Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver

Int J Biochem Cell Biol. 1998 Apr;30(4):445-56. doi: 10.1016/s1357-2725(98)00015-6.

Abstract

Curcumin, an antioxidant isolated from turmeric (curcuma longa), has been shown to attenuate chemical carcinogenesis in rodents. Previous studies have shown that curcumin causes an increase in glutathione S-transferase (GST) activity in rodent liver which may contribute to its anti-cancer and anti-inflammatory activities. Since the effects of curcumin on specific GST isozymes and other glutathione (GSH)-linked enzymes are incompletely defined, we have examined in the present studies the effect of curcumin on hepatic non-protein sulfhydryls and GSH-linked enzymes in male Sprague-Dawley rats. When rats were fed curcumin at doses from 1 to 500 mg kg-1 body weight daily for 14 days, the induction 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 decrease 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 in a saturable, dose dependent manner. Western-blot analyses of liver cytosols revealed that curcumin caused a dose dependent induction of rGST 8-8, an isozyme which is known to display the highest activity towards 4-HNE, a highly toxic product of lipid peroxidation. Glutathione peroxidase (GPx) activity towards cumene hydroperoxide in liver homogenate was also found to be increased in a saturable manner with respect to curcumin dose. Our results suggest that induction of enzymes involved in the detoxification of the electrophilic products of lipid peroxidation may contribute to the anti-inflammatory and anti-cancer activities of curcumin.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Antineoplastic Agents / administration & dosage*
  • Antioxidants / administration & dosage
  • Curcumin / administration & dosage*
  • Enzyme Induction / drug effects
  • Glutathione / metabolism*
  • Glutathione Transferase / drug effects
  • Glutathione Transferase / metabolism*
  • Lipid Peroxidation / drug effects
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Antioxidants
  • Glutathione Transferase
  • Glutathione
  • Curcumin