Protective Effects of Tetrahydrocurcumin and Curcumin against Doxorubicin and Cadmium-Induced Cytotoxicity in Chang Liver Cells

Purpose: To investigate the cytoprotective effect of tetrahydrocurcumin, (THC) and curcumin (CUR) on cytotoxicity induced by doxorubicin and cadmium in Chang liver cells.
Methods: Cytotoxicity was determined by sulforhodamine B assay. The expression of nuclear factorerythroid- 2-related factor 2 (Nrf2) Nrf2 regulated cytoprotecetive enzymes, glutamylcysteine ligase catalytic subunit (GCLC) and NADP (H): quinone oxidoreductase1 (NQO1) was determined by Western blot analysis. Nuclear translocation of Nrf-2 was analyzed by immunofluorescence method. The level of superoxide formation was assayed by chemiluminescence method.
Results: Treatment with THC or CUR significantly induced GCLC and NQO1 expression and the nuclear translocation of Nrf2. Exposure to doxorubicin (DOX) or Cd for 24 h induced cell death of about 50 %. However, pre-treatment with THC or CUR (1 or 6 μM) for 24 h significantly increased cell survival to 80 or 90 %, respectively (p < 0.05). Similar pre-treatment with THC or CUR significantly protected against Cd-induced cell death by a level of 80 and 85 %, respectively (p < 0.05). The cytoprotective effect of these compounds was associated with suppressed DOX- and Cd-induced superoxide formation and induction of GCLC and NQO1 expression.
Conclusions: THC mediates its effects by activation of Nrf2 and its regulated enzymes, GCLC and NQO1. Induction of GCLC, NQO1 protein expression and suppression of superoxide are associated with the cytoprotective effect.

Keywords
Chang hepatocyte; Curcumin; Tetrahydrocurcumin; Cytoprotection; Doxorubicin; Cadmium