Effect of low-dose phenobarbital on hepatic microsomal UDP-glucuronyl transferase activity

Biochemical Pharmacology
N TavoloniP D Berk

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.

References

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Citations

May 1, 1997·Experimental Gerontology·A PlewkaD Plewka
Feb 1, 1987·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C J HoleskiG M Bellamy
Dec 31, 1987·Biochemical and Biophysical Research Communications·D SorrentinoP D Berk
Dec 1, 1986·British Journal of Clinical Pharmacology·D E PriceM P Feely

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