Nephroprotective Effects of N‐Acetylcysteine Amide against Contrast‐Induced Nephropathy through Upregulating Thioredoxin‐1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats

Gong, Xuezhong; Duan, Yue; Zheng, Junli; Wang, Yiquan; Wang, Guohua; Norgren, Svante; Hei, Tom K.

doi:10.1155/2016/8715185

Cited by 39 publications

(28 citation statements)

References 40 publications

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“…Antioxidant N-acetylcysteine (NAC) is getting more attention because of its ability to alleviate CI-AKI. N-acetylcysteine amide (NACA) is an amide of NAC, and it can mitigate oxidative stress and reduce apoptosis more effective than NAC through p38 MAPK [77]. In ischemia tissue, phosphatidylinositol-3 kinase/serine-threonine kinase B (P13K/Akt) and its downstream molecules play a role in cell protection and survival [78].…”

Section: E Possible Targeting Pathways In Relieving Ci-akimentioning

confidence: 99%

The Mechanism of Contrast-Induced Acute Kidney Injury and Its Association with Diabetes Mellitus

Kawaguchi

2020

Contrast Media & Molecular Imaging

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Contrast-induced acute kidney injury (CI-AKI) is the third most common hospital-acquired AKI after AKI induced by renal perfusion insufficiency and nephrotoxic drugs, taking great adverse effects on the prognosis and increasing hospital stay and medical cost. Diabetes nephropathy (DN) is a common chronic complication of DM (diabetes mellitus), and DN is an independent risk factor for chronic kidney disease (CKD) and CI-AKI. The incidence of CI-AKI significantly increases in patients with renal injury, especially in DM-related nephropathy. The etiology of CI-AKI is not fully clear, and research studies on how DM becomes a facilitated factor of CI-AKI are limited. This review describes the mechanism from three aspects. ① Pathophysiological changes of CI-AKI in kidney under high-glucose status (HGS). HGS can enhance the oxidative stress and increase ROS which next causes stronger vessel constriction and insufficient oxygen supply in kidney via vasoactive substances. HGS also aggravates some ion pump load and the latter increases oxygen consumption. CI-AKI and HGS are mutually causal, making the kidney function continue to decline. ② Immunological changes of DM promoting CI-AKI. Some innate immune cells and pattern recognition receptors (PRRs) in DM and/or DN may respond to some damage-associated molecular patterns (DAMPs) formed by CI-AKI. These effects overlap with some pathophysiological changes in hyperglycemia. ③ Signaling pathways related to both CI-AKI and DM. These pathways involved in CI-AKI are closely associated with apoptosis, inflammation, and ROS production, and some studies suggest that these pathways may be potential targets for alleviating CI-AKI. In conclusion, the pathogenesis of CI-AKI and the mechanism of DM as a predisposing factor for CI-AKI, especially signaling pathways, need further investigation to provide new clinical approaches to prevent and treat CI-AKI.

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Section: E Possible Targeting Pathways In Relieving Ci-akimentioning

confidence: 99%

The Mechanism of Contrast-Induced Acute Kidney Injury and Its Association with Diabetes Mellitus

Kawaguchi

2020

Contrast Media & Molecular Imaging

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“…p38MAPK pathway has been shown to be involved in apoptosis [44]. In previous study, 6-OHDA induces apoptosis through p38MAPK-dependent, TP53-independent activation of Bax in the rat model of PD [45].…”

Section: Discussionmentioning

confidence: 87%

NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation

Zhou

Zhu

et al. 2018

Acta Pharmacol Sin

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Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP. In the present study, NADPH prevented DA neurons from MPTP toxicity with increased GSH and decreased reactive oxygen species (ROS) levels in the ventral midbrain of mice, and improved motor activity. Our present results demonstrated that NADPH inhibited the phosphorylation of p38MAPK, decreased the level of TP53 protein, and inhibited TP53 nuclear translocation in DA neurons of SNpc and in MES23.5 cells. Furthermore, NADPH decreased the protein level of TP53 target gene, Bax, cleavage of PARP, and nuclei condensation. Taken together, NADPH abrogated MPTP-induced p38MAPK phosphorylation, TP53 nuclear translocation, and Bax induction, and finally, MPTP/MPP-induced apoptosis of DA neurons. This study suggests that NADPH may be a novel therapeutic candidate for PD.

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“…Many reports illustrate that ASK1 can contribute to the development and progression of inflammatory response [30,31]. For example, the bacterial infection-engaged inhibition of ASK1 is responsible for regulating Erk1/2- and p38-MAPKs activation, but not JNK-MAPK signaling [31,32]. This previous studies suggest that ASK1 and p38 have close relationship in inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

ASK1/p38-mediated NLRP3 inflammasome signaling pathway contributed to aberrant retinal angiogenesis in diabetic retinopathy

Zhou¹,

Zhang²,

Luo³

et al. 2019

Preprint

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Abstracts: Diabetic retinopathy is the leading cause of blindness in the working-age 18 population in many countries. Despite the available treatments, some patients present 19 late in the course of the disease when treatment is more difficult. Hence, it is crucial 20 that the new targets are found and utilized in clinical therapy of diabetic retinopathy. 21In this study, we constructed the DR animal model and the high model in HRMEC 22 cell to investigate the relationship between ASK1/p38 and NLRP3 in DR. The results 23 showed that DR could cause the inflammatory response and microvascular 24 proliferation. NLRP3 contributed to DR-mediated inflammatory development and 25 progression, which promoted the inflammatory related cytokine expression. 26 Meanwhile, it could promote the tube formation of retinal microvascular endothelial 27 and angiogenesis. Moreover, further research showed that NLRP3 mediated aberrant 28 retinal angiogenesis in diabetic retinopathy was regulated by ASK1 and p38. It 29 suggested that ASK1/p38 could become a new target in DR treatment.30

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Nephroprotective Effects of N‐Acetylcysteine Amide against Contrast‐Induced Nephropathy through Upregulating Thioredoxin‐1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats

Cited by 39 publications

References 40 publications

The Mechanism of Contrast-Induced Acute Kidney Injury and Its Association with Diabetes Mellitus

The Mechanism of Contrast-Induced Acute Kidney Injury and Its Association with Diabetes Mellitus

NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation

ASK1/p38-mediated NLRP3 inflammasome signaling pathway contributed to aberrant retinal angiogenesis in diabetic retinopathy

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