Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies DOI Creative Commons
Ademola C. Famurewa, Roland Eghoghosoa Akhigbe,

Mina Y. George

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Chemotherapy (CT) is one of the flagship options for treatment cancers worldwide. It involves use cytotoxic anticancer agents to kill or inhibit proliferation cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact patient’s quality life and outcomes. While toxicity consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment other aberrant signalling leading apoptosis necroptosis, recent studies show that ferroptosis, a non-apoptotic, iron-dependent cell death pathway, also involved pathophysiology organ toxicity. provokes ferroptosis via system Xc – /GPX-4/GSH/SLC7A11 axis depletion, ferritinophagy, iron overload, lipid peroxidation upregulation ferritin-related proteins. Cisplatin (CP) doxorubicin (DOX) are common drugs indicated induce vitro vivo. Studies have explored natural preventive therapeutic strategies using ginger rhizome major bioactive compounds, 6-gingerol (6G) zingerone (ZG), combat Ginger extract, 6G ZG mitigate dysfunction toxicity, but their effects on CT-induced remain unclear. Systematic investigations are, therefore, needed unfold roles ginger, as they potential prevention This review reveals ferroptotic protective against CT-induced, toxicities.

Language: Английский

Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases DOI Creative Commons
Jianying Yang,

Juyue Luo,

Xutong Tian

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 394 - 394

Published: March 25, 2024

Under normal physiological conditions, reactive oxygen species (ROS) are produced through redox reactions as byproducts of respiratory and metabolic activities. However, due to various endogenous exogenous factors, the body may produce excessive ROS, which leads oxidative stress (OS). Numerous studies have shown that OS causes a variety pathological changes in cells, including mitochondrial dysfunction, DNA damage, telomere shortening, lipid peroxidation, protein modification, all can trigger apoptosis senescence. also induces aging-related diseases, such retinal disease, neurodegenerative osteoarthritis, cardiovascular cancer, ovarian prostate disease. In this review, we aim introduce multiple internal external triggers mediate ROS levels rodents humans well relationship between OS, aging, diseases. Finally, present statistical analysis effective antioxidant measures currently being developed applied field aging research.

Language: Английский

Citations

77

The Potential of Superoxide Dismutase-Rich Tetraselmis chuii as a Promoter of Cellular Health DOI Open Access

Stuart P. Cocksedge,

Lalia Mantecón, Enrique Castaño

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1693 - 1693

Published: Feb. 16, 2025

Tetraselmis chuii (T. chuii) is a green, marine, eukaryotic, microalgae that was authorized in the European Union (EU) as novel food for human consumption 2014, and supplement 2017. This narrative review will provide an overview of preclinical clinical trials assessing efficacy T. chuii-derived ingredient, characterized by high superoxide dismutase (SOD) activity (SOD-rich chuii), to improve various aspects cellular health. Collectively, results from vitro, more importantly vivo research, support SOD-rich potential promoter Principally, ingredient appears function indirect antioxidant boosting intracellular systems. Moreover, it can positively modulate inflammatory status up-regulating anti-inflammatory down-regulating pro-inflammatory cytokines factors. In addition, promote health though protecting DNA damage, immune function, strengthening cell structure integrity, modulating signaling pathways. There also some evidence suggest may mitochondrial through up-regulation genes linked biogenesis ATP synthesis. From conducted date, transcriptional activation nuclear factor erythroid 2-related 2 (NRF2) sirtuin 1 (SIRT1) appear be important mediating effects on These exciting preliminary observations represent natural blue with enhance

Language: Английский

Citations

2

Cocoa flavanols, Nrf2 activation, and oxidative stress in peripheral artery disease: mechanistic findings in muscle based on outcomes from a randomized trial DOI
Ahmed Ismaeel, Mary Mcdermott, Jai K. Joshi

et al.

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(2), P. C589 - C605

Published: Jan. 8, 2024

The current study supports the hypothesis that in people with PAD, cocoa flavanols activate Nrf2, thereby increasing antioxidant protein levels, protecting against skeletal muscle damage, and mitochondrial abundance. These results suggest Nrf2 activation may be an important therapeutic target for improving walking performance PAD.

Language: Английский

Citations

13

Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway DOI Creative Commons

Sara A. Al-Kenany,

Nada N. Al-Shawi

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: June 12, 2023

Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) naturally occurring diterpene in unfiltered coffee unique antioxidant, antimutagenic, anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate potential chemoprotective of cafestol on DOX-induced cardiotoxicity rats. Wistar albino rats both sexes were administered (5 mg/kg/day) for 14 consecutive days oral gavage alone or doxorubicin which was injected as single dose (15 mg/kg intraperitoneally at day 14) induce toxicity. result showed that Caf significantly improved cardiac injury induced doxorubicin, decreased serum levels CK-MB, LDH, ALP, ALT, histopathological changes. In addition, inhibited stress seen reduced level MDA increased GSH, SOD, CAT, Gpx-1 tissue levels; enhanced gene protein expression promoted downstream antioxidant genes HO-1 NQO-1 downregulated Keap1 NF-κB genes' expression; inflammatory mediators, TNF-α, IL-1β modulating Bax Casp 3 TUNEL-positive cardiomyocytes. conclusion, confirmed effects regulation response pathway; this suggests may serve adjuvant chemotherapy alleviate toxicities.

Language: Английский

Citations

21

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches DOI Creative Commons
Sanaa Almowallad,

Rehab Al-Massabi

Saudi Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 31(5), P. 103977 - 103977

Published: March 11, 2024

Atherosclerosis is potentially correlated with several cardiac disorders that are greatly associated cellular oxidative stress generation, inflammation, endothelial cells dysfunction, and many cardiovascular complications. Berberine a natural isoquinoline alkaloid compound widely modulates pathogenesis of atherosclerosis through its different curative potentials. This in silico screening study was designed to confirm the potent restorative properties berberine chloride as multitarget-mediated against CVDs their complications screening, identifying, visualizing, evaluating binding models, affinities, interactions toward CVDs-related targets direct and/or indirect-mediated signals via inhibiting ER apoptotic activating autophagy pathway. The drug-likeness were predicted using computational QSAR/ADMET Lipinski's RO5 analyses well molecular docking simulations. berberine-binding modes, residues-interaction patterns, free energies scores towards estimated tools. Furthermore, pharmacokinetic toxicological features clearly determined. According this virtual study, could restore function improve pathogenic atherosclerotic alleviating signals, autophagy, improving insulin sensitivity, decreasing hyperglycemia dyslipidemia, increasing intracellular RCT signaling, attenuating vascular upregulating antioxidant defenses tissues. In modulated targets, including SIGMAR1, GRP78, CASP3, BECN1, PIK3C3, SQSTM1/p62, LC3B, GLUT3, INSR, LDLR, LXRα, PPARγ, IL1β, IFNγ, iNOS, COX-2, MCP-1, IL10, GPx1, SOD3.

Language: Английский

Citations

7

Targeting the redox system for cardiovascular regeneration in aging DOI Creative Commons
M Allemann,

Pratintip Lee,

Jürg H. Beer

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(12)

Published: Nov. 13, 2023

Abstract Cardiovascular aging presents a formidable challenge, as the process can lead to reduced cardiac function and heightened susceptibility cardiovascular diseases. Consequently, there is an escalating, unmet medical need for innovative effective regeneration strategies aimed at restoring rejuvenating tissues. Altered redox homeostasis accumulation of oxidative damage play pivotal role in detrimental changes stem cell cellular senescence, hampering regenerative capacity aged system. A mounting body evidence underscores significance targeting machinery restore self‐renewal enhance their differentiation potential into youthful lineages. Hence, holds promise target optimizing therapies. In this context, we delve current understanding regulating reprogramming processes that impact Furthermore, offer insights recent translational clinical implications redox‐targeting compounds enhancing therapies

Language: Английский

Citations

15

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule DOI Creative Commons
Xiaoyu Wu,

Jiajia Wei,

Wenfang Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 10, 2024

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis MI is exceedingly intricate, PANoptosis playing pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, phenylpropanoids, exhibits wide range pharmacological activities. However, it remains unclear whether XLGB can protect myocardium from damage after MI. This study aimed to investigate impact on isoprenaline (ISO)-induced mice potential mechanisms. Methods: assessed protective effects against ISO-induced through techniques such as echocardiography, HE staining, Masson enzyme-linked immunosorbent assay (ELISA). Furthermore, mechanisms XLGB's were explored using bioinformatics, molecular docking, dynamics simulations. These further validated immunofluorescence staining Western blotting. Results: results demonstrated that doses exhibited significant reduction myocardial injury induced by infarction. Intriguingly, higher dosages displayed superior therapeutic efficacy compared positive control metoprolol. effect primarily achieved inhibition oxidative stress inflammatory processes. we have elucidated protected MI-induced suppressing PANoptosis, critical played NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, compounds found directly interact NLRP3/Caspase3/RIP1, discovery docking suggests may be target for XLGB-induced protection. Conclusion: In summary, our findings reveal novel property XLGB: reverses following inhibiting NLRP3/Caspase3/RIP1-mediated

Language: Английский

Citations

6

The antiosteoporotic effect of oxymatrine compared to testosterone in orchiectomized rats DOI Creative Commons

Anwaar M. Shaban,

Eman A. Ali,

Sara G. Tayel

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 9, 2025

Castration of adult male rats led to the development osteoporosis. Oxidative stress and inflammatory factors have been identified as potential causative factors. Notably, oxymatrine (OMT) possesses potent anti-inflammatory antioxidant activities. This study aims elucidate antiosteoporotic effects OMT compared testosterone in an orchiectomized (ORX) rat model A total 60 Wistar were divided into following groups: control (CTRL), surgery + no orchiectomy (SHAM), ORX, ORX testosterone, OMT. Urinary deoxypyridinoline (DPD), calcium (Ca), phosphorus (P), well serum parathormone (PTH), alkaline phosphatase (ALP), osteocalcin, N-telopeptide type I collagen (NTX I), tartrate resistance acid (TRAP), Ca P levels evaluated. Bone was assessed for malondialdehyde (MDA), reduced glutathione (GSH), interleukin 6 (IL-6), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related 2 (Nrf2), heme oxygenase (HO-1) expression, receptor activator κB ligand/ osteoprotegerin (RANKL/OPG) ratio. dual-energy X-ray absorptiometry (DEXA) scan histological immunohistochemical studies performed. Testosterone or treatment ameliorated bone mineral density (BMD) content (BMC) DEXA changes PTH levels. Compared group, formation, turnover markers also significantly reversed groups. Treatment with MDA, IL-6, Keap1, RANKL, RANKL/OPG ratio, elevated GSH, Nrf2, HO-1. Moreover, has restored cortical thickness osteocyte number TNF-α rats. Consequently, either exhibited nearly equal therapeutic efficacy; however, neither them could normalize measured parameters. showed efficacy ameliorating osteoporosis rats, possibly by improving some oxidative

Language: Английский

Citations

0

Dietary Supplements as Modulators of the Nrf2 Pathway to Enhance Intracellular Antioxidant Responses and Protect Against Dyslipidemia-Associated Cardiovascular Complications DOI
Sinenhlanhla X. H. Mthembu, Sithandiwe E. Mazibuko-Mbeje, Sonia Silvestri

et al.

Food Reviews International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 29

Published: Jan. 23, 2025

The market for dietary supplements has significantly grown due to their envisaged health benefits. These bioactive compounds are actively explored therapeutic benefits against vast metabolic complications abundant antioxidant properties. Nuclear factor erythroid 2-related 2 (Nrf2) modulation as a cytoprotective mechanism oxidative stress-induced stress garnered interest, particularly through its regulation by many supplements. This review aims evaluate and critically discuss the available evidence on potential effects of supplements, including prominently used nutraceuticals dyslipidemia-associated cardiovascular complications. Notably, this highlights these modulate Nrf2 pathway, enhancing intracellular antioxidants providing protection Beyond value preclinical ability regulate pathway counteract damage, also incorporates clinical supporting in dyslipidemia-related conditions. Fundamental pharmacological aspects such bioavailability relevant biological properties discussed inform further development diseases.

Language: Английский

Citations

0

Ameliorative Effect of N-Acetylcysteine Against 5-Fluorouracil-Induced Cardiotoxicity via Targeting TLR4/NF-κB and Nrf2/HO-1 Pathways DOI Creative Commons
Omer Abdelbagi, Medhat Taha,

Abdullah G. Al-Kushi

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 335 - 335

Published: Feb. 14, 2025

Background and Objectives: 5-Fluorouracil (5-FU) is a widely prescribed effective chemotherapeutic drug, but its cardiotoxic side effects pose significant challenge to use. Identifying protective agent that does not affect anticancer efficacy essential. Our study aimed investigate the cardioprotective effect of N-acetyl cysteine (NAC) against 5-FU-induced cardiac injury elucidate underlying mechanisms. Materials Methods: This included four experimental groups, each with eight rats (n = 8): Group I (control group), II (NAC III (5-FU IV (combined group 5-FU+NAC). Cardiac enzymes, oxidative stress, inflammatory, apoptotic markers were investigated, sections from different groups histologically examined. Results: Co-treatment 5-FU NAC resulted in significantly lower levels enzymes (alanine transaminase (ALT) by 62.1%, aspartate (AST) 73.6%, lactate dehydrogenase (LDH) 55.8%, creatine kinase (CK) 57.3%) compared group, along marked improvements heart tissue histology. Additionally, enhanced activity antioxidant (superoxide dismutase (SOD) 295.6%, catalase (CAT) 181%, glutathione peroxidase (GPx) 320.9%) while decreasing malondialdehyde (MDA) 51.1%, marker membranous lipid peroxidation. might be due upregulation nuclear factor erythroid-2-related 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway at gene protein levels. The combined treatment decreased expression toll-like receptor 4 (TLR4)/nuclear kappa-light-chain-enhancer activated B-cell (NF-κB) pathway. Furthermore, it downregulated inflammatory markers, including tumor necrosis factor-alpha (TNF-α) 29.9%, interleukin-1 beta (IL-1β) 21.9%, interleukin-6 (IL-6) 49.3%. Moreover, upregulated antiapoptotic lymphoma (Bcl-2) 269% indicators Bcl-2-associated x (Bax) 57.9% caspase-3 30.6% group. Conclusions: confirmed prevented through antioxidant, anti-inflammatory, properties, suggesting potential application as an adjuvant therapy chemotherapy alleviate cardiotoxicity.

Language: Английский

Citations

0