Jeon You Hyun, Oh Eun-Joo, Oh Se-Hyun, Lim Jeong-Hoon, Jung Hee-Yeon, Choi Ji-Young, Cho Jang-Hee, Park Sun-Hee, Kim Yong-Lim, Kim Chan-Duck
Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea.
Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea.
Biomolecules. 2024 Nov 27;14(12):1522. doi: 10.3390/biom14121522.
Destabilization of heme proteins is recognized to play a role in acute kidney injury (AKI). Hemopexin (Hpx), known for its role in binding heme, mitigates free heme toxicity. Despite this, the potential adverse effects of Hpx deposition in kidney tissues and its impact on kidney function are not fully understood. Deferoxamine (DFO) chelates iron released from heme and mitigates associated kidney damage. Therefore, this study aimed to evaluate whether Hpx contributes to kidney injury in an ischemia-reperfusion injury (IRI) induced AKI model and to investigate if DFO could alleviate this damage. Mice were categorized into five groups: Sham-Vehicle, Sham-Hpx, IRI-Vehicle, IRI-Hpx, and IRI-Hpx-DFO. Decline in kidney function was observed exclusively in the IRI group, independent of Hpx injection. Serum Hpx levels remained comparable across all groups, and administration of Hpx did not alter serum Hpx levels or kidney function after 24 hours. Although increased Hpx deposition in kidneys was noted in both the IRI and Hpx groups, this accumulation did not correlate with impaired kidney function. Additionally, DFO did not exhibit a protective effect against kidney injury. In summary, Hpx does not directly induce kidney injury and cannot be considered a biomarker for kidney damage caused by IRI.
血红素蛋白的不稳定被认为在急性肾损伤（AKI）中起作用。血红素结合蛋白（Hpx）以其结合血红素的作用而闻名，可减轻游离血红素的毒性。尽管如此，Hpx在肾组织中沉积的潜在不良影响及其对肾功能的影响尚未完全了解。去铁胺（DFO）螯合从血红素释放的铁并减轻相关的肾损伤。因此，本研究旨在评估Hpx是否在缺血再灌注损伤（IRI）诱导的AKI模型中导致肾损伤，并研究DFO是否可以减轻这种损伤。将小鼠分为五组：假手术-载体组、假手术-Hpx组、IRI-载体组、IRI-Hpx组和IRI-Hpx-DFO组。仅在IRI组中观察到肾功能下降，与是否注射Hpx无关。所有组的血清Hpx水平保持相当，并且注射Hpx后24小时血清Hpx水平和肾功能均未改变。虽然在IRI组和Hpx组中均观察到肾脏中Hpx沉积增加，但这种积累与肾功能受损无关。此外，DFO对肾损伤未表现出保护作用。总之，Hpx不会直接诱导肾损伤，不能被视为IRI引起的肾损伤的生物标志物。
