Dual effect of hemin on renal ischemia-reperfusion injury

Heme oxygenase-1 (HO-1) cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-induced cytokine storm syndrome

“…Due to its dual effect, hemin should be administrated on the onset of respiratory symptoms to prevent ARDS and subsequent overloaded ICU. Hence, we do not recommend hemin use in case of established ARDS because it might worsen the disease based on experimental data [29] .…”

“…hemin preconditioning) [20] , [21] . However, hemin does not protect kidney and even worsened renal insult when acute kidney injury is already established [29] . Hemin may therefore have a dual effect, protective or deleterious, depending on the timing of its administration.…”

New insights into the role of heme oxygenase-1 in acute kidney injury

“…Timing, dose, and context determine whether prior injury promotes preconditioning or exacerbates injury. For example, administering hemin to mice after bilateral IRI worsens renal damage and oxidative stress [23]. However, hemin administration prior to IRI, in addition to hemin administration post-IRI, protects against AKI.…”

Heme-Oxygenase and Kidney Transplantation: A Potential for Target Therapy?

“…Tullius et al [ 46 ] demonstrated that pre-treatment of donor rats with cobalt protoporphyrin (CoPP) resulted in high HO-1 mRNA: after 24 weeks, a significant reduction of proteinuria was associated with HO-1 induction, and about half of CoPP-treated renal allografts with an ischemic period of <32 h survived, and this beneficial effect was observed even when the ischemic period was prolonged up to 44 h. In contrast, grafts without CoPP treatment never started to function when ischemia was prolonged for >12 h. Similar results were reported by Holzen et al [ 47 ], who reported a significant improvement of graft microcirculation, with significant enlargement of the vascular diameter and an increase of the capillary flow when donor rats were pre-treated with the HO-1 inductor hemin. However, Rossi et al [ 48 ] demonstrated that treatment with hemin after renal ischemia is associated with significant renal damage and oxidative stress, and a higher dose of hemin is associated with more severe IRI-induced AKI in a dose-dependent relation. In contrast, pre-treatment of donor rats with hemin resulted in less renal damage and oxidative stress, suggesting that HO-1 induction by hemin may have a dual effect, depending on the time of stimulation [ 48 ].…”

“…However, Rossi et al [ 48 ] demonstrated that treatment with hemin after renal ischemia is associated with significant renal damage and oxidative stress, and a higher dose of hemin is associated with more severe IRI-induced AKI in a dose-dependent relation. In contrast, pre-treatment of donor rats with hemin resulted in less renal damage and oxidative stress, suggesting that HO-1 induction by hemin may have a dual effect, depending on the time of stimulation [ 48 ].…”