SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

Xu, Siqi; Gao, Youguang; Zhang, Qin; Wei, Siwei; Chen, Zhongqing; Dai, Xingui; Zeng, Zhenhua; Zhao, Ke‐seng

doi:10.1155/2016/7296092

Cited by 135 publications

(123 citation statements)

References 29 publications

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“…Increasing evidence has suggested that SIRT1 is implicated in renal physiology and pathology, and plays a renal protective role against inflammatory injury [ 31 ]. For example, Xu et al reported that SIRT1/3 activation by resveratrol attenuated AKI following sepsis in a septic rat model [ 32 ]. Wang et al uncovered that resveratrol, a SIRT1 activator, ameliorated the renal tubular injury induced by hyperglycemia both in vitro and in vivo via suppressing apoptosis [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Ginkgetin aglycone ameliorates LPS-induced acute kidney injury by activating SIRT1 via inhibiting the NF-κB signaling pathway

et al. 2017

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BackgroundGinkgetin aglycone (GA), a novel Ginkgo biloba extract (GBE) by acid hydrolysis and recrystallization, is characterized by higher liposolubility and antioxidation than classical GBEs. There is no study depicting the functional role of GA in acute kidney injury (AKI). Here, we firstly reported the protective effect of GA on lipopolysaccharide (LPS)-induced AKI and its underlying mechanism.MethodsELISA analysis was applied to measure plasma level of TNF-α and IL-6, and NF-κB activity in kidney homogenate. Renal function analysis was performed by detecting serum concentration of Kim-1 and urine level of BUN. Cell apoptosis in kidney tissues was detected by TUNEL assay and caspase-3 activity assay. qRT-PCR was conducted to determine mRNA expression of TNF-α, IL-6 and IκBα. Western blot was carried out to confirm expression of p-IκBα, SIRT1, and iNOS.ResultsGA administration protected mice from LPS-induced AKI by attenuating inflammatory response, renal injury, as well as tubular apoptosis both in vivo. GA suppressed inflammatory response induced by LPS in HK-2 cells. Moreover, GA upregulated SIRT1 expression and blocked the NF-κB signaling pathway in LPS-induced AKT in vivo and vitro. Furthermore, suppression of SIRT1 abated the inhibitory effect of GA on LPS-induced inflammatory response and renal injury.ConclusionsGA prevented LPS-induced AKI by activating SIRT1 via inhibiting the NF-κB signaling pathway, providing new insights into the function and molecular mechanism of GA in AKI. Therefore, GA may be a promising therapeutic agent for the treatment of septic AKI.

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Section: Discussionmentioning

confidence: 99%

Ginkgetin aglycone ameliorates LPS-induced acute kidney injury by activating SIRT1 via inhibiting the NF-κB signaling pathway

et al. 2017

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“…MD plays an important role in several diseases, including AKI [19,29,30]. Additionally, MD is often associated with the triggering of mitophagy pathways, which eliminate dysfunctional or impaired mitochondria [6,31].…”

Section: Discussionmentioning

confidence: 99%

“…Sepsis was induced by caecal ligation and puncture (CLP). As previously described [19], a midline incision was made with minimal dissection, and caecal ligation was performed just below the ileocaecal valve to maintain intestinal continuity. Then, a 7-gauge needle was used to make a single perforation in the caecum, which was gently pressed until all the faeces were drained.…”

Section: Establishment Of a Sepsis Model By Caecal Ligation And Puncturementioning

confidence: 99%

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Gao

Dai

et al. 2020

J Transl Med

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Background: We have reported that polydatin (PD) alleviates mitochondrial dysfunction in rat models of sepsisinduced acute kidney injury (SI-AKI), but the mechanism is not well understood. Here, we investigated the role of Parkin-mediated mitophagy in the protective effects of PD in SI-AKI in mice. Methods: Sepsis was induced in the mice by caecal ligation and puncture. Mitophagy was determined by mitochondrial mass. NLRP3 inflammasome activation was determined by NLRP3, ASC and caspase-1. Mitophagy was blocked by treatment with mitochondrial division inhibitor-1 and Parkin knockout. Key results: PD treatment increased the sepsis-induced loss of mitochondrial mass, indicating the upregulation of mitophagy. Furthermore, PD treatment mediated Parkin translocation from the cytoplasm to the mitochondria. This suggests that Parkin-mediated mitophagy is an underlying mechanism. This was confirmed by the suppression of PD-induced mitophagy in Parkin−/− mice and in mice that were treated with a mitophagy inhibitor. PD-induced Parkin translocation and mitophagy were blocked by inhibiting SIRT1; thus, activation of SIRT1 might be an important molecular mechanism that is triggered by PD. Additionally, PD treatment protected against sepsis-induced kidney injury. These effects were blocked by inhibition of Parkin-dependent mitophagy. Furthermore, PD also protected against mitochondrial dysfunction and mitochondria-dependent apoptosis, and the effect was blocked when Parkindependent mitophagy was inhibited. Finally, PD suppressed NLRP3 inflammasome activation that was also dependent on Parkin-mediated mitophagy. Conclusions: These findings indicate that Parkin-mediated mitophagy is important for the protective effect of PD in SI-AKI, and the underlying mechanisms include the inhibition of mitochondrial dysfunction and NLRP3 inflammasome activation.

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“…mitochondria apoptosis in cardiomyocytes 35 and acute kidney injury in a septic rat model, 36 which is also reversed by EX527. The reason for RES and EX527 modulating protein expression of SIRT1 may be that RES (►Fig.…”

Section: Discussionmentioning

confidence: 98%

Deep Vein Thrombosis is Modulated by Inflammation Regulated via Sirtuin 1/NF-κB Signalling Pathway in a Rat Model

et al. 2019

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Background Inflammation plays an important role in thrombus formation, and Sirtuin 1 (SIRT1) negatively regulates inflammation via deacetylating nuclear factor-kappa B. However, the relationship between SIRT1-regulated inflammation and deep vein thrombosis (DVT) is still unknown. Objective The aim of this study was to investigate whether SIRT1 plays a critical role in inferior vena cava (IVC) stenosis-induced DVT. Materials and Methods Thrombus weight and histopathologic analysis of IVC were evaluated at different time points after IVC stenosis in rats. Serum levels of inflammatory cytokines and protein expressions of SIRT1, acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF) in thrombosed IVC were assessed. Besides, the effects of resveratrol (RES, a SIRT1 agonist) and EX527 (a selective SIRT1 inhibitor) on DVT were evaluated. Results Thrombus weight was increased from 1 to 3 days after IVC stenosis, and then was decreased afterwards. Leukocytes infiltration appeared and serum levels of cytokines were significantly increased in rats of IVC stenosis. SIRT1 protein expression was significantly down-regulated at 1 hour and 1 day after stenosis, while p-p65, Ace-p65 and TF protein expressions appeared a contrary trend. RES reduced thrombus weight, leukocytes infiltration, levels of tumour necrosis factor-α and interleukin-1β and protein expressions of Ace-p65 and TF as well. Moreover, RES significantly increased the protein and messenger ribonucleic acid expressions of SIRT1, while EX527 abolished the protective effects of RES. Conclusion SIRT1 activation attenuated IVC stenosis-induced DVT via anti-inflammation in rats. Therefore, SIRT1 may be a potential therapeutic target that could ameliorate DVT.

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SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

Cited by 135 publications

References 29 publications

Ginkgetin aglycone ameliorates LPS-induced acute kidney injury by activating SIRT1 via inhibiting the NF-κB signaling pathway

Ginkgetin aglycone ameliorates LPS-induced acute kidney injury by activating SIRT1 via inhibiting the NF-κB signaling pathway

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Deep Vein Thrombosis is Modulated by Inflammation Regulated via Sirtuin 1/NF-κB Signalling Pathway in a Rat Model

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