Changes in expression of hepatic cytochrome P450 subfamily enzymes during development of adjuvant-induced arthritis in rats

Abstract

An animal model of rheumatoid arthritis can be elicited in male Lewis rats by a single intradermal injection of liquid paraffin containing dead Mycrobacterium tuberculosis (MT adjuvant) into the planar surface of the right hind-foot. In the present study, we used this animal model to examine the changes in expression of hepatic cytochorme P450 (CYP) enzymes during the development of the arthritis. Swellings of the MT adjuvant-injected hind-foot initially occurred at 1-8 days after the injection. Thereafter, the swelling gradually become more severe up to 13 days later and was maintained for up to 25 days. Swellings of the other hind-foot was also observed after 12 days and gradually become more severe up to 15 days with maintenance of the severe swelling for up to 25 days. The gene expression levels and enzyme activities of hepatic CYP 3A and CYP2B subfamily enzymes at 1, 12, and 25 days after the MT adjuvant injection were significantly decreased, compared with the corresponding time-matched controls. The decreases in the gene expression levels and activities of all the enzymes examined were closely correlated with increases in the expression levels of the inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, interleukin-1β and interleukin-6, which were produced in the liver. All of the present findings demonstrate that hepatic CYP3A and CYP2B subfamily enzymes are decreased during the development of MT adjuvant-induced arthritis and further suggest that the decreases are dependent on the production of inflammatory cytokines in the liver.