title: Age-related changes in hepatic activity and expression of detoxification enzymes in male rats.
abstract: Process of aging is accompanied by changes in the biotransformation of xenobiotics and impairment of normal cellular functions by free radicals. Therefore, this study was designed to determine age-related differences in the activities and/or expressions of selected drug-metabolizing and antioxidant enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6-week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using immunoblotting. Remarkable age-related decrease in specific activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes with advancing age were found. On the other hand, specific activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats compared with the young ones, respectively. Interindividual variability in CBR1 activity increased significantly with rising age. We suppose that elevated activities of GST and CBR1 may protect senescent rats against xenobiotic as well as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism of drugs, which are CBR1 and especially GSTs substrates.
authors: Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic.
authors: Erika
authors: E
authors: Vyskočilová
authors: Barbora
authors: B
authors: Szotáková
authors: Lenka
authors: L
authors: Skálová
authors: Hana
authors: H
authors: Bártíková
authors: Jitka
authors: J
authors: Hlaváčová
authors: Iva
authors: I
authors: Boušová
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004789:Enzyme Activation; D008658:Inactivation, Metabolic / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008657:Metabolic Clearance Rate; D010088:Oxidoreductases; D004364:Pharmaceutical Preparations; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D000975:Antioxidants; D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D010088:Oxidoreductases
references: Mol Biotechnol. 2007 Sep;37(1):58-61
references: 17914165
references: J Biol Chem. 1964 Jul;239:2370-8
references: 14209971
references: Biochem Pharmacol. 2008 Sep 15;76(6):773-83
references: 18671949
references: Free Radic Biol Med. 2002 Nov 1;33(9):1167-72
references: 12398924
references: Free Radic Res. 2006 May;40(5):495-505
references: 16551576
references: Mol Cells. 2003 Dec 31;16(3):278-84
references: 14744015
references: Drug Metab Dispos. 2008 Oct;36(10):2113-20
references: 18635746
references: Mayo Clin Proc. 1988 Apr;63(4):381-9
references: 2832662
references: Biochem Pharmacol. 1994 Mar 2;47(5):763-73
references: 8135852
references: Drug Metab Rev. 2009;41(2):67-76
references: 19514965
references: Phytochemistry. 2002 Jul;60(6):573-80
references: 12126703
references: Clin Chim Acta. 1991 Feb 15;196(2-3):143-51
references: 2029780
references: Pharmacol Rep. 2012;64(3):698-705
references: 22814022
references: J Pharmacol Exp Ther. 2004 May;309(2):720-9
references: 14742746
references: Toxicol Pathol. 2010 Jan;38(1):96-109
references: 20019356
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Jpn J Pharmacol. 1993 Sep;63(1):65-71
references: 8271533
references: Am J Physiol. 1990 Apr;258(4 Pt 2):R918-23
references: 2331035
references: Methods Enzymol. 1984;105:114-21
references: 6727659
references: Drug Metab Rev. 2012 Dec;44(4):267-86
references: 22998389
references: Biochem Pharmacol. 2004 Jul 1;68(1):73-83
references: 15183119
references: Arch Toxicol. 2010 Dec;84(12):939-46
references: 20130842
references: Biochim Biophys Acta. 1991 Apr 29;1077(3):325-31
references: 2029531
references: Drugs Aging. 2001;18(11):837-51
references: 11772124
references: Biogerontology. 2013 Feb;14(1):63-71
references: 23179288
references: Biochem Pharmacol. 1994 Aug 30;48(5):923-36
references: 8093105
references: Clin Chem. 1992 Jan;38(1):66-70
references: 1733608
references: Exp Gerontol. 2004 Feb;39(2):211-6
references: 15036414
references: Pharmacol Toxicol. 1994 Jul;75(1):1-6
references: 7971729
references: Curr Med Chem. 2007;14(7):745-57
references: 17346160
references: Arch Toxicol. 2004 Mar;78(3):131-8
references: 14600803
references: Annu Rev Nutr. 2001;21:453-73
references: 11375445
references: Biochem Pharmacol. 2002 Mar 1;63(5):889-96
references: 11911841
references: Xenobiotica. 1988 Nov;18(11):1225-37
references: 3149822
references: Indian J Clin Biochem. 2010 Oct;25(4):398-400
references: 21966113
references: J Biol Chem. 2009 May 1;284(18):11913-21
references: 19254950
references: J Biol Chem. 2002 Jul 5;277(27):24799-808
references: 11978787
references: Physiol Rev. 2002 Jan;82(1):47-95
references: 11773609
references: Biochem Biophys Res Commun. 1981 Jan 15;98(1):147-53
references: 7213381
references: Toxicol Appl Pharmacol. 1994 Mar;125(1):1-6
references: 8128486
references: Anal Biochem. 1985 Oct;150(1):76-85
references: 3843705
references: J Pharmacobiodyn. 1982 Oct;5(10):811-7
references: 7161709
references: Eur J Drug Metab Pharmacokinet. 2005 Jan-Jun;30(1-2):3-17
references: 16010857
references: Clin Chim Acta. 2001 Mar;305(1-2):75-80
references: 11249925
references: Biochem Pharmacol. 1997 Jul 1;54(1):159-64
references: 9296362
references: Drug Metab Dispos. 2006 Jan;34(1):19-26
references: 16183778
references: Xenobiotica. 1988 Nov;18(11):1211-24
references: 3149821
references: Biogerontology. 2010 Feb;11(1):103-9
references: 19430956
references: Drug Discov Today. 2007 Aug;12(15-16):599-610
references: 17706541
references: Physiol Res. 2010;59(4):553-560
references: 19929140
references: Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4
references: 388439
references: Proc Soc Exp Biol Med. 1991 Jul;197(3):297-303
references: 1906180
references: J Biol Chem. 1974 Nov 25;249(22):7130-9
references: 4436300