ENHANCEMENT OF INTESTINAL UDP-GLUCURONOSYLTRANFERASE ACTIVITY IN PARTIALLY HEPATECTOMIZED RATS

To evaluate whether a temporary hepatic insufficiency may affect intes tinal glucuronidation, we determined UDP-glucuronosyltransferase activ ity towards bilirubin and p-nitrophenol in rat jejunum and liver after partial hepatectomy. Enzyme assays mere performed in native, and in U DP-N-acetylglucosalnine- or palmitoyl lysophosphatidylcholine-activate d microsomes at different times post-hepatectomy. Content of enzyme wa s analyzed by Western blot. Microsomal cholesterol/phospholipid ratio, phospholipid and total fatty acid classes were also determined to eva luate the possible influence on enzyme activity. The results show that while hepatic microsomes exhibited no change in UDP-glucuronosyltrans ferase activity (for both substrates) with respect to shams at any tim e of study, intestinal activities increased significantly 48 h after s urgery, returning to sham values 96-h post-hepatectomy. Western blotti ng confirmed the increase (about 50% for both substrates 48-h post-hep atectomy) in intestinal UDP-glucuronosyltransferase activity. No varia tions were observed in hepatic and intestinal microsomal lipid composi tion in agreement with the absence of modification in the percent of a ctivation by palmitoyl lysophosphatidylcholine. In conclusion, jejunum but not liver, was able to produce a compensatory increase in conjuga tion capacity during a transitory loss of hepatic mass. The phenomenon is associated to a modification in the amount of UDP-glucuronosyltran sferase, rather than to changes in the characteristics of the enzyme e nvironment. (C) 1998 Elsevier Science B.V.