Biomaterial Database

Increased renal drug metabolism in treadmill-exercised Fischer-344 male rats. 1993

T S Piatkowski, and W W Day, and M Weiner

Department of Pharmacology and Toxicology, University of Maryland, Baltimore School of Pharmacy.

Renal cytochrome P-450 levels, metabolism of acetaminophen (APAP) and aminopyrine, and activities of several phase II-associated enzymes [UDPGT, beta-glucuronidase, and glutathione-S-transferase (GST)] were determined in sedentary and exercised young and middle-aged Fischer-344 male rats. After an 8-week exercise regimen consisting of treadmill running at a moderate intensity, renal microsomal cytochrome P-450 levels were increased 60% and 37% in young and middle-aged runners, respectively. Exercise was found to increase renal deacetylation of APAP to the nephrotoxic metabolite p-aminophenol by 54% in young and 26% in middle-aged rats. Aminopyrine N-demethylase activity was increased 97% in the young runners only. In contrast, UDPGT, beta-glucuronidase, and GST activities were unchanged by treadmill running. NADPH-cytochrome c reductase activity, determined in young animals only, was also unaltered by exercise. Advanced age decreased renal cortical cytochrome P-450 content by 34% while having no effect on p-aminophenol production. Aminopyrine N-demethylase activity was increased by 130% with increased age. The only phase II-associated enzyme altered by age was GST activity, as sedentary middle-aged animals exhibited a 43% decrease in activity when compared with young rats. Young exercised rats did not gain weight as rapidly as sedentary rats, and middle-aged rats had a slight loss in weight during exercise. Moreover, running resulted in 30-36% less food consumption during the experimental period. In conclusion, this study demonstrated that exercise increased renal phase I drug metabolism without influencing phase II processes; furthermore, a substrate-specific modification of the response to exercise was observed in the aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007672	Kidney Cortex	The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL.	Cortex, Kidney
D008297	Male		Males
D010805	Physical Conditioning, Animal	Diet modification and physical exercise to improve the ability of animals to perform physical activities.	Animal Physical Conditioning,Animal Physical Conditionings,Conditioning, Animal Physical,Conditionings, Animal Physical,Physical Conditionings, Animal
D011916	Rats, Inbred F344	An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes.	Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D005966	Glucuronidase		Endo-beta-D-Glucuronidase,Endoglucuronidase,Exo-beta-D-Glucuronidase,beta-Glucuronidase,Endo beta D Glucuronidase,Exo beta D Glucuronidase,beta Glucuronidase
D005982	Glutathione Transferase	A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.	Glutathione S-Alkyltransferase,Glutathione S-Aryltransferase,Glutathione S-Epoxidetransferase,Ligandins,S-Hydroxyalkyl Glutathione Lyase,Glutathione Organic Nitrate Ester Reductase,Glutathione S-Transferase,Glutathione S-Transferase 3,Glutathione S-Transferase A,Glutathione S-Transferase B,Glutathione S-Transferase C,Glutathione S-Transferase III,Glutathione S-Transferase P,Glutathione Transferase E,Glutathione Transferase mu,Glutathione Transferases,Heme Transfer Protein,Ligandin,Yb-Glutathione-S-Transferase,Glutathione Lyase, S-Hydroxyalkyl,Glutathione S Alkyltransferase,Glutathione S Aryltransferase,Glutathione S Epoxidetransferase,Glutathione S Transferase,Glutathione S Transferase 3,Glutathione S Transferase A,Glutathione S Transferase B,Glutathione S Transferase C,Glutathione S Transferase III,Glutathione S Transferase P,Lyase, S-Hydroxyalkyl Glutathione,P, Glutathione S-Transferase,Protein, Heme Transfer,S Hydroxyalkyl Glutathione Lyase,S-Alkyltransferase, Glutathione,S-Aryltransferase, Glutathione,S-Epoxidetransferase, Glutathione,S-Transferase 3, Glutathione,S-Transferase A, Glutathione,S-Transferase B, Glutathione,S-Transferase C, Glutathione,S-Transferase III, Glutathione,S-Transferase P, Glutathione,S-Transferase, Glutathione,Transfer Protein, Heme,Transferase E, Glutathione,Transferase mu, Glutathione,Transferase, Glutathione,Transferases, Glutathione
D000082	Acetaminophen	Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.	Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging