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An investigation into the role of rat skeletal muscle as a site for xenobiotic metabolism using microsomes and isolated cells

Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, NE2 4HH UK

PG Blain

Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, NE2 4HH UK

Faith M Williams

Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, NE2 4HH UK

1 The role of skeletal muscle microsomes as a site of extrahepatic xenobiotic metabolism using n-hexane as a model substrate was investigated. The observed cytochrome P450-dependent metabolism was com pared with that found with liver, and brain micro somal fractions.

2 Rat skeletal muscle microsomes metabolised n-hexane to 1-, 2- and 3-hexanol at rates 40 - 300 times lower than observed with rat liver microsomes.

3 Fast-twitch extensor digitorum longus muscle (EDL) microsomes had twice as much n-hexane hydroxylase activity as the slow-twitch soleus and furthermore the EDL microsomes produced 2-hexanol, a bioactivation product of n-hexane, as a major metabolite.

4 Metabolism of hexane to 1-, 2- and 3- hexanol and 2- hexanone was demonstrated in cultured rat myoblasts.

5 Ethoxyresorufin and pentoxyresorufin O-dealkylation were not detected in either muscle microsomes or myoblasts although immunocytochemical localisation studies were suggestive of the presence of cytochrome P-450.

6 In conclusion, rat skeletal muscle has a low level of xenobiotic metabolism activity. The relevance to neuromuscular toxicity of n-hexane is discussed.

Key Words: n-Hexane • skeletal muscle • metabolism myopathy • myoblast

Human & Experimental Toxicology, Vol. 16, No. 3, 138-145 (1997)
DOI: 10.1177/096032719701600302


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