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.

中文翻译：

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肾脏中铁的积累和衰老引起的氧化损伤：铁螯合剂治疗的效果

肾脏中铁代谢的失调可能导致与年龄相关的肾脏氧化应激和功能障碍的增加。这项研究评估了短期铁螯合对老年大鼠肾脏中铁状态，氧化应激，炎症和自噬标志物的影响。用去铁胺（DFO； 200 mg / kg，每天两次，连续4.5天）治疗Fischer 344龄老大鼠（24个月）；盐水处理的幼鼠（6个月）和老年大鼠作为对照。肾非血红素铁在老年大鼠中明显更高，铁位于肾皮质。与年轻大鼠相比，老年大鼠肾脏中的铁蛋白水平升高，而几种抗氧化酶和线粒体蛋白的表达降低，蛋白羰基的含量增加。DFO处理可显着降低铁蛋白水平，和增加转铁蛋白受体1蛋白，但不影响非血红素铁含量或蛋白羰基，也不能逆转与年龄相关的抗氧化酶和线粒体蛋白变化。尽管短期DFO治疗不能减轻与年龄相关的铁含量和氧化损伤的增加，但这项工作表明，老年大鼠对DFO有适当的反应，这表明优化铁螯合方案可改善衰老引起的肾脏稳态。