Abstract
Oxidative stress is a key component of renal ischemia/reperfusion (I/R) injury. Fucoxanthin (Fx), a marine carotenoid with enhanced antioxidant capacity, acts as a ROS inhibitor in diseases such as ischemic stroke and acute lung injury. We hypothesized that fucoxanthin could attenuate renal I/R-induced oxidative damage. C57BL/6 mice (n = 30) were randomly assigned to sham, IR, IR + DMSO, and IR + Fx (25, 50, and 100 mg/kg) groups. The renal I/R injury was induced by clamping the left kidney nephron tip in mice. Fucoxanthin was injected intraperitoneally 24 hours before surgery. Compared with the IR group, pretreatment with fucoxanthin significantly improved renal dysfunction and tissue structural damage and inhibited ROS levels and apoptosis. Consistent results were observed in HK-2 cells. Besides, we found that renal I/R resulted in decreased expression of Sirt1, Nrf2, and HO-1, while fucoxanthin upregulated the expression of Sirt1, Nrf2, and HO-1. The protective effects of fucoxanthin were significantly reversed by EX527 (a selective inhibitor of Sirt1) or si-Sirt1. In conclusion, our study investigated the protective effect of fucoxanthin against renal I/R injury, and the underlying mechanism may be related to the activation of the Sirt1/Nrf2/HO-1 signaling pathway by fucoxanthin to attenuate oxidative stress-induced apoptosis.
Highlights
Acute kidney injury (AKI) is a common clinical syndrome, usually caused by renal surgery and sepsis, characterized by a sudden decrease in glomerular filtration rate during the initial phase [1]
We found that the expression level of Silent information regulator 1 (Sirt1) protein was significantly decreased when HK-2 cells were exposed to H/R compared to the control group, and the expression levels of Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream HO-1 were significantly decreased
We found that fucoxanthin could activate the Sirt1/Nrf2/HO-1 signaling pathway after I/R injury or H/R injury and that the protective effect of fucoxanthin could be reversed using pharmacological inhibitors of Sirt1 or si-RNA
Summary
Acute kidney injury (AKI) is a common clinical syndrome, usually caused by renal surgery and sepsis, characterized by a sudden decrease in glomerular filtration rate during the initial phase [1]. AKI is associated with adverse clinical outcomes, including chronic kidney disease [2] and increased mortality [3]. Mitochondria are severely damaged in tissues, and the function of complexes I and III, which maintain mitochondrial function, is altered, leading to ROS production [8, 9]. Reactivation of aerobic metabolism and hyperoxia alters the function of mitochondrial complexes, leading to increased production of ROS. With the increased morbidity and mortality of renal I/R injury, there is an urgent need to find new therapeutic targets and develop new treatment approaches
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