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Ethanol-mediated CYP1A1/2 induction in rat skeletal muscle tissue.

Authors
Smith-C; Stamm-SC; Riggs-JE; Stauber-W; Harsh-V; Gannett-PM; Hobbs-G; Miller-MR
Source
Exp Mol Pathol 2000 Dec; 69(3):223-232
NIOSHTIC No.
20029513
Abstract
The causes of non-trauma-mediated rhabdomyolysis are not well understood. It has been speculated that ethanol-associated rhabdomyolysis may be attributed to ethanol induction of skeletal muscle cytochrome P450(s), causing drugs such as acetaminophen or cocaine to be metabolized to myotoxic compounds. To examine this possibility, the hypothesis that feeding ethanol induces cytochrome P450 in skeletal muscle was tested. To this end, rats were fed an ethanol-containing diet and skeletal muscle tissue was assessed for induction of CYP2E1 and CYP1A1/2 by immunohistochemical procedures; liver was examined as a positive control tissue. Enzymatic assays and Western blot analyses were also performed on these tissues. In one feeding system, ethanol-containing diets induced CYP1A1/2 in soleus, plantaris, and diaphragm muscles, with immunohistochemical staining predominantly localized to capillaries surrounding myofibers. Antibodies to CYP2E1 did not react with skeletal muscle tissue from animals receiving a control or ethanol-containing diet. However, neither skeletal muscle CYP1A1/2 nor CYP2E1 was induced when ethanol diets were administered by a different feeding system. Ethanol consumption can induce some cytochrome P450 isoforms in skeletal muscle tissue; however, the mechanism of CYP induction is apparently complex and appears to involve factors in addition to ethanol, per se.
Keywords
Ethanols; Muscle-tissue; Laboratory-animals; Animals; Animal-studies; Skeletal-system; Skeletal-system-disorders; Musculoskeletal-system-disorders; Enzymes
Contact
Department of Biochemistry, P.O. Box 9142, West Virginia University Health Sciences Center, Morgantown, WV 26506-9142
CODEN
EXMPA6
CAS No.
64-17-5
Publication Date
20001201
Document Type
Journal Article
Email Address
mmiller@hsc.wvu.edu
Funding Amount
868663
Funding Type
Grant
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-002918
Issue of Publication
3
ISSN
0014-4800
Priority Area
Disease and Injury: Musculoskeletal Disorders of the Upper Extremities
Source Name
Experimental and Molecular Pathology
State
WV
Performing Organization
West Virginia University, Morgantown, West Virginia
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