CROCETIN PROTECTS AGAINST OXIDATIVE DAMAGE IN RAT PRIMARY HEPATOCYTES

Crocetin is a major component in the fruit of Gardenia jaminoides Ellis, a Chinese herbal medicine. Its protective action and mechanism against oxidative damage were investigated. Reactive oxygen species (ROS) were generated enzymatically in the xanthine-xanthine oxidase (X/XO 5 mu M/0.01 u/ml) system and non-enzymatically in the paraquat (PQ 5 mM) system. Both systems increased leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT) in rat primary hepatocytes, but the hepatotoxicity was significantly suppressed on pretreatment with crocetin (10, 20 mu M). Crocetin decreased formation of malondialdehyde (MDA) as an index of lipid peroxidation induced by ROS. The oxyradical generation by X/XO or PQ caused DNA damage evaluated with unscheduled DNA synthesis (UDS) in rat primary hepatocytes. The addition of crocetin decreased genotoxicity evaluated with UDS in both systems. The data showed that crocetin also inhibited the formation of superoxide anion in the X/XO system and bleached the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). The protective action of crocetin operated via quenching of the superoxide anion and/or free radical..