A STUDY ON THE ANTIOXIDANT CAPACITIES OF SOME BENZIMIDAZOLES IN RAT-TISSUES

Seven benzimidazole compounds were synthesized and their in vitro effe cts on rat liver, lung and kidney microsomal NADPH-dependent lipid per oxidation (LP) levels were determined. The significant decrease in mal e rat liver microsomal LP level was noted only by the compound 4 at 10 (-4) M (20%) and 10(-3) M (40%) concentrations whereas the other compo unds were ineffective. In lung, only the compound 6 at 10(-4) M concen tration exhibited significant alteration, i.e. 56% increase, in LP lev el. In kidney, however, apart from the compound 4, all the compounds i ncreased LP level(35-52%) significantly. The classical antioxidant, bu tylated hydroxy toluene (BHT): at 10(-4) M concentration, significantl y decreased LP level about 70%, in all the tissues studied. To clarify the effects of compounds 4 and 6 on LP, the responses of some CYPs, w hich are active in producing reactive oxygen species, to these compoun ds were also investigated. The compound 4 at 10(-4) and 10(-3) M conce ntrations inhibited the hepatic microsomal ethoxyresorufin O-deethylas e (EROD) (37 and 65%,) and pentoxyresorufin O-depenthylase (PROD) (14 and 62%) enzyme activities significantly. However, it did not alter th e hepatic microsomal NADPH-cytochrome P450-reductase activity. BHT, at 10(-3) M concentration, significantly inhibited hepatic microsomal ER OD (73%), PROD (62%) and NADPH-cytochrome P450 reductase (17%) enzyme activities. Caffeine (10(-3) M) and SKF 525A (10(-3) M), which are spe cific inhibitors of EROD and PROD enzyme activities, significantly dec reased the enzyme activities 33 and 77%, respectively. Caffeine was un able to alter hepatic microsomal NADPH-cytochrome P450 reductase enzym e activity whereas SKF 525A significantly inhibited(80%) of it. In lun g and kidney, the compound 6 at 10(-4) M concentration significantly i ncreased EROD (44 and 19%) and PROD (103 and 86%) enzyme activities. H owever, the elevation of PROD enzyme activity in both tissues was obse rved to be more pronounced than that of EROD enzyme activity. This com pound was ineffective on lung and kidney microsomal P450-reductase enz yme activity. These results reveal that the synthesized benzimidazoles have variable tissue dependent in vitro effects on LP due to their di stinct effects on CYP activities but not on NADPH-cytochrome P450 redu ctase activity in rats. (C) 1998 Elsevier Science Ireland Ltd. All rig hts reserved.