Cocaine is hepatotoxic in several species, including man. A high dose of
cocaine produces metabolism-dependent, mainly pericentral, liver damage. At 24 h after a single dose of
cocaine, mouse hepatic P450 content decreases but
CYP2A activities;
coumarin 7-hydroxylase and
testosterone 15 alpha-
hydroxylase increase concomitant with prominent diffuse cell
necrosis. Repeated administration of
cocaine for up to 5 days decreases
CYP1A1/2, 2A4/5, 2Cx, and 2E1 related enzymatic activities. However, after five doses of
cocaine, CYP2B10 increases in conjunction with the healing process. In the acute phase, the increased
CYP2A activities do not participate in
cocaine bioactivation.
CYP3A enzymes are principally responsible for the
cocaine N-demethylation in human and mouse liver microsomes. The hepatic metabolic CYP
enzyme profile will change during prolonged
cocaine intake, this being accompanied by altered cell morphology. Possible connections to
cocaine toxicity in man are discussed.