Effect of dietary clofibrate on epoxide hydrolase activity in tissues of mice.
The effects of dietary clofibrate on the epoxide-metabolizing enzymes of mouse liver, kidney, lung and testis were evaluated using trans-stilbene oxide as a selective substrate for the cytosolic epoxide hydrolase, cis-stilbene oxide and benzo[a]pyrene 4,5-oxide as substrates for the microsomal form, and cis-stilbene oxide as a substrate for glutathione S-transferase activity. The hydration of trans-stilbene oxide was greatest in liver followed by kidney greater than lung greater than testis. Its hydrolysis was increased significantly in the cytosolic fraction of liver and kidney of clofibrate-treated mice and in the microsomes from the liver. Isoelectric focusing indicates that the same enzyme is responsible for hydrolysis of trans-stilbene oxide in normal and induced liver and kidney. Clofibrate induced glutathione S-transferase activity on cis-stilbene oxide only in the liver. Hydrolysis of both cis-stilbene oxide and benzo[a]pyrene 4,5-oxide was highest in testis followed by liver greater than lung greater than kidney. Hydration of cis-stilbene oxide was induced significantly in both liver and kidney by clofibrate but that of benzo[a]pyrene 4,5-oxide was induced only in the liver. These and other data based on ratios of hydration of benzo[a]pyrene 4,5-oxide to cis-stilbene oxide in tissues of normal and induced animals indicate that there are one or more novel epoxide hydrolase activities which cannot be accounted for by either the classical cytosolic or microsomal hydrolases. These effects are notable in the microsomes of kidney and especially in the cytosol of testis.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism; D002994:Clofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004851:Epoxide Hydrolases / Q000032:analysis*; D005982:Glutathione Transferase / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008830:Microbodies / Q000187:drug effects; D013267:Stilbenes / Q000378:metabolism
D001580:Benzopyrenes; D013267:Stilbenes; C006707:benzo(a)pyrene 4,5-epoxide; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D002994:Clofibrate; C025906:stilbene oxide