The role of microsomal beta-glucuronidase in ascorbic acid biosynthesis stimulated by xenobiotics in rats.

We (Horio et al., 1993) have reported that the stimulation of the expression of the UDPglucuronosyltransferase (UDPGT) gene played a key role in the ascorbic acid biosynthesis induced by xenobiotics, such as 3-methylcholanthrene (3MC) and phenobarbital (PB). beta-Glucuronidase catalyzes the hydrolysis of glucuronide formed by UDPGT. The role of microsomal beta-glucuronidase in ascorbic acid biosynthesis induced by xenobiotics was investigated using homozygous and heterozygous EHBRs (Eisai hyperbilirubinuria rats) which are deficient in microsomal beta-glucuronidase. Homozygous EHBRs, heterozygous EHBRs, and Sprague Dawley (SD) rats were injected intraperitoneally once with 3MC (20 mg/kg body weight), or once a day for 2 d with PB (100 mg/day kg body weight). In these three strains of rats, the hepatic level of xenobiotics-inducible UDPGT mRNA was elevated similarly by the treatment with xenobiotics. The increases of the hepatic concentration of ascorbic acid and the urinary excretion of ascorbic acid by the treatment with 3MC or PB were markedly suppressed in both EHBRs compared with those in the control SD rats. These results indicate that the microsomal beta-glucuronidase has an important role in the hepatic ascorbic acid biosynthesis induced by xenobiotics.