Effect of Traumatic Brain Injury, Erythropoietin and Anakinra on Hepatic Metabolizing Enzymes and Transporters in an Experimental Rodent Model. Rattus norvegicus

In contrast to the considerable in vitro and in vivo data demonstrating a decrease in cytochrome P450 (CYP) activity in inflammation and infection, clinically, traumatic brain injury (TBI) results in an increase in CYP and UDP glucuronosyltransferases (UGT) activity. The objective of this study was to determine the effects of TBI alone and along with treatment with either erythropoietin (EPO) or anakinra on gene expression of hepatic inflammatory proteins and drug metabolizing enzymes and transporters in a cortical contusion impact (CCI) injury animal model. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h and 7 days post-CCI. Overall design: Fifty male Sprague Dawley rats (Harlan, Indianapolis, IN) approximately three months of age (335 ± 28 g) were used in this study. Animals were randomly assigned to one of four groups: (a) Intact sham, (b) CCI-injured + EPO 2,500 IU/kg (Procrit, Amgen, Thousand Oaks,CA) (c) CCI-injured + anakinra 100 mg/kg (Kineret, Amgen, Thousand Oaks, CA) and (d) CCI-injured + vehicle (saline). Five intact sham animals and five animals in each treatment group at specified time points post-CCI (24 h, 72 h and 7 days) were overdosed with a mixture of CO2 (80%) and O2 (20%). The rats were then decapitated; a cardiac blood sample collected, brains and livers were rapidly extracted. The median lobe of the liver was extracted and placed on ice. Six tissue punches were collected and placed into microcentrifuge tubes, snap frozen and then stored at -80º C.