Involvement of Inflammasome Components in Kidney Disease

Aranda-Rivera, Ana Karina; Srivastava, Anjali; Cruz-Gregorio, Alfredo; Pedraza-Chaverri, José; Mulay, Shrikant R.; Scholze, Alexandra

doi:10.3390/antiox11020246

Cited by 30 publications

(12 citation statements)

References 348 publications

(432 reference statements)

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“…The spectrum of NF-κB targets is wide. It includes the inflammasome components NLRP3 and caspase-1, the inflammasome substrates pro-interleukin-1 and pro-interleukin-18 [ 129 ], adhesion molecules such as intercellular adhesion molecule 1 (ICAM), and tumor necrosis factor-alpha (TNF-α) [ 130 ]. The relation between Nrf2 and NF-κB is complex and bi-directional (for review see [ 96 , 98 ]).…”

Section: Clinical Data Of Nrf2 Activation In Human Ckdmentioning

confidence: 99%

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

et al. 2022

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The nuclear factor erythroid 2-related factor 2 (Nrf2) protects the cell against oxidative damage. The Nrf2 system comprises a complex network that functions to ensure adequate responses to redox perturbations, but also metabolic demands and cellular stresses. It must be kept within a physiologic activity range. Oxidative stress and alterations in Nrf2-system activity are central for chronic-kidney-disease (CKD) progression and CKD-related morbidity. Activation of the Nrf2 system in CKD is in multiple ways related to inflammation, kidney fibrosis, and mitochondrial and metabolic effects. In human CKD, both endogenous Nrf2 activation and repression exist. The state of the Nrf2 system varies with the cause of kidney disease, comorbidities, stage of CKD, and severity of uremic toxin accumulation and inflammation. An earlier CKD stage, rapid progression of kidney disease, and inflammatory processes are associated with more robust Nrf2-system activation. Advanced CKD is associated with stronger Nrf2-system repression. Nrf2 activation is related to oxidative stress and moderate uremic toxin and nuclear factor kappa B (NF-κB) elevations. Nrf2 repression relates to high uremic toxin and NF-κB concentrations, and may be related to Kelch-like ECH-associated protein 1 (Keap1)-independent Nrf2 degradation. Furthermore, we review the effects of pharmacological Nrf2 activation by bardoxolone methyl, curcumin, and resveratrol in human CKD and outline strategies for how to adapt future Nrf2-targeted therapies to the requirements of patients with CKD.

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Section: Clinical Data Of Nrf2 Activation In Human Ckdmentioning

confidence: 99%

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

et al. 2022

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“…Probiotic tests on other CKD models might be interesting because of the possible difference in interference of gut dysbiosis and inflammatory responses in individual CKD models. For example, gut dysbiosis might be more prominent in the oral adenine-induced CKD model due to its direct effect on intestinal microbiota with inflammasome-related inflammatory mechanisms (crystal-mediated inflammation) [ 75 , 76 , 77 , 78 ]. With gut dysbiosis attenuation and the anti-inflammatory properties of the probiotics, further exploration in other CKD models and clinical studies for a potential application in CKD are warranted.…”

Section: Discussionmentioning

confidence: 99%

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34

Tungsanga

Panpetch

Bhunyakarnjanarat

et al. 2022

IJMS

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A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-β-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 β; IL-1β) and inflammatory genes (TNF-α, IL-1β, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism.

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“…Caspase-1 activation promotes inflammatory cytokine interleukin-1 β (IL-1β) secretion; this process is predominantly regulated by NF-κB (Fujisawa et al, 2011;Mangali et al, 2019) and contributes to cisplatin-induced kidney injury (Aranda-Rivera et al, 2022).…”

Section: Cisplatin-induced Activation Of Caspase-1 and Interleukin-1β...mentioning

confidence: 99%

Genetic Knockout of Fatty Acid Amide Hydrolase Ameliorates Cisplatin-Induced Nephropathy in Mice

Chen¹,

Wang²,

Raymond³

et al. 2023

Mol Pharmacol

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Cisplatin is a potent first-line therapy for many solid malignancies such as breast, ovarian, lung, testicular and head and neck cancer. However, acute kidney injury (AKI) is a major dose-limiting toxicity in cisplatin therapy, which often hampers the continuation of cisplatin treatment. The endocannabinoid system, consisting of anandamide (AEA) and 2-arachidonoylglycerol and cannabinoid receptors, participates in different kidney diseases. Inhibition of fatty acid amide hydrolase (FAAH), the primary enzyme for the degradation of AEA and AEA-related N-acylethanolamines, elicits antiinflammatory effects; however, little is known about its role in cisplatin nephrotoxicity.The current study tested the hypothesis that genetic deletion of Faah mitigates cisplatininduced AKI. Male wild-type C57BL6 (WT) and Faah −/− mice were administered a single dose of intraperitoneal injection of cisplatin (30 mg/kg) and euthanatized 72 hours later.Faah −/− mice showed a reduction of cisplatin-induced blood urea nitrogen, plasma creatinine levels, kidney injury markers and tubular damage in comparison with WT mice. The renal protection from Faah deletion was associated with enhanced tone of AEA-related N-acylethanolamines (PEA and OEA), attenuated NF-κB/p65 activity, DNA damage markers p53, p21 and decreased expression of the inflammatory cytokine IL-1β as well as infiltration of macrophages and leukocytes in the kidneys. Notably, a selective FAAH inhibitor (PF-04457845) did not interfere with or perturb the antitumor effects of cisplatin in two head and neck squamous cell carcinoma cell lines, HN30 and HN12. Our work highlights that FAAH inactivation prevents cisplatin-induced nephrotoxicity in mice and that targeting FAAH could provide a novel strategy to mitigate cisplatin-induced nephrotoxicity.

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Involvement of Inflammasome Components in Kidney Disease

Cited by 30 publications

References 348 publications

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34

Genetic Knockout of Fatty Acid Amide Hydrolase Ameliorates Cisplatin-Induced Nephropathy in Mice

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