Alimentary TractEffects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers☆,☆☆,★
Section snippets
Subjects
This study was performed in 10 healthy volunteers (5 men and 5 women). All subjects were between 18 and 65 years of age, received no prescription or over-the-counter medications for the 2 weeks before the study, and had no significant medical problems. Individuals with a history of smoking or regular alcohol use were excluded. The study was approved by the University of Michigan Institutional Review Board. Written informed consent was obtained from all subjects.
Experimental design
Subjects were admitted to the
Results
Ten healthy adult volunteers (5 men and 5 women) participated in this 12-day inpatient study. The mean age of the 10 subjects was 23.4 years (range, 19–41), and mean subject weight was 66.4 kg (range, 44–85). Each subject received an inducer-free “washout” diet for 5 days, followed by a chargrilled meat–enriched diet for 7 days as described in Subjects and Methods.
Discussion
The aim of this study was to determine if a diet enriched with PAH and HA would induce intestinal and hepatic CYP3A, CYP1A, and Pgp levels in healthy volunteers. Despite the confirmed high levels of PAH and HA in the diet (Table 1), we found no evidence for induction of CYP3A enzymes in either liver, small intestine (Figure 1), or colon. Likewise, we found no evidence for induction of Pgp in the intestine (Figure 2) or colon. This finding is somewhat surprising in light of the known
Acknowledgements
The authors thank Cynthia P. Salmon, Lawrence Livermore National Laboratory, for the heterocyclic amine analysis and Che-Han Hsu for assistance in performing the polycyclic aromatic hydrocarbon analyses.
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Supported by National Institutes of Health grants GM38149-11 (to P.B.W.), GM53095-01 (to K.S.L.), and MO1RR00042 (to University of Michigan General Clinical Research Center).
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Address requests for reprints to: Paul B. Watkins, M.D., University of Michigan Medical Center, 1500 East Medical Center Drive, 2150 CCGC 0903, Ann Arbor, Michigan 48109. e-mail: [email protected]; fax: (734) 647-9554.
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Heterocyclic amine analysis was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract W-7405-Eng-48, supported by National Cancer Institute agreement YO1CP2-0523-01 and grant CA55861 from the National Cancer Institute.