Xenobiotic-Metabolizing Enzymes in Skeletal Muscle of Children and Adolescents

摘要

Cytochrome P450 (CYP) enzymes metabolize endogenous compounds such as steroid hormones, fatty acids, and xenobiotics, including drugs and carcinogens. The skeletal muscle is highly exposed to circulating xenobiotics; nevertheless the knowledge on the expression of these enzymes not only in adult skeletal muscle but also in younger individuals has been very little. Therefore, the aim of the present study was to investigate the expression of CYP enzymes in healthy skeletal muscles of children and adolescents. This was investigated in a total of 18 biopsies taken from the quadriceps skeletal muscle of younger patients: 9 boys and 9 girls (≤18 years) by using specific antibodies in immunoblots and by RT-PCR mRNA analysis. The mRNA transcripts for CYP1B1 and CYP2E1 were consistently detected in all samples, but in the immunoblot only was identified CYP1B1 protein in four samples. Regarding CYP1A1, CYP3A4 and CYP3A5 enzymes in skeletal muscle, there were found in some samples in both techniques, although with significant inter-individual variations. Finally CYP2W1 only was detected in one sample belonging to the youngest patient. These data show that a range of CYP enzymes are expressed in the skeletal muscle of children and adolescents, suggesting that the metabolism of several xenobiotic chemicals to which humans are exposed takes place in muscle cells. Moreover, since the potential participation of muscles is a fact in pharmacokinetics of many therapeutic drugs, expression of CYPs in skeletal muscle may play an important role in drug-dependent toxicity.