A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis

Redox Biology, Год журнала: 2022, Номер 57, С. 102511 - 102511

Опубликована: Окт. 14, 2022

Natural antioxidants represented by quercetin have been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. In this study, we identified a novel anti-atherosclerotic mechanism of inhibiting macrophage pyroptosis activating NRF2 through binding Arg483 site KEAP1 competitively. ApoE-/- mice fed with high fat diet, administration attenuated atherosclerosis progression reducing oxidative stress level and suppressing pyroptosis. At cellular level, suppressed THP-1 induced ox-LDL, demonstrated NLRP3 inflammasome activation ROS while these effects were reversed specific inhibitor (ML385). Mechanistically, promoted dissociate from KEAP1, enhanced nuclear translocation as well transcription downstream antioxidant protein. Molecular docking results suggested that could bind at Arg415 Arg483. order verify sites, mutated Ser (R415S R483S) was transfected into macrophages, anti-pyroptotic effect abrogated mutation, but not mutation. Furthermore, after adeno associated viral vector (AAV) AAV-KEAP1-R483S, almost abolished in mice. These findings proved quercetins targeting KEAP1/NRF2 interaction, provided reliable data on underlying natural protect

Язык: Английский

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Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways

Antioxidants, Год журнала: 2024, Номер 13(2), С. 180 - 180

Опубликована: Янв. 31, 2024

Benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon primarily formed during incomplete organic matter combustion, undergoes series of hepatic metabolic reactions once absorbed into the body. B[a]P contributes to liver damage, ranging from molecular DNA damage onset and progression various diseases, including cancer. Specifically, induces oxidative stress via reactive oxygen species generation within cells. Consequently, more research has focused on exploring underlying mechanisms B[a]P-induced potential strategies counter its toxicity. Flavonoids, natural compounds abundant in plants renowned for their antioxidant properties, possess ability neutralize adverse effects free radicals effectively. Although extensive investigated flavonoids, limited delved regulating metabolism alleviate stress. This review aims consolidate current knowledge examines role flavonoids mitigating

Язык: Английский

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Urtica pilulifera leaves extract mitigates cadmium induced hepatotoxicity via modulation of antioxidants, inflammatory markers and Nrf-2 signaling in mice

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Фев. 26, 2024

Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl 2 ) mice. Methods: In vitro phytochemical screening and metal-chelating activity UPLE were ascertained. Four groups forty male mice used ( n = 10) as follows; Group 1 (G1) was negative control. G2 injected i.p., with (100 mg/kg b. wt) daily. G3 Cd (5 G4 G2. On day 11, body weight changes evaluated, blood, serum samples collected for hematological biochemical assessments. Liver tissues biochemical, molecular, histopathological investigations. Results: The contains promising secondary metabolites considerably lessen effects on liver. Furthermore, inhibited oxidative stress inflammation; restored antioxidant molecules; promoted nuclear-related factor-2 (Nrf-2) expression. Also, improved alterations Cd. Discussion: explored beneficial role treatment Cd-induced liver injury through enhancing Nrf-2 signaling enzyme gene expression Therefore, could have valuable implications environmental exposure. Which can be chelating agent

Язык: Английский

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Liver Injury Induced by Exposure to Polystyrene Microplastics Alone or in Combination with Cadmium in Mice Is Mediated by Oxidative Stress and Apoptosis

Biological Trace Element Research, Год журнала: 2023, Номер 202(5), С. 2170 - 2183

Опубликована: Сен. 22, 2023

Язык: Английский

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Molecular mechanism of caloric restriction mimetics-mediated neuroprotection of age-related neurodegenerative diseases: an emerging therapeutic approach

Biogerontology, Год журнала: 2023, Номер 24(5), С. 679 - 708

Опубликована: Июль 10, 2023

Язык: Английский

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Therapeutic Potential of Clove Oil in Mitigating Cadmium-Induced Hepatorenal Toxicity Through Antioxidant, Anti-Inflammatory, and Antiapoptotic Mechanisms

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 94 - 94

Опубликована: Янв. 14, 2025

Hazardous heavy metals, particularly cadmium (Cd), are widely distributed in the environment and cause oxidative stress various animal human organs. Clove oil (CLO), a common aromatic spice, has been used as traditional medication it potent anti-inflammatory, antioxidant, hepatoprotective properties. This study aimed to investigate antiapoptotic, anti-inflammatory effects of clove (CLO) against hepatorenal toxicity induced by (Cd). Twenty rats were equally divided into four groups: control group, Cd group treated with 15 mg/kg b.wt CdCl2, CLO administered 200 CLO, Cd+CLO group. All groups orally for 4 weeks. Cadmium (Cd) exposure caused anemia damage, evidenced increased serum levels urea, creatinine, uric acid, total bilirubin (including its direct indirect fractions), elevated activities liver enzymes such alanine transaminase (ALT), aspartate (AST), alkaline phosphatase (ALP). However, protein albumin decreased. Furthermore, there was decrease glutathione, glutathione transferase, catalase antioxidant profiles. Meanwhile, malondialdehyde increased. expression apoptosis markers, tumor necrosis factor-alpha (TNF-α) caspase-3, inflammation. ameliorated through decreasing urea (27.4%), creatinine (41.6%), enzymes, hepatic apoptotic markers while increasing protein, albumin, values SOD (60.37%), CAT (64.49%), GSH (50.41%), GST (9.16%). Hematological biochemical parameters, well system, improved following treatment, leading reduction damage. Therefore, is possible conclude that protects from inflammation, apoptosis, damage poisoning. Comprehensive translational research required validate CLO's efficacy safety use humans. Future studies should focus on elucidating precise molecular mechanisms, optimal dosing strategies, potential synergistic other therapeutic agents.

Язык: Английский

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Effect of dietary quercetin supplementation on high-starch diet-induced growth impairment, metabolic dysregulation, and oxidative stress in largemouth bass (Micropterus salmoides)

Aquaculture Reports, Год журнала: 2025, Номер 41, С. 102704 - 102704

Опубликована: Фев. 20, 2025

Язык: Английский

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Autophagy protects against Cd-induced cell damage in primary chicken hepatocytes via mitigation of oxidative stress and endoplasmic reticulum stress

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 259, С. 115056 - 115056

Опубликована: Май 23, 2023

Cadmium (Cd) is widespread globally in the environment as a toxic metal. Although it well known to induce hepatotoxicity cells, defense mechanisms against detrimental effects of Cd are still unknown. We examined role autophagy (a cellular mechanism) on Cd-induced cytotoxicity bird hepatocytes. Primary chicken hepatocytes were cultured with different concentrations (0, 1, 2.5, 5, and 10 μM) cadmium chloride (CdCl2) for 12 h. assessed CdCl2 cell viability, antioxidant status, reactive oxygen species (ROS) generation, response endoplasmic reticulum (ER) stress. Further, also evaluated that insight into underling molecular involved study. In this study, CdCl2-induce was caused by drastically increased ROS generation reduction level enzymes. It demonstrated marked activation ER stress markers (GRP78, IRE1, PERK, ATF4, ATF6 XBP-1 s) observed. Simultaneously, low-dose (1 exposed group observed, but high-dose (10 inhibited significantly promoted apoptosis, indicated expression related genes P62, Beclin-1, ATG3, ATG5, ATG9, detection autophagic vacuoles. Pretreatment agonist Rapamycin (RAP) has successfully reduced production, attenuated enhanced while inhibitor 3-Methyladenine (3-MA) had opposite effect. Hence, these findings stipulate could inhibit viability dose-dependent manner. Autophagy relieves via reducing regulating identified novel protective mechanism Cd-mediated hepatotoxicity.

Язык: Английский

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Exploration of the protective mechanisms of Icariin against cisplatin-induced renal cell damage in canines

Frontiers in Veterinary Science, Год журнала: 2024, Номер 11

Опубликована: Фев. 21, 2024

This study delves into the protective mechanisms of Icariin (ICA) against cisplatin-induced damage in Madin-Darby canine kidney (MDCK) cells. Comprising two distinct phases, investigation initially employed a single-factor randomized design to ascertain minimal cisplatin concentration eliciting MDCK cell damage, spanning concentrations from 0 16 mmol/L. Concurrently, various ICA (ranging 5 50 mmol/L) were combined with 1 mmol/L determine most efficacious treatment concentration. Subsequent investigations utilized four groups: control, cisplatin, + 20 ICA, and 25 aimed at elucidating ICA's mechanisms. Findings initial phase underscored significant reduction viability comparison control ( P < 0.01). Notably, inclusion substantively ameliorated under Moreover, administration induced an elevation inflammatory factors, malondialdehyde (MDA), reactive oxygen species (ROS), Bax protein levels, while concurrently suppressing superoxide dismutase (SOD), catalase (CAT), Bcl-2 expression Conversely, supplementation demonstrated marked increase mitochondrial membrane potential levels SOD, CAT, These interventions effectively attenuated responses suppressed 0.05), consequently mitigating apoptosis cells In summary, these findings elucidate role impeding by regulating responses, oxidative stress, autophagic expression.

Язык: Английский

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Asperuloside attenuates cadmium-induced toxicity by inhibiting oxidative stress, inflammation, fibrosis and apoptosis in rats

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Апрель 7, 2023

Abstract This present study investigated the protective effects of asperuloside (ASP) against cadmium-induced nephrocardiac toxicity. Rats were treated with 50 mg/kg ASP for five weeks and CdCl 2 (5 mg/kg, p.o., once daily) during last 4 treatment. The serum levels blood urea nitrogen (BUN), creatinine (Scr), aspartate transaminase (AST), creatine kinase-MB (CK-MB), troponin T (TnT) lactate dehydrogenase (LDH) evealuted. Oxido-inflammatory parameters detected via malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β) nuclear kappa B (NF-κB) . Additionally, cardiorenal caspase 3, transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), collagen IV Bcl2 measured by ELISA or immunohistochemical assays. results indicated that significantly decreased Cd-instigated oxidative stress, BUN, Scr, AST, CK-MB, TnT LDH as well histopathological alterations. Furthermore, notably attenuated Cd-induced apoptosis fibrosis reducing 3 TGF-β levels, stain intensity a-SMA IV, while increasing intensity. These revealed Cd induced cardiac renal toxicity which may be attributed to inflammation, apoptosis.

Язык: Английский

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