Influence of partial hepatectomy in dogs on trimethadione metabolism and microsomal monooxygenases.
1. The recovery of trimethadione (TMO) metabolism and its association with liver weight and the activity of TMO N-demethylase have been reported in rat following partial (68%) hepatectomy. In the present study, we examined the effect of liver regeneration on hepatic P450 isozymes and TMO metabolism in dog. 2. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO at 2 h after i.v. injection of TMO (4 mg/kg) fell to 80% of that in the preoperative animals by 24 h after hepatectomy. The DMO/TMO ratio gradually recovered from days 7 to 14, and by day 21 after hepatectomy it had increased to about 25%. At 28 days post-hepatectomy the ratio had returned to preoperative levels. 3. The activity of benzphetamine N-demethylase, TMO N-demethylase, p-nitro-anisole O-demethylase and aniline hydroxylase increased 3 days post-hepatectomy, exhibiting levels 4.77, 3.45, 1.51 and 1.91 times greater respectively than that of the preoperative liver in the same animal. Two weeks post-hepatectomy these activities had returned to normal. The activity of the 16 beta- and 2 beta-hydroxylation of testosterone was unchanged. However, the activity of 6 beta-hydroxylase decreased 7 days post-hepatectomy, while 16 alpha-hydroxylation had increased at 3 and 7 days post-hepatectomy compared with controls. 4. The changes in liver weight were nearly restored to preoperative levels 7 days post-hepatectomy. 5. Although the P450 content was unchanged from days 1 to 7 post-hepatectomy, it had decreased by 30% at day 14 and by 20% at day 28. The P4502B11 content 3, 7 and 14 days post-hepatectomy had increased 8, 10 and 2 times respectively, while the P4503A12 content at 7 and 14 days decreased by 30 approximately 50% compared with that of the pre-operative liver. 6. The data presented above do not reveal any relationship between P4502B11 induction and liver regeneration. The reason for such a change is unknown, therefore further investigation needs to be carried out.
Tanaka
E
E
Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan.
Osada
A
A
Ishikawa
A
A
Nakamura
T
T
Momose
Y
Y
Mikami
T
T
Fukao
K
K
Horie
T
T
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D000072467:Cytochrome P450 Family 2; D004114:Dimethadione / Q000097:blood / Q000378:metabolism; D004285:Dogs; D004790:Enzyme Induction; D006498:Hepatectomy; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D039181:Steroid 16-alpha-Hydroxylase; D014293:Trimethadione / Q000097:blood / Q000378:metabolism*
D000927:Anticonvulsants; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D004114:Dimethadione; D010105:Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D014293:Trimethadione