Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats
Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the form...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/19/3913 |
| _version_ | 1797477660639625216 |
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| author | Shasta A. McMillen Eric B. Nonnecke Bo Lönnerdal |
| author_facet | Shasta A. McMillen Eric B. Nonnecke Bo Lönnerdal |
| author_sort | Shasta A. McMillen |
| collection | DOAJ |
| description | Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation of reactive oxygen species, alter systemic inflammatory signaling, and/or dysregulate trace mineral metabolism. To better characterize the in vivo effects of excess iron on development, we utilized a pre-weanling rat pup model. Lewis rat litters were culled to eight pups (four males and four females) and randomly assigned to daily supplementation groups receiving either vehicle control (CON; 10% <i>w/v</i> sucrose solution) or ferrous sulfate (FS) iron at one of the following doses: 10, 30, or 90 mg iron/kg body weight—FS-10, FS-30, and FS-90, respectively—from postnatal day (PD) 2 through 9. FS-90 litters, but not FS-30 or FS-10, failed to thrive compared to CON litters and had smaller brains on PD 10. Among the groups, FS-90 liver iron levels were highest, as were white blood cell counts. Compared to CON, circulating MCP-1 and liver zinc were increased in FS-90 pups, whereas liver copper was decreased. Growth defects due to excess FS provision in pre-weanling rats may be related to liver injury, inflammation, and altered trace mineral metabolism. |
| first_indexed | 2024-03-09T21:20:55Z |
| format | Article |
| id | doaj.art-82bef5e8f0e544febeaec5942629c6b5 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T21:20:55Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-82bef5e8f0e544febeaec5942629c6b52023-11-23T21:22:23ZengMDPI AGNutrients2072-66432022-09-011419391310.3390/nu14193913Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling RatsShasta A. McMillen0Eric B. Nonnecke1Bo Lönnerdal2Department of Nutrition, University of California, Davis, CA 95616, USADepartment of Nutrition, University of California, Davis, CA 95616, USADepartment of Nutrition, University of California, Davis, CA 95616, USAIron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation of reactive oxygen species, alter systemic inflammatory signaling, and/or dysregulate trace mineral metabolism. To better characterize the in vivo effects of excess iron on development, we utilized a pre-weanling rat pup model. Lewis rat litters were culled to eight pups (four males and four females) and randomly assigned to daily supplementation groups receiving either vehicle control (CON; 10% <i>w/v</i> sucrose solution) or ferrous sulfate (FS) iron at one of the following doses: 10, 30, or 90 mg iron/kg body weight—FS-10, FS-30, and FS-90, respectively—from postnatal day (PD) 2 through 9. FS-90 litters, but not FS-30 or FS-10, failed to thrive compared to CON litters and had smaller brains on PD 10. Among the groups, FS-90 liver iron levels were highest, as were white blood cell counts. Compared to CON, circulating MCP-1 and liver zinc were increased in FS-90 pups, whereas liver copper was decreased. Growth defects due to excess FS provision in pre-weanling rats may be related to liver injury, inflammation, and altered trace mineral metabolism.https://www.mdpi.com/2072-6643/14/19/3913iron supplementationiron toxicityinfantsrat modeltrace mineral interactionsinflammation |
| spellingShingle | Shasta A. McMillen Eric B. Nonnecke Bo Lönnerdal Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats Nutrients iron supplementation iron toxicity infants rat model trace mineral interactions inflammation |
| title | Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats |
| title_full | Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats |
| title_fullStr | Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats |
| title_full_unstemmed | Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats |
| title_short | Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats |
| title_sort | trace element interactions inflammatory signaling and male sex implicated in reduced growth following excess oral iron supplementation in pre weanling rats |
| topic | iron supplementation iron toxicity infants rat model trace mineral interactions inflammation |
| url | https://www.mdpi.com/2072-6643/14/19/3913 |
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