Advanced oxidation protein products upregulate efflux transporter expression and activity through activation of the Nrf-2-mediated signaling pathway in vitro and in vivo

Xun, Tianrong; Lin, Zhufen; Zhan, Xia; Song, Shushu; Mo, Liqian; Feng, Haixing; Yang, Qin; Guo, Dan; Yang, Xiaoxia

doi:10.1016/j.ejps.2020.105342

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…On the other hand, the protein level of Nrf2 was decreased by fisetin. Nrf2 is involved in the counteraction of oxidative modifications during hypoxia and enhances the expression of a number of stress-responsive genes that control survival, metabolic reprogramming, proliferation, and drug resistance [ 34 , 35 ]. ABCB1, ABCC1, and ABCG2 are highly expressed in the cisplatin-resistant A549 cells compared to parent cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Increase in Anticancer Drug-Induced Toxicity by Fisetin in Lung Adenocarcinoma A549 Spheroid Cells Mediated by the Reduction of Claudin-2 Expression

Eguchi

Kimura

Matsunaga

et al. 2022

IJMS

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Claudin-2 (CLDN2), a component of tight junction, is involved in the reduction of anticancer drug-induced toxicity in spheroids of A549 cells derived from human lung adenocarcinoma. Fisetin, a dietary flavonoid, inhibits cancer cell growth, but its effect on chemosensitivity in spheroids is unknown. Here, we found that fisetin (20 μM) decreases the protein level of CLDN2 to 22.3%. Therefore, the expression mechanisms were investigated by real-time polymerase chain reaction and Western blotting. Spheroids were formed in round-bottom plates, and anticancer drug-induced toxicity was measured by ATP content. Fisetin decreased the phosphorylated-Akt level, and CLDN2 expression was decreased by a phosphatidylinositol 3-kinase (PI3K) inhibitor, suggesting the inhibition of PI3K/Akt signal is involved in the reduction of CLDN2 expression. Hypoxia level, one of the hallmarks of tumor microenvironment, was reduced by fisetin. Although fisetin did not change hypoxia inducible factor-1α level, it decreased the protein level of nuclear factor erythroid 2-related factor 2, a stress response factor, by 25.4% in the spheroids. The toxicity of doxorubicin (20 μM) was enhanced by fisetin from 62.8% to 40.9%, which was rescued by CLDN2 overexpression (51.7%). These results suggest that fisetin can enhance anticancer drug toxicity in A549 spheroids mediated by the reduction of CLDN2 expression.

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Section: Discussionmentioning

confidence: 99%

“…ABCB1, ABCC1, and ABCG2 are highly expressed in the cisplatin-resistant A549 cells compared to parent cells [ 36 ]. Nrf2 promotes transcriptional activation of ABC transporters [ 34 ]. In addition, ABCC1 expression is decreased by transfection of Nrf2 shRNA in the cisplatin-resistant A549 cells [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Increase in Anticancer Drug-Induced Toxicity by Fisetin in Lung Adenocarcinoma A549 Spheroid Cells Mediated by the Reduction of Claudin-2 Expression

Eguchi

Kimura

Matsunaga

et al. 2022

IJMS

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“…The concentration of advanced oxidative protein products (AOPPs) in serum was detected as described in our published article. 16 Briefly, 200 μL aliquots of chloramine-T (0, 20, 40, 80, and 100 μM), 200 μL of serum samples, and 200 μL PBS were added to a 96-well plate. Potassium iodide (10 μL, 1.16 mol/L) and acetic acid (20 μL) were then added to each well.…”

Section: Methodsmentioning

confidence: 99%

Huang Gan Formula Alleviates Systemic Inflammation and Uremia in Adenine-Induced Chronic Kidney Disease Rats May Associate with Modification of Gut Microbiota and Colonic Microenvironment

Zhao,

Xun

et al. 2024

DDDT

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Purpose This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD. Methods CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson’s trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman’s rank correlation coefficient were used for correlation analysis. Results HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1β, TGF-β1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10. Conclusion Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.

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“…At 24 h post-transfection, cells were treated with or without p65 (200 or 400 ng), and firefly and Renilla luciferase reporter signals were immediately determined using the Dual-Luciferase Reporter Gene Assay System (Promega). 19 …”

Section: Methodsmentioning

confidence: 99%

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

Wang,

Hu,

et al. 2024

J Clin Transl Hepatol

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Background and Aims Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism. Methods First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharide-induced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance assessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis. Results The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum , which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway. Conclusions The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

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Advanced oxidation protein products upregulate efflux transporter expression and activity through activation of the Nrf-2-mediated signaling pathway in vitro and in vivo

Cited by 8 publications

References 47 publications

Increase in Anticancer Drug-Induced Toxicity by Fisetin in Lung Adenocarcinoma A549 Spheroid Cells Mediated by the Reduction of Claudin-2 Expression

Increase in Anticancer Drug-Induced Toxicity by Fisetin in Lung Adenocarcinoma A549 Spheroid Cells Mediated by the Reduction of Claudin-2 Expression

Huang Gan Formula Alleviates Systemic Inflammation and Uremia in Adenine-Induced Chronic Kidney Disease Rats May Associate with Modification of Gut Microbiota and Colonic Microenvironment

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

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