Hepatic Transcript Levels for Genes Coding for Enzymes Associated with Xenobiotic Metabolism are Altered with Age

Autor: Edward K. Lobenhofer, Joseph H. Roycroft, Joel S. Parker, Gary A. Boorman, Kimwa L. Walker, Kazuhiko Mori, Tiwanda Marsh, Pamela E. Blackshear, Denise Orzech, Kennita Johnson, Richard D. Irwin
Rok vydání: 2007
Předmět:
Male
Senescence
Aging
medicine.medical_specialty
Transcription
Genetic
040301 veterinary sciences
CYP3A
Toxicology
030226 pharmacology & pharmacy
Gene Expression Regulation
Enzymologic
Xenobiotics
Pathology and Forensic Medicine
0403 veterinary science
Transcriptome
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Toxicity Tests
medicine
Animals
Cytochrome P-450 CYP3A
Cytochrome P450 Family 2
Molecular Biology
Gene
Oligonucleotide Array Sequence Analysis
biology
Age Factors
Membrane Proteins
Reproducibility of Results
Cytochrome P450
04 agricultural and veterinary sciences
Cell Biology
Metabolism
Rats
Inbred F344
Rats
Endocrinology
Liver
Steroid 16-alpha-Hydroxylase
Biochemistry
chemistry
biology.protein
Aryl Hydrocarbon Hydroxylases
Xenobiotic
Drug metabolism
Zdroj: Toxicologic Pathology. 35:242-251
ISSN: 1533-1601
0192-6233
DOI: 10.1080/01926230601156286
Popis: Metabolism studies are crucial for data interpretation from rodent toxicity and carcinogenicity studies. Metabolism studies are usually conducted in 6 to 8 week old rodents. Long-term studies often continue beyond 100 weeks of age. The potential for age-related changes in transcript levels of genes encoding for enzymes associated with metabolism was evaluated in the liver of male F344/N rats at 32, 58, and 84 weeks of age. Differential expression was found between the young and old rats for genes whose products are involved in both phase I and phase II metabolic pathways. Thirteen cytochrome P450 genes from CYP families 1–3 showed alterations in expression in the older rats. A marked age-related decrease in expression was found for 4 members of the Cyp3a family that are critical for drug metabolism in the rat. Immunohistochemical results confirmed a significant decrease in Cyp3a2 and Cyp2c11 protein levels with age. This indicates that the metabolic capacity of male rats changes throughout a long-term study. Conducting multiple hepatic microarray analyses during the conduct of a long-term study can provide a global view of potential metabolic changes that might occur. Alterations that are considered crucial to the interpretation of long-term study results could then be confirmed by subsequent metabolic studies.
Databáze: OpenAIRE
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