Prolyl hydroxylase inhibitor desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines and oxidative stress

Abstract Anisodamine hydrobromide (AniHBr) is a Chinese medicine used to treat septic shock. However, whether AniHBr could ameliorate septic acute kidney injury and the underlying mechanism were not investigated. In the present study, 18 male Sprague-Dawley rats (200–250 g) were randomly divided into control, lipopolysaccharide (LPS) and LPS+AniHBr groups. Rats were intravenously administrated with LPS or normal saline (for control). After 4 h, the rats were intravenously administrated with AniHBr (LPS+AniHBr) or normal saline at 4 h intervals. Hemodynamic parameters including blood pressure and heart rate were measured. The histopathologic evaluation of kidney tissues was performed. Lactate, creatine kinase, inflammatory cytokines and oxidative stress indicators were determined. Using Seahorse analysis, the metabolic analysis of mitochondrial stress and glycolytic stress in human renal proximal tubular epithelial cells treated with TNF-α in the presence of AniHBr was performed. AniHBr administration significantly reduced serum creatine kinase and lactate following LPS treatment. AniHBr significantly improved hemodynamics in sepsis rats including increase in the mean atrial pressure and reduction in the heart rate. AniHBr significantly attenuated LPS-induced TNF-α, IL-6 and IL-1β in serum, and LPS-induced TNF-α and IL-1β in renal tissues. The LPS-reduced SOD activity and LPS-increased MDA content were reversed by AniHBr. In vitro, TNF-α increased mitochondrial oxygen consumption and glycolysis, but inhibited the ATP generation, which was reversed by AniHBr. Thus, AniHBr protects against the LPS-induced inflammatory cytokines, mitochondrial dysfunction and oxidative stress, and thus attenuates the LPS-induced acute kidney injury, showing AniHBr is a promising therapeutic drug for septic kidney injury.

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Bisphenol A induces autophagy and oxidative stress in experimental chronic kidney injury and in tubular cells.

IBJ Plus ◽

10.24217/2531-0151.18v1s2.00115 ◽

2018 ◽

Author(s):

◽

Alberto Ruiz Priego ◽

Sandra Rayego Mateos ◽

Enrique Bosh Panadero ◽

...

Keyword(s):

Oxidative Stress ◽

Bisphenol A ◽

Kidney Injury ◽

Tubular Cells ◽

Chronic Kidney Injury ◽

And Oxidative Stress

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Targeting Inflammation and Oxidative Stress as a Therapy for Ischemic Kidney Injury

Biochemistry (Moscow) ◽

10.1134/s0006297920120111 ◽

2020 ◽

Vol 85 (12-13) ◽

pp. 1591-1602

Author(s):

N. V. Andrianova ◽

D. B. Zorov ◽

E. Y. Plotnikov

Keyword(s):

Oxidative Stress ◽

Kidney Injury ◽

And Oxidative Stress

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Fucoxanthin Ameliorates Oxidative Stress and Airway Inflammation in Tracheal Epithelial Cells and Asthmatic Mice

Cells ◽

10.3390/cells10061311 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1311

Author(s):

Shu-Ju Wu ◽

Chian-Jiun Liou ◽

Ya-Ling Chen ◽

Shu-Chen Cheng ◽

Wen-Chung Huang

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Airway Inflammation ◽

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Eosinophil Infiltration ◽

Tracheal Epithelial Cells ◽

Tracheal Epithelial ◽

And Oxidative Stress

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.

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Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Toxins ◽

10.3390/toxins13070472 ◽

2021 ◽

Vol 13 (7) ◽

pp. 472

Author(s):

Elisabetta Margiotta ◽

Lara Caldiroli ◽

Maria Luisa Callegari ◽

Francesco Miragoli ◽

Francesca Zanoni ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Interleukin 10 ◽

Uremic Toxins ◽

Interleukin 12 ◽

European Working ◽

And Oxidative Stress

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

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The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

Human & Experimental Toxicology ◽

10.1177/0960327115627688 ◽

2016 ◽

Vol 35 (12) ◽

pp. 1252-1263 ◽

Cited By ~ 23

Author(s):

SS Palabiyik ◽

E Karakus ◽

Z Halici ◽

E Cadirci ◽

Y Bayir ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Hepg2 Cells ◽

Folk Medicine ◽

Hepatoprotective Activity ◽

High Dose ◽

Protective Effects ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

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Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway

International Immunopharmacology ◽

10.1016/j.intimp.2021.108097 ◽

2021 ◽

Vol 100 ◽

pp. 108097

Author(s):

Jingnan Xu ◽

Shurou Li ◽

Liqiang Jiang ◽

Xinxin Gao ◽

Wei Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Kidney Injury ◽

Liver And Kidney

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Recurrent insulin-induced hypoglycemia induces AngII and COX2 leading to renal (pro)renin receptor expression and oxidative stress

International Journal of Medicine ◽

10.14419/ijm.v5i1.6858 ◽

2017 ◽

Vol 5 (1) ◽

pp. 71 ◽

Cited By ~ 1

Author(s):

Wael Alanazi ◽

Mohammad Uddin ◽

Selim Fakhruddin ◽

Keith Jackson

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Kidney Injury ◽

Organ Damage ◽

Day Surgery ◽

Receptor Expression ◽

Sprague Dawley ◽

Subunit Expression ◽

Renal Biomarker ◽

And Oxidative Stress

Background: Recurrent insulin-induced hypoglycemia (RIIH) is an avoidable consequence in the therapeutic management of diabetes mellitus. RIIH has been implicated in causing hypertension through an increase in renal and systemic AngII production.Objective: The present study was performed to assess the hypothesis that chronic insulin treatment enhances AngII and COX2 formation which in turn increases (pro) renin receptor (PRR) expression and NADPH oxidase-mediated oxidative stress, leading to renal and cardiac injury.Methods: The present studies were conducted in Male Sprague Dawley rats treated with daily subcutaneous injections of 7u/kg insulin or saline for 14 days. On the 14th day, surgery was performed for treatment infusion (captopril 12mg/kg, NS398 0.3mg/kg or vehicle), and renal interstitial fluid sample and urine collections for biomarker measurements. At the end of the experiments, kidneys and hearts were harvested to evaluate PRR and NOX2 (NADPH oxidase subunit) expression and oxidative stress.Results: We found that RIIH enhanced AngII and COX2 activity, leading to renal PRR expression and NADPH oxidase-induced oxidative stress in the heart and kidney. 8-isoprostane was evaluated as a renal biomarker of oxidative stress, which was induced in insulin treated animals and modulated by captopril and NS398. In addition, there was a slight increase in NGAL, a urinary biomarker of acute kidney injury (AKI), in insulin treated animals when compared to control.Conclusion: These results demonstrate that RIIH induces renal PRR expression and oxidative stress through increasing AngII and COX2 in the heart and kidney, leading to end-organ damage.

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