An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis
The liver is easily injured by exogenous chemicals through reactive oxygen species (ROS), which lead to ferroptosis, a ROS-dependent programmed cell death characterized by iron accumulation and lipid peroxidation. However, whether iron restriction has a positive role in chemicals-induced liver injur...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Current Research in Food Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665927122002040 |
| _version_ | 1811188506899251200 |
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| author | Zelong Gao Dongyao Wang Hongwei Zhang Jianxin Yang Min Li Hongtao Lu Hui Shen Yuxiao Tang |
| author_facet | Zelong Gao Dongyao Wang Hongwei Zhang Jianxin Yang Min Li Hongtao Lu Hui Shen Yuxiao Tang |
| author_sort | Zelong Gao |
| collection | DOAJ |
| description | The liver is easily injured by exogenous chemicals through reactive oxygen species (ROS), which lead to ferroptosis, a ROS-dependent programmed cell death characterized by iron accumulation and lipid peroxidation. However, whether iron restriction has a positive role in chemicals-induced liver injuries is unknown. The present study investigated the effects of an iron-deficient diet on liver injuries induced by alcohol or diethylnitrosamine (DEN). Mice were fed an iron-deficient diet for four weeks, then treated with three doses of alcohol (5 g/kg, 24 h interval, gavage) to mimic mild liver injury or five doses of DEN (50 mg/kg, 24 h interval, i. p.) to mimic severe liver failure. The results showed that mice were iron-deficient after four weeks of feeding. Interestingly, as evaluated by H&E staining of liver slices, liver/body weight ratio, serum ALT and AST, iron deficiency significantly alleviated liver injuries triggered by alcohol or DEN. The activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), and the expression of CYP2E1 were increased by iron deficiency. Mechanistically, iron deficiency prevented the decrease of glutathione peroxidase 4 (GPX4), which eliminated malondialdehyde (MDA) by utilizing glutathione (GSH). In summary, alcohol- or DEN-induced liver injuries were mitigated by the iron-deficient diet by inhibiting ferroptosis, which might be a promising measure for preventing liver injuries induced by alcohol, DEN, or other exogenous chemicals. |
| first_indexed | 2024-04-11T14:21:03Z |
| format | Article |
| id | doaj.art-487c2ed4aeb34bdc8d27fc3141725ad1 |
| institution | Directory Open Access Journal |
| issn | 2665-9271 |
| language | English |
| last_indexed | 2024-04-11T14:21:03Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Food Science |
| spelling | doaj.art-487c2ed4aeb34bdc8d27fc3141725ad12022-12-22T04:19:04ZengElsevierCurrent Research in Food Science2665-92712022-01-01521712177An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosisZelong Gao0Dongyao Wang1Hongwei Zhang2Jianxin Yang3Min Li4Hongtao Lu5Hui Shen6Yuxiao Tang7Department of Nutrition, Second Military Medical University, Shanghai, ChinaSchool of Pharmacy, Second Military Medical University, Shanghai, ChinaDepartment of Nutrition, Second Military Medical University, Shanghai, China; Department of Clinical Nutrition, Zhumadian Second People's Hospital, Henan, ChinaDepartment of Nutrition, Second Military Medical University, Shanghai, ChinaDepartment of Nutrition, Second Military Medical University, Shanghai, ChinaDepartment of Nutrition, Second Military Medical University, Shanghai, ChinaDepartment of Nutrition, Second Military Medical University, Shanghai, China; Corresponding author.Department of Nutrition, Second Military Medical University, Shanghai, China; Corresponding author.The liver is easily injured by exogenous chemicals through reactive oxygen species (ROS), which lead to ferroptosis, a ROS-dependent programmed cell death characterized by iron accumulation and lipid peroxidation. However, whether iron restriction has a positive role in chemicals-induced liver injuries is unknown. The present study investigated the effects of an iron-deficient diet on liver injuries induced by alcohol or diethylnitrosamine (DEN). Mice were fed an iron-deficient diet for four weeks, then treated with three doses of alcohol (5 g/kg, 24 h interval, gavage) to mimic mild liver injury or five doses of DEN (50 mg/kg, 24 h interval, i. p.) to mimic severe liver failure. The results showed that mice were iron-deficient after four weeks of feeding. Interestingly, as evaluated by H&E staining of liver slices, liver/body weight ratio, serum ALT and AST, iron deficiency significantly alleviated liver injuries triggered by alcohol or DEN. The activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), and the expression of CYP2E1 were increased by iron deficiency. Mechanistically, iron deficiency prevented the decrease of glutathione peroxidase 4 (GPX4), which eliminated malondialdehyde (MDA) by utilizing glutathione (GSH). In summary, alcohol- or DEN-induced liver injuries were mitigated by the iron-deficient diet by inhibiting ferroptosis, which might be a promising measure for preventing liver injuries induced by alcohol, DEN, or other exogenous chemicals.http://www.sciencedirect.com/science/article/pii/S2665927122002040Iron deficiencyLiver injuryAlcoholDENFerroptosis |
| spellingShingle | Zelong Gao Dongyao Wang Hongwei Zhang Jianxin Yang Min Li Hongtao Lu Hui Shen Yuxiao Tang An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis Current Research in Food Science Iron deficiency Liver injury Alcohol DEN Ferroptosis |
| title | An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis |
| title_full | An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis |
| title_fullStr | An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis |
| title_full_unstemmed | An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis |
| title_short | An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis |
| title_sort | iron deficient diet prevents alcohol or diethylnitrosamine induced acute hepatotoxicity in mice by inhibiting ferroptosis |
| topic | Iron deficiency Liver injury Alcohol DEN Ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2665927122002040 |
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