BIOCHEMICAL CHANGES IN RAT LIVER IN RESPONSE TO TREATMENT WITH DRUGS AND OTHER AGENTS .3. EFFECTS OF CENTRALLY ACTING DRUGS

In this third paper, results are presented on the effects on various rat liver parameters of chronic administration of several agents with activity in the central nervous system. Three patterns of response were found with the nine agents examined. Two of the groups were virtually identical except that the glutethimide group induced liver enlargement whereas the chlorpromazine-group did not. Both groups showed marked elevation of microsomal drug metabolism. Eight of the nine agents showed elevation of microsomal NADH2-cyt. c reductase activity. An overall discussion of the results in this and the two precedings papers is presented which suggests that toxicity and liver enlargement can be separated by biochemical means and that drug-induced liver enlargement is not necessarily a toxic response of the liver but can be a functional response. Evidence for the primary involvement of the endoplasmic reticulum is presented and an hypothesis is advanced in an attempt to simplify and rationalise the interpretation of the effects of foreign agents on the liver. © 1969.