Effects of curcumin supplementation on iron overload and liver cancer in a mouse model of hereditary hemochromatosis (829.8)

Abstract

Curcumin, a key bioactive component of the dietary spice turmeric, is an antioxidant iron chelator with cancer prevention potential. The aim of this study was to investigate curcumin and turmeric for iron depletion and chemoprevention of diethylnitrosamine (DEN)‐induced liver cancer in a mouse model of hemochromatosis. C3H/HeJ wild type and hfe ‐/‐ male mice were given a single IP injection of DEN at 5 weeks of age and then fed diets containing 40 ppm iron, +/‐ 2% curcumin or 5% turmeric (≍0.2% curcumin). At 36 weeks of age the hfe ‐/‐ mice showed 3‐fold higher levels of liver iron but similar incidence of DEN‐induced cancer vs.wild type. Dietary curcumin did not alter body weights, liver iron, or incidence of cancer (≍77% in all hfe ‐/‐ groups). However the number of liver tumors per animal were increased 2.8x in the curcumin group (p<0.01) and 2.3x in the turmeric group (p<0.05). Liver/body weight ratios increased in both groups (p<0.001). There was no effect of diet on oxidative damage (TBARS) in tumor‐free liver tissue. Western blots suggested increased liver redox defenses (GST‐α and heme oxygenase‐1) in animals fed turmeric. We conclude that addition of curcumin near the maximum achievable in the diet was not effective in decreasing iron overload in this mouse model of hemochromatosis. High levels of dietary curcumin and turmeric appeared to increase, rather than protect against, the hepatocarcinogenic effects of DEN.Grant Funding Source: NIH #AT003448