LIPID-PEROXIDATION INDUCED BY ADRIAMYCIN IN LINOLENIC ACID-LOADED CULTURED-HEPATOCYTES

Addition of more than 10 mu M of adriamycin to cultured rat hepatocyte s loaded with alpha-linolenic acid (linolenic acid-loaded hepatocytes) caused marked lipid peroxidation as measured by an accumulation of ma londialdehyde during a 9 kr incubation. After addition of 50 mu M of a driamycin to linolenic acid-loaded hepatocytes, malondialdehyde accumu lation significantly increased at 3 hr. followed by cellular reduced g lutathione decrease and lactate dehydrogenase leakage after 6 hr. Inhi bition of adriamycin-induced lipid peroxidation by addition of N,N'-di phenyl-p-phenylenediamine or alpha-tocopherol both lipid radical scave ngers, or deferoxamine, which is a Fe ion chelator, prevented both glu tathione decrease and lactate dehydrogenase leakage, indicating that l ipid peroxidation caused cellular damage to linolenic acid-loaded hepa tocytes exposed to adriamycin. The effect of SKF 525-A, which is a cyt ochrome P450 inhibitor; on adriamycin-induced lipid peroxidation and o n 7-ethoxycoumarin O-deethylase activity was determined by 6 hr incuba tion of linolenic acid-loaded cells. Addition of SKF 525-A suppressed adriamycin-induced lipid peroxidation comparably with its 7-ethoxycoum arin O-deethylase inhibitory activity These results suggest that cytoc hrome P450 contributes to the one-electron bioreduction of adriamycin into its semiquinone radical in rat hepatocytes.