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Ethanol-mediated induction of CYP1A1/2 in rat skeletal muscle.
Miller-MR; Smith-C; Stamm-SC; Riggs-JE; Stauber-W; Harsh-V; Gannett-PM
Toxicologist 1999 Mar; 48(1-S):98
This study tested the hypothesis that feeding rats an ethanol-containing diet would induce CYP2E1 and/or CYPIA 1/2 in skeletal muscle tissue; these cytochrome P450 enzymes were also analyzed in liver, as a positive control tissue. Enzymatic assays, p-nitrophenol (PNP, for CYP2E1) and ethoxyrdorufin O-deethylase (EROD, for CYPIA1/2), as well as Western blot analysis, demonstrated that a liquid diet containing 6% ethanol and delivered via a feeding system using glass bottles and rubber stoppers with a stainless steel tube (Feeding System 1) induced CYP2E1 and CYP1A1/2 in liver tissue. Immunocytochemistry studies confirmed induction of these liver enzymes by the ethanol-containing diet. Imrnunohistochemical analysis of skeletal musclee (soleus, plantaris, and diaphragm) indicated ethanol-containing diets administered by Feeding System 1 induced CYPIA1/2, and immunohistochemical staining was predominantly localized to capillaries currounding myofibers. However, antibodies to CYP2E1 did not detectably react with skeletal muscle tissue from animals receiving a control or ethanol-containing diet. Identical results were obtained when highly purified ethanol was preparedd and administered in the diets. However, when liquid diets were administered via Feeding System 2 (all-glads feeding system), CYP1A1/2 was not induced by ethanol-containing diets in liver or in skeletal muscle tissue; CYP2E1 was induced in liver by Feeding System 2. The results indicate that feeding ethanol can mediate induction of CYPIAl/2 in liver and in capillaries of skeletal muscle; however, this induction was not attributed to ethanol per se, but rather to an unidentified compound(s) apparently solubilized by 6% ethanol from robber stoppers or stainless steel tubing.
Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Liver; Skeletal-disorders; Skeletal-system; Skeletal-system-disorders
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
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