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Toll-Like Receptor-4 Regulation Of Hepatic Cyp3a11 Metabolism In A Mouse Model Of Lps-Induced Cns Inflammation, Kerry B. Goralski, Dalya Abdulla, Christopher J. Sinal, Andre Arsenault, Kenneth W. Renton
Toll-Like Receptor-4 Regulation Of Hepatic Cyp3a11 Metabolism In A Mouse Model Of Lps-Induced Cns Inflammation, Kerry B. Goralski, Dalya Abdulla, Christopher J. Sinal, Andre Arsenault, Kenneth W. Renton
Faculty Publications and Scholarship
Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 μg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-α and/or IL-1β proteins in the brain. In all mouse strains, LPS produced a 60–70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding …