RT Journal Article
SR Electronic
T1 Age-related changes in glucuronidation and deglucuronidation in liver, small intestine, lung, and kidney of male Fischer rats.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 62
OP 67
VO 13
IS 1
A1 S J Borghoff
A1 L S Birnbaum
YR 1985
UL http://dmd.aspetjournals.org/content/13/1/62.abstract
AB Uridine diphosphoglucuronyltransferase (UDPGT) and beta-glucuronidase (beta G) activities were measured in liver, small intestine, lung, and kidney of male Fischer rats between the ages of 2 and 30 months in order to evaluate the balance between glucuronidation and deglucuronidation reactions as a function of age. Both enzyme activities were determined colorimetrically. UDPGT was measured using both p-nitrophenol (PNP) and phenolphthalein (PT) as substrates, while p-nitrophenyl-beta-D-glucuronide was used to measure BG activity. No age-related change was detected in small intestine or lung with either enzyme. UDPGT-PT activity was only detected in liver where its activity increased about 2-fold at 96 weeks of age and remained elevated. UDPGT-PNP activity displayed a maturational decrease up to 15 weeks in liver and then remained constant with age. BG activity was measured in both the microsomal and S9 fractions of these tissues. In liver, the microsomal BG activity remained constant with age. However, in the S9 fraction, this activity displayed an increasing trend after 24 weeks. BG activity in kidney microsomes also showed this increase in both fractions. UDPGT-PNP activity in kidney extract exhibited a gradual decreasing trend with age. If these results represent the in vivo situation, the changes in the balance between glucuronidation and deglucuronidation with age not only depend on the substrate, but also on the tissue. An emphasis is placed on separating out changes due to maturation or disease from those due to senescence.