Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Zhou, Lu; Yu, Peng; Wang, Tingting; Du, Yiwei; Chen, Yang; Li, Zhen; He, Manlin; Feng, Lan; Li, Huirong; Han, Xiao; Ma, Heng; Liu, Hongbao

doi:10.1155/2022/9947191

Cited by 37 publications

(31 citation statements)

References 60 publications

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“…Recently, PD has been found to protect septic myocardial injury by promoting SIRT6-activated autophagy [19]. Our previous studies confirmed the renal protective effect of PD through antioxidative stress and antiferroptosis in I/R-induced AKI (I/R-AKI) and CP-AKI [4,9,11]. Based on the above evidence, we hypothesized that PD may attenuate CP-AKI through SIRT6-mediated autophagy.…”

Section: Introductionsupporting

confidence: 59%

“…PD has also been verified to play a nephroprotective role by regulating autophagy in sepsis-induced AKI [5,6] and diabetic nephropathy [25]. In our last study, PD can alleviate CP-AKI by inhibiting ferroptosis [4], but whether autophagy is involved in the nephroprotection of PD on CP-AKI has not been reported yet.…”

Section: Introductionmentioning

confidence: 82%

“…Polydatin (PD, C 20 H 22 O 8 ), a glucoside of resveratrol, known as a natural active ingredient extracted from Polygonum cuspidatum Sieb. et Zucc., is used for both medication and food, which plays a multitarget protective role in AKI by antiapoptosis, anti-inflammation, antioxidative stress, antiferroptosis, and regulation of autophagy [4][5][6][7][8][9][10][11][12]. What is more, PD has also been proved to play an antitumor effect by inhibiting cell viability, migration, and invasion of different tumor cells [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury via SIRT6-Mediated Autophagy Activation

Zhou

et al. 2022

Oxidative Medicine and Cellular Longevity

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In the treatment of malignant tumors, the effectiveness of cisplatin (CP) is limited by its nephrotoxicity, leading to cisplatininduced acute kidney injury (CP-AKI). Polydatin (PD) has been demonstrated to regulate autophagy in tumors, sepsis, and diabetes. We have recently confirmed that PD attenuated CP-AKI by inhibiting ferroptosis, but it is not clear whether PD can regulate autophagy to protect from CP-AKI. The purpose of this study was to investigate the effect of PD on autophagy in CPtreated HK-2 cells and CP-AKI mouse models, exploring the role of sirtuin 6 (SIRT6) upregulated by PD. In this study, the blocking of autophagy flux was observed in both CP-treated HK-2 cells in vitro and CP-AKI mouse models in vivo, whereas this blocking was reversed by PD, which was characterized by the increase of autophagy microtubule-associated protein light chain 3 II expression and autophagolysosome/autophagosome ratio and the decrease of p62 expression. Furthermore, PD also significantly increased the expression of SIRT6 in vivo and in vitro. The protective effect of PD manifested by the stimulating of autophagy flux, with the reducing of inflammatory response and oxidative stress, which included downregulation of tumor necrosis factor-α and interleukin-1β, decreased activity of myeloperoxidase and content of malondialdehyde, and increased activity of superoxide dismutase and level of glutathione, both in vivo and in vitro, was reversed by either inhibition of autophagy flux by chloroquine or downregulation of SIRT6 by OSS-128167. Taken together, the present findings provide the first evidence demonstrating that PD exhibited nephroprotective effects on CP-AKI by restoring SIRT6-mediated autophagy flux mechanisms.

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Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury via SIRT6-Mediated Autophagy Activation

Zhou

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Lu et al reported that Ras homolog enriched in brain could relieve cisplatin-induced AKI by maintaining mitochondrial homeostasis ( Lu et al, 2020 ). Zhou et al recently reported that polydatin enabled to attenuate the cell ferroptosis in cisplatin-induced AKI via regulating system Xc−/GSH/GPX4 pathway and inhibiting iron metabolism disorders ( Zhou et al, 2022 ). Deng et al found Se/Albumin nanoparticles could alleviate cisplatin-induced AKI by inhibiting ferroptosis with a decrease of superoxide dismutase, and up-regulation of GSH and GPX4 ( Deng et al, 2022 ).…”

Section: Ferroptosis Is Involved In the Development Of Akimentioning

confidence: 99%

Ferroptosis and Acute Kidney Injury (AKI): Molecular Mechanisms and Therapeutic Potentials

Feng

Qiao

et al. 2022

Front. Pharmacol.

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Acute kidney injury (AKI), a common and serious clinical kidney syndrome with high incidence and mortality, is caused by multiple pathogenic factors, such as ischemia, nephrotoxic drugs, oxidative stress, inflammation, and urinary tract obstruction. Cell death, which is divided into several types, is critical for normal growth and development and maintaining dynamic balance. Ferroptosis, an iron-dependent nonapoptotic type of cell death, is characterized by iron overload, reactive oxygen species accumulation, and lipid peroxidation. Recently, growing evidence demonstrated the important role of ferroptosis in the development of various kidney diseases, including renal clear cell carcinoma, diabetic nephropathy, and AKI. However, the exact mechanism of ferroptosis participating in the initiation and progression of AKI has not been fully revealed. Herein, we aim to systematically discuss the definition of ferroptosis, the associated mechanisms and key regulators, and pharmacological progress and summarize the most recent discoveries about the role and mechanism of ferroptosis in AKI development. We further conclude its potential therapeutic strategies in AKI.

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“…ROS Detection in Kidneys. Dihydroethidium (DHE) was used to detect the ROS levels in the renal tissues, as previously reported [26]. The renal tissues were immersed in saccharose (30% w/v), embedded at the optimal cutting temperature (OCT), sliced into 5 μm sections, and stored at -20 °C until fluorescence detection.…”

Section: Determination Of Xo Activity and Expression In Serummentioning

confidence: 99%

Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Xanthine oxidase (XO) utilizes molecular oxygen as a substrate to convert purine substrates into uric acid, superoxide, and hydrogen peroxide, which is one of the main enzyme pathways to produce reactive oxygen species (ROS) during septic inflammation and oxidative stress. However, it is not clear whether XO inhibition can improve sepsis-induced renal hypoxia in sepsis-induced acute kidney injury (SI-AKI) mice. In this study, pretreatment with febuxostat, an XO-specific inhibitor, or kidney knockdown of XO by shRNA in vivo significantly improved the prognosis of SI-AKI, not only by reducing the levels of blood urea nitrogen, serum creatinine, tumor necrosis factor-α, interleukin-6, and interleukin-1β in peripheral blood but also by improving histological damage and apoptosis, reducing the production of ROS, and infiltrating neutrophils and macrophages in the kidney. More importantly, we found that pharmacological and genetic inhibition of XO significantly improved renal hypoxia in SI-AKI mice by a hypoxia probe via fluorescence staining. This effect was further confirmed by the decrease in hypoxia-inducible factor-1α expression in the kidneys of mice with pharmacological and genetic inhibition of XO. In vitro, the change in XO activity induced by lipopolysaccharide was related to the change in hypoxia in HK-2 cells. Febuxostat and XO siRNA significantly relieved the hypoxia of HK-2 cells cultured in 2% oxygen and reversed the decrease in cell viability induced by lipopolysaccharide. Our results provide novel insights into the nephroprotection of XO inhibition in SI-AKI, improving cell hypoxia by inhibiting XO activity and reducing apoptosis, inflammation, and oxidative stress.

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Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Cited by 37 publications

References 60 publications

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury via SIRT6-Mediated Autophagy Activation

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury via SIRT6-Mediated Autophagy Activation

Ferroptosis and Acute Kidney Injury (AKI): Molecular Mechanisms and Therapeutic Potentials

Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia

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