Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities

Lokman, Maha S.; Althagafi, Hussam A.; Alharthi, Fahad; Habotta, Ola A.; Hassan, Amr; Elhefny, Mohamed A; Sberi, Hassan Al; Theyab, Abdulrahman; Mufti, Ahmad H.; Alhazmi, Alaa; Hawsawi, Yousef M.; Khafaga, Asmaa F.; Gewaily, Mahmoud S.; Alsharif, Khalaf F.; Albrakati, Ashraf; Kassab, Rami B.

doi:10.1007/s11356-022-23314-z

Cited by 12 publications

(3 citation statements)

References 61 publications

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“… 52–54 Upon being activated, NF-κB moves to the nucleus and phosphorylates its p65 subunit, this triggers elevation of pro-inflammatory cytokines eg, IL-1β. 55 , 56 Wang et al 57 reported that MM and cyanuric acid co-treatment increased the phosphorylation level of NF-κB as well as the mRNA expression of NLRP3 inflammasome in the kidney in rats. Increased NF-κB expression levels in hepatocytes of MM-exposed rats was observed which indicated that inflammatory reaction mediated by MM exposure.…”

Section: Discussionmentioning

confidence: 99%

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events

Abdelrahaman,

Habotta,

Ateya

et al. 2024

DDDT

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Background Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage. Methods Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg). Results The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK’s ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1β and TNF-α, besides downregulation of NF-κB and IL-1β expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features. Conclusion These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.

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Section: Discussionmentioning

confidence: 99%

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events

Abdelrahaman,

Habotta,

Ateya

et al. 2024

DDDT

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“…Under an undesirable condition of oxidative stress, Keap1 triggers the activation of Nrf2 and its downstream-regulated genes [ 56 ]. Nrf2 regulates the induction of detoxification enzymes and antioxidants such as HO-1 for scavenging of deleterious radicals and maintenance of cellular homeostasis [ 57 , 58 ]. Recent articles, in accordance with our study, have reported that CDDP results in down-regulation of Nrf2 and its related antioxidant enzymes [ 7 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, CDDP injection significantly increased the levels of TNF-α and IL-6 as well as the mRNA expression of NF-κB in the mouse kidneys. NF-κB is the hub of many signaling pathways and its activation enhances the transcription of various pro-inflammatory cytokines [ 57 , 71 ]. It was documented that the activation of NF-κB is the main dedicator of renal inflammation under CDDP challenge [ 5 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic activity of green synthesized selenium nanoparticles from turmeric against cisplatin-induced oxido-inflammatory stress and cell death in mice kidney

ALRashdi,

Mohamed,

Mohamed

et al. 2023

Bioscience Reports

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Cisplatin (CDDP) is a commonly prescribed chemotherapeutic agent; however, its associated nephrotoxicity limits its clinical efficacy and sometimes requires discontinuation of its use. The existing study was designed to explore the reno-therapeutic efficacy of turmeric (Tur) alone or conjugated with selenium nanoparticles (Tur-SeNPs) against CDDP-mediated renal impairment in mice and the mechanisms underlying this effect. Mice were orally treated with Tur extract (200 mg/kg) or Tur-SeNPs (0.5 mg/kg) for 7 days after administration of a single dose of CDDP (5 mg/kg, i.p.). N-acetyl cysteine NAC (100 mg/kg) was used as a standard antioxidant compound. The results revealed that Tur-SeNPs counteracted CDDP-mediated serious renal effects in treated mice. Compared with the controls, Tur or Tur-SeNPs therapy remarkably decreased the kidney index along with the serum levels of urea, creatinine, Kim-1, and NGAL of the CDDP-injected mice. Furthermore, Tur-SeNPs ameliorated the renal oxidant status of CDDP group demonstrated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and gene expression levels of HO-1. Noteworthy, lessening of renal inflammation was exerted by Tur-SeNPs via lessening of IL-6 and TNF-α besides down-regulation of NF-κB gene expression in mouse kidneys. Tur-SeNPs treatment also restored the renal histological features attained by CDDP challenge and hindered renal apoptosis through decreasing the Bax levels and increasing Bcl-2 levels. Altogether, these outcomes suggest that the administration of Tur conjugated with SeNPs is effective neoadjuvant chemotherapy to guard against the renal adverse effects that are associated with CDDP therapy.

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Sodium‐Glucose Co‐Transporter‐2 Inhibitor Empagliflozin Attenuates Sorafenib‐Induced Myocardial Inflammation and Toxicity

Liu,

Ho,

Lee

et al. 2024

Environmental Toxicology

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Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real‐time quantitative RT‐PCR (qRT‐PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib‐treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28‐day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib‐induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT‐dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib‐treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib‐promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib‐stimulated proinflammatory signaling (TNF‐α/IL‐1β/IL‐6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib‐promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

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Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities

Cited by 12 publications

References 61 publications

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events

Therapeutic activity of green synthesized selenium nanoparticles from turmeric against cisplatin-induced oxido-inflammatory stress and cell death in mice kidney

Sodium‐Glucose Co‐Transporter‐2 Inhibitor Empagliflozin Attenuates Sorafenib‐Induced Myocardial Inflammation and Toxicity

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