Dual action of vitamin C in iron supplement therapeutics for iron deficiency anemia: prevention of liver damage induced by iron overload
Dual action of vitamin C in iron supplement therapeutics for iron deficiency anemia: prevention of liver damage induced by iron overload
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维生素C在缺铁性贫血补铁疗法中的双重作用：预防铁过载引起的肝损伤
DOI：
10.1039/c7fo02057k
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发表时间：
2018-10-01
期刊：
影响因子：
6.1
通讯作者：
He, Ming
中科院分区：
文献类型：
--
作者：
He, Huan;Qiao, Yang;He, Ming
维生素C是一种很好的还原剂，有助于增加缺铁性贫血中可吸收的亚铁。作为一种有效的抗氧化剂，维生素C是否对铁过量引起的肝损伤具有保护作用以及线粒体是否是上述作用的靶效应器仍然是未知的。将48只小鼠随机分为对照组、铁负荷组、TAU+铁负荷组和维生素C+铁负荷组，每组12只。这些小鼠用补充有二茂铁形式的铁的颗粒饲料喂养4个月。饲料中的铁比率维持在0.2%（w/w）持续90天，然后在剩余的30天中维持在0.4%（w/w）。此外，在第6周和整个实验过程中，在铁过载给药前，每天经口灌胃给予2 g/kg（-1）维生素C和20 mg/kg（-1）TAU。我们通过评估肝脏重量/体重比（LW/BW）、血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性以及组织学变化来研究维生素C对肝损伤的保护作用。此外，还评价了酶促和非酶促抗氧化剂、活性氧（ROS）生成、线粒体肿胀和线粒体膜电位（MMP），以阐明维生素C的抗氧化作用。我们发现维生素C通过抗氧化作用显著减轻了铁过载引起的小鼠肝功能损害，而对铁的摄取没有显著影响。维生素C靶向线粒体，防止线粒体肿胀，MMP耗散和ROS爆发，从而抑制肝细胞凋亡。总的来说，我们的研究结果表明，维生素C在缺铁性贫血的补铁治疗中起着双重作用，促进铁的吸收，以防止缺铁，并防止治疗期间因铁摄入过量而导致的肝损伤。
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.