Reduced drug metabolism in isolated hepatocytes from adjuvant arthritic rats

Viable hepatocytes were isolated from the livers of rats with adjuvant arthritis by the collagenase-perfusion method and measured for activities of drug-metabolizing enzymes. These cells produced radioactive metabolites from 14C-aminopyrine and 14C-aniline to a much lesser extent than the control hepatocytes that were derived from pair-fed normal rats. On the other hand, 14C-aminopyrine was scarcely metabolized by non-parenchymal cells other than hepatocytes, even when incubated with those from control rats. Although there were no significant differences in cell yield, viability and oxygen consumption, the cellular uptake of indocyanine green was significantly slower in the arthritic hepatocytes than the control hepatocytes. Morphologically, the freshly isolated arthritic hepatocytes demonstrated the disappearance of the microvilli, the appearance of bleb-like protrusions in the plasma membrane and the widespread distribution of the rough endoplasmic reticulum associated with a relatively decreased area of the smooth endoplasmic reticulum in the cytoplasma. Biochemically, these cells showed a significantly higher RNA/DNA ratio and an ability to incorporate 14C-leucine into proteins more rapidly, as compared to the control hepatocytes. A possible relationship between the reduction of the drug metabolizing activity and the production of the acute phase proteins in rat hepatocytes after an inflammatory stimulus was discussed.