Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis.

Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 µM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc- inhibitor erastin (10 µM), and the effect of the 40 µM dose of PD was more obvious than that of ferrostatin-1 (1 µM) and deferoxamine (DFO, 100 µM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc--GSH-GPx4 axis and iron metabolism.

Treatment of retinal vein occlusion in rabbits with traditional Chinese medicine Fufang XueShuan Tong.

BACKGROUND: Retinal vein occlusion (RVO) is one of the most common causes of visual loss. Many approaches have been tried to treat central retinal vein occlusion (CRVO), and branch retinal vein occlusion (BRVO) with various results. However, there is no defined protocol and limited evidence to support the interventions currently used. The aim of this study was to assess the efficacy of the traditional Chinese medicine Fufang XueShuan Tong (FXST) in treating experimentally created RVO. METHODS: RVO model was first induced in forty-four pigmented rabbits through photocoagulation following injection of rose Bengal. The rabbits were divided into four groups based on the dose of FXST administered (212 mg/kg, 424 mg/kg, 848 mg/kg and control group). The rabbits were observed for four weeks after the procedure, using color fundus photography, fundus fluorescein angiography and electroretinogram examination. Vascular endothelial growth factor (VEGF), interleukin-6 and nitric oxide (NO) levels in the vitreous and histopathologic evaluation were monitored. RESULTS: The obstructed vessels in the treatment groups reopened or anastomosed faster than those in the control group (P < 0.05). The amplitude of maximum b wave and the oscillatory potential were significantly higher in the treatment groups than in the control group (P < 0.01). At both two weeks and four weeks, VEGF and IL-6 levels in the vitreous were significantly decreased in the treatment groups (P < 0.01), while NO levels were significantly elevated (P < 0.01). At the same time, histopathologic evaluation showed different retinal neuroepithelium structures in the different groups. Immunoreactivity of VEGF was greater in the control group than in the treatment groups. CONCLUSION: FXST was helpful in reconstructing retinal vessels in the RVO model, protecting retinal structures and improving visual function, and could inhibit the neovascular factor.