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.
Highlights
The role of skeletal muscle as a site of extrahepatic xenobiotic metabolism has not been sufficiently addressed, despite accounting for around 45% of total body weight and it is characterized by high metabolic rate and blood flow
We initially investigated the expression of some Cytochrome P450 (CYP) enzymes in human skeletal muscle using Quantitative Polymerase Chain Reaction (qPCR) gene expression analyses of metabolizing enzymes (CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, CYP3A5)
We have established for the first time the expression pattern of xenobiotic metabolizing CYPs in human skeletal muscle in children and adolescents
Summary
The role of skeletal muscle as a site of extrahepatic xenobiotic metabolism has not been sufficiently addressed, despite accounting for around 45% of total body weight and it is characterized by high metabolic rate and blood flow. This later characteristic makes it highly exposed to circulating drugs with 13% - 98% binding ability [1]. It has been recognized that numerous drugs have been reported to possess myotoxic effects [4] such as weakness, tenderness, and rhabdomyolysis These therapeutics drugs include neuromuscular-blocking agents, antihistamines, diuretics, antibiotics, chemotherapy drugs, and high-dose steroids [5]. The expression profile of metabolizing enzymes in the muscle tissue may play a major role in drug myotoxicity
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