig liver microsomes was not found in all tissues and feces tested in this study. On the other hand, the exact chemical structures of M-1 and M-2 were determined to be 6'-OH-2, 3, 3',4,4'-pentaCB and 4'-OH-2, 2',3,4,5'-pentaCB, respectively, by comparison of the retention time and mass fragmentation of the synthetic authentic amples in GC-MS. From these results, it is suggested that the metabolism of CB138 in guinea pigs may proceed by three pathways, a direct hydroxylation at 3'-position, and also the formation of 2',3'- or 3', 4'-epoxide and subsequent dechlorination and that three metabolites show the different mode of distribution and excretion.特集号 油症とPCB及びダイキシン関連化合物 研究報告 第23集 責任編集者 古江増隆The Twenty-third Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Furue Masutak

2,2ʼ,3,4,4ʼ,5,5ʼ-七塩素化ビフェニル（CB180）の動物肝ミクロゾームによる代謝

The in vitro metabolism of 2,2ʼ,3,4,4ʼ,5,5ʼ-heptachlorobiphenyl (CB180) was examined using liver microsomes of rats, guinea pigs and hamsters. Of liver microsomes from untreated animals, rats and guinea pigs produced one metabolite (M-1) with the activity of 1.2 and 18.1 pmol/hr/mg protein, respectively, but hamsters did not at all. Pretreatment of phenobarbital (PB) resulted in about 32-fold increase in rats, 4-fold increase in guinea pigs and an appearance of M-1 in hamsters (15 pmol/hr/mg protein). In addition, another metabolite (M-2) was formed only by liver microsomes of PB-treated guinea pigs. In contrast, pretreatment of 3-methylcholanthrene showed no metabolite in three animals. By comparison of the GC-MS data of the metabolites with synthesized authentic samples, M-1 and M-2 was determined to be 3ʼ-hydroxy (OH) -CB180 and 4’-OH-2,2ʼ,3,4,5,5ʼ-hexachlorobiphenyl (CB141), respectively. These results suggest that 3ʼ-OH-CB180 is a major metabolite and is formed by PB-inducible cytochrome P450 (CYP2B enzymes) in animals and also guinea pigs possess much higher activity to metabolize CB180 than rats and hamsters.特集号 油症とPCB及びダイキシン関連化合物 研究報告 第25集 責任編集者 古江増隆The Twenty-fifth Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Editor Furue Masutak

ビペリデンによって誘発されるラットの行動変化 ポリグラムを用いた検討

出版社版せん妄の神経生理学的機序を明らかにするために,中枢性抗コリン薬のビペリデン投与におけるラットの行動変化をポリグラムを用いて検討した.Wistar系雄性ラット7匹を使用した.ビペリデン投与により,Hyperactive stateとHypoactive stateが交互に出現することが認められた.時間経過とともにHypoactive stateの持続時間が数十秒と延長する傾向が認められ,投与後90分以降になるとdrowsinessが観察された.BiperidenあるいはSaline投与前の覚醒時は,速い眼球運動と高振幅の筋電図が認められた.ビペリデン投与によって誘発されるラットの行動変化とポリグラム所見は,ヒトせん妄に類似することが明らかになっ

2,2ʼ,3,4ʼ,5,6,6ʼ-七塩素化ビフェニル（CB188）のラットおよび モルモット肝ミクロゾームによる代謝

The metabolism of a 2,4,6-trichloro-substituted PCB, 2,2ʼ,3,4ʼ,5,6,6ʼ-heptachlorobiphenyl (CB188), by rat and guinea pig liver microsomes was compared to that of a 2,4,5-trichloro-substituted PCB, 2,2ʼ,3,4ʼ,5,5ʼ,6-heptachlorobiphenyl (CB187) using liver microsomes of untreated, phenobarbital (PB)-treated and 3-methylcholanthrene (MC)-treated rats and guinea pigs. Two metabolites, M1 and M2, were produced only by liver microsomes of PB-treated rats with rates of 554 and 187 pmol/hr/mg protein, respectively, but no metabolite by liver microsomes of untreated and MCtreated rats. In addition, no metabolite was observed by all kinds of guinea pig liver microsomes used in this study. GC-MS revealed that both M1 and M2 were mono-hydroxylated CB188. Also, the methylated M1 almost completely agreed with a synthesized authentic 3ʼ-methoxy-CB188 in terms of the retention times and mass fragmentation. These results suggest that 3ʼ-OH-CB188 is a major metabolite formed by PB-inducible CYP2B enzymes in rats and that the 2,4,6-trichloro-substituted PCBs are metabolized much more easily than the 2,4,5-trichloro-substituted PCBsはじめに / 実験方法 / 実験結果 / 考