Main Article Content
aging, cytochrome P450s, exercise, nuclear receptors, rat, swimming
Background and Objective
Cytochrome P450s (CYPs) are the major drug-metabolizing enzymes responsible for the clearance of approximately 75% of all drugs in clinical use. Drug clearance may be reduced with aging, resulting in increased drug toxicity in the elderly. Here, we evaluated changes in CYP expression following exercise in an aging rat model.
Materials and Methods
Sixteen male Sprague-Dawley rats were grouped into control (n=5), short-term exercise (SE) (n=4), and long-term exercise (LE) (n=7) groups and changes in CYPs and nuclear receptors (NRs) were measured with aging.
CYP2C22, CYP3A1, and CYP2C11 mRNAs were upregulated, whereas CYP26B1 was downregulated in the SE and LE groups compared with the control group. Moreover, mRNA levels of the NRs, constitutive androstane receptor, retinoid X receptor α, peroxisome proliferator-activated receptor, and pregnane X receptor, were significantly increased in the LE group compared with those in the control group. As an indicator of more long-term changes, protein levels of CYP2C11, CYP2B, CYP1A, CYP2C, and CYP2C22 were significantly upregulated in the LE group compared with the control group. Overall, our data show that CYP and NR expression increased in rats with forced long-term exercise during aging.
Therefore, we propose that regular swimming exercise may increase CYP levels, resulting in enhanced drug clearance and thereby reducing age-related drug toxicity in elderly individuals.
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