MECHANISMS OF ANTICARCINOGENIC PROPERTIES OF CURCUMIN - THE EFFECT OFCURCUMIN ON GLUTATHIONE LINKED DETOXIFICATION ENZYMES IN RAT-LIVER

Curcumin, an antioxidant isolated from turmeric (curcuma longa), has b een shown to attenuate chemical carcinogenesis in rodents. Previous st udies have shown that curcumin causes an increase in glutathione S-tra nsferase (GST) activity in rodent liver which may contribute to its an ti-cancer and anti-inflammatory activities. Since the effects of curcu min on specific GST isozymes and other glutathione (GSH)-linked enzyme s are incompletely defined, we have examined in the present studies th e effect of curcumin on hepatic non-protein sulfhydryls and GSH-linked enzymes in male Sprague-Dawley rats. When rats were fed curcumin at d oses from 1 to 500 mg kg(-1) body weight daily for 14 days, the induct ion of hepatic GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was found to be biphasic, with maximal induction of about 1.5 fold at the 25 to 50 mg kg(-1) body weight dosage, At higher doses, a decreas e was observed in the activity and in the rats treated with 500 mg kg( -1) curcumin this activity was below the levels observed in controls. In contrast, GST activity towards 4-hydroxynonenal (4-HNE) increased i n a saturable, dose dependent manner. Western-blot analyses of liver c ytosols revealed that curcumin caused a dose dependent induction of rG ST 8-8, an isozyme which is known to display the highest activity towa rds 4-HNE, a highly toxic product of lipid peroxidation. Glutathione p eroxidase (GPx) activity towards cumene hydroperoxide in liver homogen ate was also found to be increased in a saturable manner with respect to curcumin dose. Our results suggest that induction of enzymes involv ed in the detoxification of the electrophilic products of lipid peroxi dation may contribute to the anti-inflammatory and anticancer activiti es of curcumin. (C) 1998 Elsevier Science Ltd. All rights reserved.