HEPATIC REGENERATION IS ASSOCIATED WITH PRESERVATION OF MICROSOMAL GLUCURONIDATION

Significant controversy exists regarding the regulation of glucuronida tion during the process of hepatic regeneration, We used a partial hep atectomy rat model to elucidate the effects of hepatic regeneration on the various components of the microsomal glucuronidation system. Hepa tic microsomes were prepared by standard sucrose density centrifugatio n, coupled with a modified technique involving Percoll centrifugation, Micro somal uridine diphosphate (UDP) -glucuronosyltransferase (UGT) protein expression and UGT messenger RNA (mRNA) levels were measured b y Western and Northern blotting, UGT enzyme activity was determined to ward two prototypical aglycones, p-nitrophenol and estrone, in intact and digitonin-treated microsomes, Microsomal uptake of the cosubstrate for all glucuronidation reactions, UDP-glucuronic acid (UDP-GlcUA), w as determined using a rapid-filtration assay, Microsomal enrichment af ter hepatectomy was preserved only when the Percoll method was used. M icrosomal UGT protein expression and UGT mRNA levels were unaltered af ter hepatectomy. UGT enzyme activity toward estrone was unchanged 1 da y posthepatectomy compared with sham laparotomy controls, Similarly, p -nitrophenol glucuronide formation was unaffected by hepatic regenerat ion 1, 2, and 5 days posthepatectomy when digitonin-treated microsomes were used, Glucuronidation of p-nitrophenol in intact microsomes was increased in partial hepatectomy compared with sham-operated controls at 1 and 2 days. This increase was not attributable to changes in micr osomal UDP-GlcUA uptake, which was comparable in both groups, We concl ude that microsomal glucuronidation, in contrast to other well charact erized hepatic metabolic functions, is highly preserved during liver r egeneration.