Dual action of vitamin C in iron supplement therapeutics for iron deficiency anemia: prevention of liver damage induced by iron overload.
Food Funct. 2018 Oct 17 ;9(10):5390-5401. PMID: 30272083
Vitamin C, an excellent reducing agent, aids in increasing absorbable ferrous iron in iron deficiency anemia. As an efficient antioxidant, it is still unknown whether vitamin C exerts protective effects against liver damage caused by iron excess and whether mitochondria are the target effectors of the above effects. In this study, 48 mice were randomly divided into a control group, iron-overload group, TAU-treated + iron-overload group and vitamin C-treated + iron-overload group with 12 mice per group. The mice were fed 4 months on pellet diets supplemented with iron in the form of ferrocene. The iron ratio in the diet was maintained at 0.2% (w/w) for 90 days and then 0.4% (w/w) for the remaining 30 days. Furthermore, 2 g kg-1 vitamin C and 20 mg kg-1 TAU were administered daily by oral gavage prior to iron-overload administration at 6 weeks and throughout the course of the experiments. We investigated the protective effects of vitamin C against liver damage by assessing the liver weight to body weight ratio (LW/BW), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and histological changes. In addition, enzymatic and non-enzymatic antioxidants, reactive oxygen species (ROS) generation, mitochondrial swelling, and mitochondrial membrane potential (MMP) were evaluated to clarify the antioxidant effects of vitamin C. We found that vitamin C significantly attenuated impaired liver function in mice induced by iron overload via antioxidation, whereas no significant effect on iron uptake was observed. Vitamin C targeted the mitochondria, preventing mitochondrial swelling, MMP dissipation, and ROS burst, thus inhibiting hepatic apoptosis. Collectively, our results suggest that vitamin C acts as a"double agent"in iron supplementation therapy for iron deficiency anemia, boosting iron absorption for preventing iron deficiency and preventing liver damage due to excessive iron intake during treatment.