Abstract
Interest in the non-neuronal alterations following traumatic brain injury (TBI) has led to research evaluating hepatic metabolism following injury. Several models of injury demonstrate tissue-specific alterations in cytochrome P450 activity. This study examined tissue-specific alterations in cytochrome P450-mediated hydroxylation in the rat model of TBI. Male Sprague-Dawley rats received anesthesia alone, craniotomy, or craniotomy plus TBI. Rats were sacrificed at 24 and 48 h. Liver, kidney, and brain cortex microsomes were isolated. Total liver P450 content, 6-hydroxychlorzoxazone formation rate, and CYP2E1 protein were evaluated. In liver microsomes, spectral P450 was decreased to 86 ± 5% (p < 0.05) of control at 24 h following injury, and 6-hydroxychlorzoxazone formation rate decreased to 74 ± 18% of control (p < 0.05) at 48 h following injury. In kidney microsomes, 6-hydroxychlorzoxazone formation rate was increased to 154% of control (p < 0.01) 24 h following injury. 6-Hydroxychlorzoxazone formation rate was unaffected by TBI in brain cortical microsomes. The CYP2E1 inhibitor, 4-methylpyrazole, inhibited the formation of 6-hydroxychlorzoxazone in brain, kidney, and liver microsomes. These data demonstrate that tissue-specific alterations in 6-hydroxychlorzoxazone formation rate occur following TBI.
Footnotes
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Send reprint requests to: Samuel M. Poloyac, Dept. of Pharmaceutical Sciences, University of Pittsburgh, 1014 Salk Hall, 3500 Terrace St., Pittsburgh, PA 15261. E-mail: poloyac+{at}pitt.edu
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This work was supported in part by Kentucky Spinal Cord and Head Injury Research Trust Grant 9502 (R.A.B.), National Institutes of Health, U.S. Public Health Service Grant NS39828 (S.W.S.), and the American Foundation for Pharmaceutical Education (S.M.P.).
- Abbreviations used are::
- TBI
- Traumatic brain injury
- CX
- craniotomy
- 4MP
- 4-methylpyrazole
- P450
- cytochrome P450
- Received June 20, 2000.
- Accepted December 4, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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Tissue-Specific Alterations in the 6-Hydroxylation of Chlorzoxazone Following Traumatic Brain Injury in the Rat
