Guan-Hong Lin

Excessive administration of epinephrine and norepinephrine in critically ill patients may trigger a catecholamine storm and contribute to acute kidney injury (AKI) through activation of β-adrenoceptor signaling. Although clinical observations link high-dose catecholamine exposure to increased AKI risk, experimental models and mechanistic studies remain limited. We established a rodent model of combined epinephrine and norepinephrine infusion to investigate the renoprotective effects of subtype-selective β-adrenoceptor blockers. Animals received the β1-selective blockers metoprolol or atenolol, or the β2-selective blocker ICI 118,551. β1-adrenoceptor blockade, particularly with metoprolol, significantly attenuated renal histopathological injury and improved biochemical markers of kidney dysfunction. These protective effects were associated with suppression of ferroptosis-related pathways in the renal cortex. Atenolol partially improved biochemical parameters but did not significantly reduce tubulointerstitial damage, whereas β2-adrenoceptor blockade conferred limited functional benefit despite modest morphological improvement. Collectively, our findings indicate that β1-adrenoceptor activation plays a critical role in catecholamine-induced AKI by promoting ferroptosis. Targeting β1-adrenoceptors, especially with metoprolol, may represent a potential therapeutic strategy for preventing renal injury during catecholamine storms.

Hypoxia during the postnatal period represents a significant risk factor for renal injury in neonates, yet the molecular mechanisms linking oxygen deprivation to kidney damage remain unclear. In this study, we explored whether ferroptosis serves as a key mediator in hypoxia-induced acute kidney injury (AKI). Using a neonatal rat model, we demonstrated that hypoxic exposure disrupts iron homeostasis, leading to iron accumulation and excessive lipid peroxidation in renal tissues. These alterations were associated with marked tubular injury, glomerular damage, and progressive fibrotic remodeling. Importantly, reoxygenation attenuated ferroptosis-related signaling pathways and improved renal structural and functional outcomes, although incomplete recovery was observed in fibrotic changes. Our findings suggest that ferroptosis is not only involved in the initiation of hypoxia-induced renal injury but may also contribute to its progression toward chronic kidney pathology. Targeting ferroptosis and iron metabolism may therefore represent a promising strategy for preventing or treating neonatal hypoxia-related AKI.