TY - JOUR
T1 - Renal iron accumulation and oxidative injury with aging
T2 - Effects of treatment with an iron chelator
AU - Bloomer, Steven A.
AU - Brown, Kyle E.
AU - Kregel, Kevin C.
N1 - Funding Information:
This work was supported by a Faculty Development Grant from Penn State University, Abington College (S.A.B.), and National Institutes of Health grant AG-12350 (K.C.K.).
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2020/3/9
Y1 - 2020/3/9
N2 - Dysregulation of iron metabolism in the kidney may contribute to age-related increases in renal oxidative stress and dysfunction. This study assessed the effects of short-term iron chelation on markers of iron status, oxidative stress, inflammation, and autophagy in the kidneys of old rats. Old Fischer 344 rats (24 months) were treated with deferoxamine (DFO; 200 mg/kg, twice daily for 4.5 days); saline-treated young (6 months) and old rats served as controls. Renal nonheme iron was significantly higher in the old rats, with iron localized in the renal cortex. Ferritin levels were elevated in the kidneys of old rats, while expression of several antioxidant enzymes and mitochondrial proteins were reduced and protein carbonyls increased compared to young rats. DFO treatment significantly reduced ferritin levels, and increased transferrin receptor-1 protein, but did not affect nonheme iron content or protein carbonyls, nor did it reverse age-related changes in antioxidant enzymes and mitochondrial proteins. Although short-term DFO treatment did not mitigate the age-related increase in iron content and oxidative damage, this work demonstrates that old rats respond appropriately to DFO, suggesting that optimization of iron chelation regimens could be useful in improving renal homeostasis with aging.
AB - Dysregulation of iron metabolism in the kidney may contribute to age-related increases in renal oxidative stress and dysfunction. This study assessed the effects of short-term iron chelation on markers of iron status, oxidative stress, inflammation, and autophagy in the kidneys of old rats. Old Fischer 344 rats (24 months) were treated with deferoxamine (DFO; 200 mg/kg, twice daily for 4.5 days); saline-treated young (6 months) and old rats served as controls. Renal nonheme iron was significantly higher in the old rats, with iron localized in the renal cortex. Ferritin levels were elevated in the kidneys of old rats, while expression of several antioxidant enzymes and mitochondrial proteins were reduced and protein carbonyls increased compared to young rats. DFO treatment significantly reduced ferritin levels, and increased transferrin receptor-1 protein, but did not affect nonheme iron content or protein carbonyls, nor did it reverse age-related changes in antioxidant enzymes and mitochondrial proteins. Although short-term DFO treatment did not mitigate the age-related increase in iron content and oxidative damage, this work demonstrates that old rats respond appropriately to DFO, suggesting that optimization of iron chelation regimens could be useful in improving renal homeostasis with aging.
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U2 - 10.1093/gerona/glz055
DO - 10.1093/gerona/glz055
M3 - Article
C2 - 30794723
AN - SCOPUS:85074778844
SN - 1079-5006
VL - 75
SP - 680
EP - 684
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 4
ER -