Hemin mitigates contrast-induced nephropathy by inhibiting ferroptosis via HO-1/Nrf2/GPX4 pathway.
Clin Exp Pharmacol Physiol
; 49(8): 858-870, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35598290
ABSTRACT
Contrast-induced nephropathy (CIN) is a common complication with adverse outcome after iodinated-contrast injection, yet still lacking effective medication. Heme oxygenase-1 (HO-1) has been reported to play an important role against renal injuries. Hemin, a HO-1 inducer and anti-porphyria medicine, may have a promising effect against CIN. In this study, we aim to investigate the effect of hemin on CIN model and the underlying molecular mechanisms in human proximal tubule epithelial cells (HK-2). To mimic a common condition in percutaneous coronary intervention (PCI) patients, CIN was induced by intravenous iopromide in high-fat fed diabetic rats. We found hemin, given right before iopromide, mitigated CIN with enhanced antioxidative capacity and reduced oxidative stress. HK-2 cells insulted by iopromide demonstrated decreased cell vitality and rising reactive oxygen species (ROS), which could also be inhibited by hemin. The effects of hemin involved a key molecule in ferroptosis, glutathione peroxidase (GPX4), whose down-expression by small interfering RNA (siRNA) reversed the effect of hemin on HK-2 cells. Furthermore, hemin's induction of GPX4 involved HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2). Either HO-1 or Nrf2 inhibitor prevented hemin's effect on GPX4 to a comparable extent, and over-expression of Nrf2 increased GPX4 expression. Moreover, intervention of ferroptosis inhibitor liproxstatin-1 also alleviated CIN in vivo. Therefore, we showed hemin mitigated CIN, inhibiting oxidative stress and ferroptosis, by upregulation of GPX4 via activation of HO-1/Nrf2. Hemin, as a clinical medicine, has a translational significance in treating CIN, and anti-ferroptosis is a potential therapeutic strategy for CIN.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Meios de Contraste
/
Células Epiteliais
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Ferroptose
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Fármacos Hematológicos
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Hemina
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Nefropatias
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China