In vivo suppression of stearyl CoA desaturase activity by griseofulvin: evidence against the involvement of lipid peroxidation.

Administration of a diet containing 2.5% (w/w) griseofulvin (GF) resulted in a significant decrease in hepatic microsomal stearyl CoA desaturase activity compared to desaturase activity in microsomes from animals fed a normal rat chow diet. Desaturase activities were 0.66 +/- 0.18 vs 0.16 +/- 0.09 nmoles oleyl CoA formed/min/mg protein for control and GF-fed animals, respectively. Examination of lipid peroxides in microsomes from control and GF-treated rats showed an approximate fivefold higher concentration of lipid peroxides in microsomes from GF-treated rats compared to that from controls. However, when rats were fed a diet containing GF and diphenyl-p-phenylenediamine an inhibitor of lipid peroxidation, stearyl CoA desaturase activity was still similar to that observed with GF alone, even though microsomal lipid peroxides were reduced to nondetectable levels. In vitro stimulation of microsomal lipid peroxidation using ADP-Fe and EDTA-Fe did not result in a significant decrease in desaturase activity. Results of our experiments show that dietary administration of GF results in a marked decrease in stearyl CoA desaturase activity in hepatic microsomes. Although GF feeding stimulates microsomal lipid peroxidation, increase in microsomal peroxidation does not appear to be the mechanism by which GF feeding decreases desaturase activity. GF appears to act by decreasing the terminal desaturase activity.