Effects of trans-sobrerol on drug metabolizing enzymes in the rat.
1. Metabolism of 14C-trans-sobrerol (I) by Sprague-Dawley rat liver microsomes did not result in covalent binding to proteins, lipid peroxidation or cytochrome P-450 destruction. 2. Subacute and chronic treatment of Sprague-Dawley rats with (I) resulted only in an increase in liver cytosolic GSH-S-transferase. 3. Acute treatment of rats with trans-sobrerol or its metabolite, 8-hydroxycarvotanacetone (II) produced considerable GSH depletion, faster in the case of II, in both liver and lung; the original GSH levels were restored within 24 h. No significant increase in lipid peroxidation was found even when GSH was at its lowest level. 4. UDP-glucuronyltransferase and GSH-S-transferase conjugation occurred with trans-sobrerol and some of its metabolites although at low rates.
Lippi
A
A
Istituto di Mutagenesi e Differenziamento, C.N.R. Pisa, Italy.
Gervasi
P G
PG
Bellucci
G
G
Marioni
F
F
Luzzani
F
F
Ventura
P
P
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*
D005965:Glucuronates; D007202:Indicators and Reagents; D013729:Terpenes; C003316:sobrerol; D006899:Mixed Function Oxygenases; D005978:Glutathione