Smokeless tobacco extract impairs iron homeostasis in rats and human hepatoma,HepG2 cells

Tobacco exposure may alter homeostasis of iron (Fe), one of the most abundant and essential transition metals in the body. In this study, the effect of aqueous extract of smokeless tobacco was evaluated on Fe homeostasis in rats and human hepatoma, HepG2 cells. Our findings suggested that tobacco consumption even at low doses impairs Fe homeostasis leading to Fe deficiency anemia. Significant alterations were noted with respect to hematological parameters and expression patterns of selected intestinal Fe-transporters, Fe-binding proteins, and Fe-regulatory hormone, hepcidin. Impairment in the hepatic and renal antioxidant defense system was also observed in the treated rats. Histopathological studies revealed cirrhosis of liver and goblet cell hyperplasia of small intestine. Further, analysis of hepcidin promoter and its expression along with ferritin (expression and ELISA) in HepG2 cells demonstrated an enhanced expression of both the genes resulting in sequestration of Fe in treated cells, thus indicating systemic Fe deficiency.