Role of isosafrole as complexing agent and inducer of P-450LM4 in rabbit liver microsomes.

Isosafrole serves as an excellent inducing agent in rabbits for Wq, the same isozyme as that which is induced by 3-methylcholanthrene and 5,6-benzoflavone. Since the isosafrole adduct formed with isozyme 4 is unstable, the uncomplexed cytochrome may be purified in very good yield (over 30%, based on total P-450) from liver microsomes of animals given this agent. Isosafrole forms adducts with both isozyme 2 (the phenobarbital-inducible form of P-450) and isozyme 4 in the reconstituted system containing NADPHcytochrome P-450 reductase, phosphatidylcholine, and NADPH under aerobic conditions, but with the latter cytochrome the reaction has a lower Km and maximal rate.