TITLE:
Xenobiotic-Metabolizing Enzymes in Skeletal Muscle of Children and Adolescents
AUTHORS:
Dora Molina-Ortiz, José Francisco González-Zamora, Rafael Camacho-Carranza, Ocarol Lopez-Acosta, Oscar Colin-Martinez, Adriana Miriam Domínguez-Ramírez, Araceli Vences-Mejía
KEYWORDS:
Cytochrome P450; Skeletal Muscle; Children; Adolescents
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.4 No.2,
April
18,
2013
ABSTRACT: 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.