Effects of aging and long-term caloric restriction on hepatic microsomal monooxygenases in female fischer 344 rats: Alterations in basal cytochrome P-450 catalytic activities |
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Authors: | Michail Alterman Michael Carvan Vinod Srivastava Julian Leakey Ron Hart David Busbee |
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Institution: | (1) Department of Anatomy and Public Health, College of Veterinary Medicine, Texas A & M University, College Station, TX, 77843;(2) Department of Physiology, College of Medicine, Texas A & M University, College Station, TX, 77843;(3) National Center for Toxicological Research, Jefferson, AR, 72079 |
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Abstract: | The effects of aging and caloric restriction on uninduced levels of hepatic microsomal cytochrome P-450s and specific P-450-related
catalytic activities were evaluated in female Fischer 344 rats. Microsomes were isolated from livers of ad libitum (AL) fed rats 1, 3, 6, 16 and 26 months of age, and from calorie-restricted (CR) rats 6, 16 and 26 months of age. The recovery
of microsomal protein was higher in CR than AL rats at 6, 16 and 26 months of age. Between ages 3 and 26 months there was
a gradual decline in recovered microsomal P-450, but the differences between successive age categories were not significant.
A different trend was observed for total cytochrome P-450 per liver. AL rats showed a 2-fold decline in P-450/liver between
6 and 26 months of age, while P-450/liver of corresponding CR rats increased 1.7-fold. Neither cytochrome b5 nor NADPH cytochrome C reductase varied consistently as a function of increased age, with all age groups showing greater
reductase activity for CR rats than for AL rats. Phenobarbital (PB) and methylcholenthrene (MC) inducible cytochrome P-450
catalytic activities (pentoxy PROD] and ethoxy EROD] resorufin O-deethylases) exhibited similar age-related alterations
that were distinctly different from the two other enzymes examined. Both PROD and EROD showed dramatic declines in activity
between 1 and 3 months of age, with a slight increase in activity at 6 months and maintenance of the activity levels through
26 months. Benzphetamine N-demethylase (BND) and aniline p-hydroxylase (APH) activities were also altered as a function of
increased age, with CR rats exhibiting increased isozyme activity above that seen for aging AL rats. Calorie restriction appears
to have a modulating effect, compensating for an age-related decline of hepatic microsomal monooxygenase activity in female
Fischer 344 rats. |
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