Comparison of the potencies of (+)- and (-)-2-ethylhexanoic acid in causing peroxisome proliferation and related biological effects in mouse liver.
Male C57BL/6 mice were exposed to 1% (w/w) (+)- or (-)-2-ethylhexanoic acid or an equimolar mixture of these enantiomers in their diet for 4 or 10 days. A significant increase in liver weight and a 2- to 3-fold increase in the protein content of the mitochondrial fraction were seen in all cases. Peroxisomal palmitoyl-CoA oxidation was increased 2- to 3.5-fold after 4 days of treatment and 4- to 5-fold after 10 days, while the corresponding increases in peroxisomal lauroyl-CoA oxidase activity were 2- to 3-fold and 9- to 12-fold, respectively. Peroxisomal catalase activity was unchanged, whereas the microsomal and cytosolic activities were increased 2- to 3-fold and 6- to 16-fold, respectively. These treatments also induced microsomal omega-hydroxylation of lauric acid 7-fold and soluble epoxide hydrolase activity in the mitochondrial and cytosolic fractions, as well as microsomal epoxide hydrolase activity about 50-100%. The only significant differences observed between the effects of (+)-2-ethylhexanoic acid and its (-)-enantiomer were on peroxisomal palmitoyl-CoA oxidation and lauroyl-CoA oxidase activity after 4 days of treatment. In both these cases the (+)-enantiomer resulted in increases which were 50-75% greater than those seen with the (-)-form.
Sundberg
C
C
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Wachtmeister
C A
CA
Lundgren
B
B
DePierre
J W
JW
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002208:Caproates / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008830:Microbodies / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D002208:Caproates; C040668:2-ethylhexanoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D002374:Catalase; D042926:Cytochrome P-450 CYP4A; C028427:palmitoyl CoA oxidase; D004851:Epoxide Hydrolases