EFFECTS OF A BENZIMIDAZOLE COMPOUND ON MONOOXYGENASE ACTIVITIES

A retinoid-type benzimidazole compound (benzimidazole-tetranaphthalene , BITN) was synthesized and its effects on hepatic cytochrome P450 (CY P) dependent ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) enzyme activities were determined in rats in vitr o. In vitro addition of BITN in 10(-3) M concentration to the reaction medium caused inhibitions in EROD (94%) and PROD (82%) activities. Wi th the same concentration (10(-3) M) all-trans-retinoic acid (RA) was able to inhibit EROD activity 65% and PROD activity 59% whereas buthyl ated hydroxytoluen (BHT) inhibited EROD and PROD activities 73% and 62 %, respectively. The specific inhibitors of EROD activity (caffeine) a nd PROD activity (SKF 525A) at 10(-3) M concentration inhibited the co rresponding enzymes 33% and 77%, respectively. Thus, these results rev eal that the BITN has a stronger inhibitory effect than RA, BHT, caffe ine and SKF 525 A on the enzyme activities. Since these enzymes (EROD, CYP 1A1/2 and PROD, CYP2B1) activate polycyclic hydrocarbons, aromati c amines and aliphatic halogenated hydrocarbons to their ultimate muta genic or carcinogenic forms, and are effective in producing reactive o xygen species such as superoxide, hydroxyl radical and hydrogen peroxi de, the new compound, BITN, appears to have a greater anticarcinogenic and antioxidant potential than RA and BHT.