The induction of hepatic microsomal UDP-glucuronosyltransferase by the methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats.
The effects of nine methylsulfonyl (MeSO(2)) metabolites of tetra-, penta- and hexachlorinated biphenyls (tetra-, penta- and hexaCBs; 20 micromol/kg once daily for 4 days) on the hepatic microsomal UDP-glucuronosyltransferase (UDP-GT) were investigated in male Sprague-Dawley rats. Each of the seven 3-MeSO(2)-PCBs, 3-MeSO(2)-2, 2',4',5-tetraCB (3-MeSO(2)-CB49), 3-MeSO(2)-2,3',4',5-tetraCB (3-MeSO(2)-CB70), 3-MeSO(2)-2,2',3',4',5-pentaCB (3-MeSO(2)-CB87), 3-MeSO(2)-2,2',4',5,5'-pentaCB (3-MeSO(2)-CB101), 3-MeSO(2)-2,2',3', 4',5,6-hexaCB (3-MeSO(2)-CB132), 3-MeSO(2)-2,2',3',4',5,5'-hexaCB (3-MeSO(2)-CB141), 3-MeSO(2)-2,2',4',5,5',6-hexaCB (3-MeSO(2)-CB149) and 4-MeSO(2)-2,2',4',5,5'-pentaCB (4-MeSO(2)-CB101) increased the activities of UDP-GT toward chloramphenicol, 4-nitrophenol and 4-methylumbelliferone. 4-MeSO(2)-2,2',4',5,5',6-hexaCB (4-MeSO(2)-CB149) increased the activity of UDP-GT toward chloramphenicol (UGT2B1) but not toward 4-nitrophenol (UGT1A6) and 4-methylumbelliferone (UGT1A6). The activity of UDP-GT toward thyroxine (T(4)) significantly increased after the administration of each of the seven 3-MeSO(2)-PCBs and 4-MeSO(2)-CB101. Significant correlation was found between the activity of UDP-GT toward T(4) and serum total T(4) concentration after the administration of each of the MeSO(2) derivatives except 4-MeSO(2)-CB149. In conclusion, seven 3-MeSO(2)-PCBs and 4-MeSO(2)-CB101 induce both UGT2B1 and UGT1A6, and 4-MeSO(2)-CB149 induces UGT 2B1. The results from the present study indicate that increase in the hepatic T(4) glucuronidation after the administration of the seven 3-MeSO(2)-PCBs and 4-MeSO(2)-CB101 possibly because of the induction of both UGT1A1 and UGT1A6 caused the reduction of serum T(4) levels.
Kato
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Shizuoka, Japan. kato@ys7.u-shizuoka-ken.ac.jp
Haraguchi
K
K
Shibahara
T
T
Shinmura
Y
Y
Masuda
Y
Y
Kimura
R
R
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011078:Polychlorinated Biphenyls / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000378:metabolism / Q000494:pharmacology*; D013974:Thyroxine / Q000097:blood
D013450:Sulfones; D011078:Polychlorinated Biphenyls; D014453:Glucuronosyltransferase; D013974:Thyroxine