Effect of host-mediating anti-tumor drugs on hepatic δ-aminolevulinic acid synthetase and heme oxygenase activity in mice

Abstract

Effect of host-mediating anti-tumor drugs, OK-432 and PSK, on hepatic δ-aminolevulinic acid synthetase (ALA synthetase) and heme oxy genase activity was examined. Both OK-432 and PSK were shown to inhibit ALA synthetase activity when administered in vivo to mice. Both OK-432 and PSK also inhibited the 3,5-dicarboethoxy-1,4-dihydro collidine (DDC)-mediated induction of ALA synthetase when administered 12 and 16 h prior to the inducer. Additionally, the administration of OK-432 and PSK resulted in a significant increase in hepatic heme oxy genase activity. These data suggest that the decrease of hepatic drug-metabolizing enzymes as well as cytochrome P-450 levels seen on the administration of OK-432 and PSK is the result of the inhibition of ALA synthetase and of the increase of heme oxygenase activity leading to a decreased heme moiety required for the synthesis of cytochrome P-450 in the liver.