Effect of low-dose phenobarbital on hepatic microsomal UDP-glucuronyl transferase activity |
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Authors: | N Tavoloni R Wittman M J Jones P D Berk |
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Institution: | Polly Annenberg Levee Hematology Center (Department of Medicine) and Department of Physiology, Mount Sinai School of Medicine, New York, NY 10029, U.S.A. |
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Abstract: | To determine whether hepatic microsomal enzyme induction occurs in rats following administration of phenobarbital at doses similar to those used in humans (0.5 to 7.5 mg/kg), UDP-glucuronyl transferase (UDPGT) and cytochrome P-450 activities were measured in liver homogenate and microsomal preparations from control rats and rats treated for 6 days with phenobarbital at 1 and 3 mg per kg per day. While no significant increases in liver weight and protein content of homogenate and microsomal preparations were observed with either dose of the drug, both UDPGT and P-450 activities were enhanced significantly following administration of phenobarbital at 3 mg per kg per day. The activity of P-450 was increased by approximately 30% and that of UDPGT by 15-24 and 45-66%, respectively, employing bilirubin and p-nitrophenol as the acceptor substrate. The extent of induction of bilirubin or p-nitrophenol UDPGT was similar when measured with "native" enzyme or with enzyme activated by UDP-N-acetyl glucosamine, digitonin or deoxycholate. These data suggest that the discordant effects of phenobarbital on UDPGT and cytochrome P-450 previously reported in humans and rats may not be attributable solely to differences in the drug doses employed. |
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Keywords: | UDPGT uridine-5′-diphosphate glucuronyl transferase (EC 2 4 1 17) and UDPNAG Address all correspondence to: Paul D Berk M D Polly Annenberg Levee Hematology Center Mount Sinai School of Medicine 1 Gustave L Lew Place New York NY 10029 U S A |
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