Dual action of vitamin C in iron supplement therapeutics for iron deficiency anemia: prevention of liver damage induced by iron overload,Food & Function

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Dual action of vitamin C in iron supplement therapeutics for iron deficiency anemia: prevention of liver damage induced by iron overload
Food & Function ( IF 5.1 ) Pub Date : 2018-09-18 00:00:00 , DOI: 10.1039/c7fo02057k
Huan He _{1,

2,

3,

4,

5} , Yang Qiao _{3,

4,

5,

6} , Zeyu Zhang _{3,

4,

5,

6} , Zelong Wu _{3,

4,

5,

6} , Dan Liu _{3,

4,

5,

6} , Zhangping Liao _{3,

4,

5,

6} , Dong Yin _{3,

4,

7,

8} , Ming He _{1,

2,

3,

4}

Affiliation

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.

中文翻译：

维生素C在铁补充剂治疗铁缺乏性贫血中的双重作用：预防铁超负荷引起的肝损害

维生素C是一种出色的还原剂，有助于增加缺铁性贫血中可吸收的亚铁。作为有效的抗氧化剂，维生素C是否对铁过多引起的肝损害具有保护作用，线粒体是否是上述作用的目标效应物，仍是未知的。在这项研究中，将48只小鼠随机分为对照组，铁超载组，TAU治疗+铁超载组和维生素C治疗+铁超载组，每组12只。用补充二茂铁形式的铁的颗粒饲料给小鼠喂食4个月。日粮中的铁比在90天内保持在0.2％（w / w），然后在剩余30天中保持在0.4％（w / w）。此外，2 g kg ^-1维生素C和20 mg kg ^-1在第6周和整个实验过程中，每天通过口服强饲法施用TAU，然后进行铁超负荷施用。我们通过评估肝脏重量与体重比（LW / BW），血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的活性以及组织学变化，研究了维生素C对肝脏损害的保护作用。此外，对酶和非酶抗氧化剂，活性氧（ROS）生成，线粒体肿胀和线粒体膜电位（MMP）进行了评估，以阐明维生素C的抗氧化作用。小鼠诱导铁过载经由抗氧化作用，而未观察到对铁吸收的显着影响。维生素C靶向线粒体，防止线粒体肿胀，MMP耗散和ROS破裂，从而抑制肝细胞凋亡。总体而言，我们的研究结果表明，维生素C在补铁疗法中用于铁缺乏症贫血的“双重作用”，可促进铁的吸收，预防铁缺乏症，并防止治疗期间因铁摄入过多而引起肝脏损害。

更新日期：2018-09-18

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