Diminished Enhancement of Hepatic UDP Glucuronyl Transferase (Bilirubin) by Phenobarbital during Pregnancy in the Rat

Abstract

UDP glucuronyl transferase (bilirubin) (UDPGT) was studied in liver homogenates of pregnant and nonpregnant adult female rats. No change in maternal liver UDPGT activity was observed during pregnancy. Administration of phenobarbital (PB) for the 3 days preceding enzyme assay increased UDPGT activity in nonpregnant rats by 61.8%. The same treatment of pregnant rats produced a similar increase in UDPGT activity measured on the 5th, 7th and 9th day of gestation. After day 9, the extent of this PB-mediated increase in hepatic UDPGT activity progressively decreased, and by the 21st day of gestation the increase was only 19.0 %. This observation of reduced response of UDPGT (bilirubin) after PB administration during late pregnancy in the rat, may be significant in understanding the mechanism of neonatal glucuronyl transferase deficiency as well as drug metabolism in mother and fetus.

Xylose, Glucose, and Glucuronic Acid Conjugation of Bilirubin in the Newborn Rat

“…The failure to induce the enzyme during the first 4 days of life may relate to differences in species, strain, dosage, metabolism of PB, and enzyme assay techniques. Although metabolites of phenobarbital were not determined in the present study, fetal and newborn phenobarbital concentrations in rats were found to be identical with maternal hepatic concentrations (19). In the present assay system, whole homogenates were used.…”

Various Bilirubin Conjugates in Pregnant and Nonpregnant Rats with and without Phenobarbital Treatment

“…housed, fed. treated with PB ( I00 mg/kg/24 hr s.c. for 3 days) and killed in exactly the same manner as described in our previous study (8). Livers were removed immediately after time of killing, washed in cold 0.154 M KCI.…”

“…The degree of response of maternal hepatic bilirubin glucuronide formation to P B stimulation during the second half of pregnancy has recently been found to be significantly less than in nonpregnant or early pregnant rats. despite similar hepatic phenobarbital concentrations (8). At 21 days of gestation (term) the increase in glucuronyl transferase activity was approximately one-third of that in early pregnancy (8).…”

“…despite similar hepatic phenobarbital concentrations (8). At 21 days of gestation (term) the increase in glucuronyl transferase activity was approximately one-third of that in early pregnancy (8). Although hepatic conjugation of bilirubin in mammalian species is predorninontly with glucuronic acid to form the water-soluble, excretable form of bile pigment, significant quantities of glucose and xylose conjugates have also been identified in bile ( I ) .…”