Effect of microsomal enzyme inducing agents on hepatic biotransformation in cotton rats (Sigmodon hispidus): comparison to that in Sprague-Dawley rats.
1. Activities of several biotransformation enzymes were determined in male and female Sigmodon hispidus. Benzphetamine N-demethylase and glutathione S-transferases toward 1-chloro-2,4-dinitrobenzene and sulfobromophthalein were higher in male Sigmodon hispidus than the female animals. 2. The study also determined the effect of microsomal enzyme inducing agents on hepatic biotransformation in male Sigmodon hispidus. 3. Cytochrome P-450 concentration was similar in cotton and Sprague-Dawley rats, and was increased after phenobarbital, pregnenolone-16 alpha-carbonitrile, or 3-methylcholanthrene treatment. 4. Benzphetamine N-demethylase was 4-fold higher in Sigmodon hispidus and was induced by 75-100% after phenobarbital. 5. UDP-Glucuronosyltransferase toward estrone, 1-naphthol, diethylstilbestrol and testosterone was 2- to 4-fold higher in cotton rats and was not altered by treatment with the inducing agents. 6. Conjugation of 1-chloro-2,4-dinitrobenzene, ethacrynic acid and sulfobromophthalein with glutathione was similar in both rodent species and was not inducible. 7. Sulfation of 2-naphthol was 15-30% of that in Sprague-Dawley rats and was not increased by inducer administration.
Medical Sciences Program, Indiana University School of Medicine, Bloomington 47405.
J B
JB
Watkins
D000818:Animals; D015239:Arylsulfotransferase; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004790:Enzyme Induction; D004976:Ethacrynic Acid / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013448:Sulfobromophthalein / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D004137:Dinitrochlorobenzene; D013448:Sulfobromophthalein; D011285:Pregnenolone Carbonitrile; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; C069947:2-naphthol sulfotransferase; D015238:Sulfotransferases; D015239:Arylsulfotransferase; D004976:Ethacrynic Acid; D010634:Phenobarbital