Resveratrol alleviates testicular toxicity induced by anti-PD-1 through regulating the NRF2-SLC7A11-GPX4 pathway DOI Creative Commons
Halahati Tuerxun, Yixin Zhao, Yawen Li

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Abstract Background: Fertility preservation is a critical concern for reproductive-age cancer survivors, as conventional cytotoxic therapies can cause irreversible damage to the reproductive system, potentially depriving them of ability have children in future. Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 (anti-PD-1), become standard therapeutic approach various malignancies. However, impact ICIs on function and fertility not well understood remains largely unexplored domain. Methods: Male C57BL6/J mice with B16 melanoma were assigned into four groups: control , anti-PD-1 (ICI) RSV, RSV (ICI/RSV) group. ICI/RSV groups received (40 mg/kg) orally every other day one month, while controls vehicle. ICI injected antibody (10 weekly, IgG2b kappa antibody. Parameters like body testicular weight, sperm concentration, Western blotting ferroptosis markers measured. Furthermore, oxidative stress biomarkers, lipid oxidation factors, gonadal hormone levels quantified using commercial kits. Results: Anti-PD-1 therapy caused male dysfunction, evidenced by reduced altered levels, disruption blood-testis barrier (BTB) integrity. was key mechanism anti-PD-1-induced characterized disrupted iron homeostasis, elevated peroxidation, suppression system Xc−/glutathione peroxidase 4 (GPX4) axis. Additionally, therapy diminished antioxidant defenses inhibiting nuclear factor erythroid 2-related 2 (NRF2) pathway, thereby increasing susceptibility ferroptosis. Crucially, treatment ameliorated dysfunction. This achieved reducing T infiltration, lowering interferon-gamma activating NRF2 maintainingiron homeostasis. Conclusions: Our study demonstrates that anti-PD-1triggers testis, causing Resveratrol may offer protection against toxicity associated anti-PD-1, particularly through its anti-ferroptosis properties.

Язык: Английский

Resveratrol Reorganizes the Impaired Cellular Functions of ARPE-19 Cells Created in Diabetes Model DOI Open Access
Mehmet Argun, Ömer Çelik

Online Türk Sağlık Bilimleri Dergisi, Год журнала: 2025, Номер 10(1), С. 38 - 44

Опубликована: Март 10, 2025

Objective: It is well known that high blood glucose levels can damage many visual functions. So, the study aimed to investigate effects of resveratrol on cellular lipid peroxidation (MDA), cytokines, VEGF-A and apoptosis in vitro diabetes model-induced ARPE-19 cells. Materials Methods: Six experimental groups were conceptualized as follows. 1-Control group: Received no treatment (Standard Growth Medium), 2-Mannitol Group (M): Cells incubated 19.5 mM Mannitol supplemented medium, 3-High Glucose (HG): (25 Glucose), 4-Resveratrol (R): with 100 µM Standard Medium, 5-Mannitol + Resveratrol (M+R), 6-High (HG+R). In All groups, cells for 48 hrs, MDA, IL-1β, TNF-α, Apoptosis measured. Results: High medium increased TNF-α while caused a significant decrement As result, prevented against related impaired conditions. Conclusions: conclusion, reverse disrupted functions by reducing oxidative stress supporting viability.

Язык: Английский

Процитировано

0
SIRT6 mitigates doxorubicin-induced cardiomyopathy via amelioration of mitochondrial dysfunction: A mechanistic study implicating the activation of the Nrf-2/FUNDC1 signaling axis DOI Creative Commons
Qi Wang, Hongshuo Shi,

Haowen Zhuang

и другие.

International Journal of Medical Sciences, Год журнала: 2025, Номер 22(7), С. 1640 - 1657

Опубликована: Фев. 28, 2025

Doxorubicin-induced myocardial injury, characterized by hypertrophy and heart failure (HF), represents a primary contributor to end-stage cardiovascular mortality associated with anthracycline drugs. Prior research has elucidated that SIRT6-mediated oxidative processes mitochondrial metabolic reprogramming are pivotal in sustaining energy metabolism during damage cardiomyocytes. In the aftermath of doxorubicin-induced fibrosis exacerbate impairment cardiac ejection function, resulting elevated oxygen consumption. This condition is accompanied disrupted ATP production, diminished biogenesis, inadequate synthesis new DNA, collectively triggering necroptosis apoptosis pathways. Our preliminary experimental results have confirmed SIRT6, traditional medicine, exerts cardioprotective effects. Nevertheless, interaction between SIRT6 Nrf-2-mediated biogenesis context HF remains inadequately understood. The generation mitochondria key mechanism involved DNA repair cell cycle management.

Язык: Английский

Процитировано

0
Resveratrol alleviates testicular toxicity induced by anti-PD-1 through regulating the NRF2-SLC7A11-GPX4 pathway DOI Creative Commons
Halahati Tuerxun, Yixin Zhao, Yawen Li

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 12, 2025

Background Fertility preservation is a critical concern for reproductive-age cancer survivors, as conventional cytotoxic therapies can cause irreversible damage to the reproductive system, potentially depriving them of ability have children in future. Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 (anti-PD-1), become standard therapeutic approach various malignancies. However, impact ICIs on function and fertility not well understood remains largely unexplored domain. Resveratrol (RSV), plant-derived compound, has shown potential an nuclear factor erythroid 2-related 2 (NRF2) agonist counteract toxicity induced by diseases, drugs, environmental toxins. Methods Male C57BL6/J mice with B16 melanoma were assigned into four groups. RSV ICI/RSV groups received (40 mg/kg) orally every other day one month, while controls vehicle. ICI injected anti-PD-1 antibody (10 weekly, IgG2b kappa antibody. Parameters like body testicular weight, sperm concentration, western blot ferroptosis markers measured. Furthermore, oxidative stress biomarkers, lipid oxidation factors, gonadal hormone levels quantified using commercial kits. Results Anti-PD-1 therapy caused male dysfunction, evidenced reduced altered levels, disruption blood-testis barrier (BTB) integrity. was key mechanism anti-PD-1-induced characterized disrupted iron homeostasis, elevated peroxidation, suppression system Xc−/glutathione peroxidase 4 (GPX4) axis. Additionally, diminished antioxidant defenses inhibiting NRF2 pathway, thereby increasing susceptibility ferroptosis. Crucially, treatment ameliorated dysfunction. This achieved reducing T infiltration, lowering interferon-gamma activating maintaining homeostasis. Conclusions Our study demonstrates that triggers testis, causing may offer protection against associated anti-PD-1, particularly through its anti-ferroptosis properties.

Язык: Английский

Процитировано

0
Natural Phenolic Compounds against Trichothecenes: From Protective Mechanisms to Future Perspectives DOI
Aimei Liu, Kan Zhu,

Chenchen Song

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Trichothecenes (TCNs), Fusarium-derived mycotoxins exemplified by deoxynivalenol and T-2 toxin, threaten global health through multisystem toxicity widespread contamination. Natural phenolic compounds (NPCs), leveraging their intrinsic safety natural abundance, demonstrate multimechanistic efficacy in counteracting TCN toxicity. This article reviews both domestic international research on the protective mechanisms of NPCs against TCN-induced exert effects multitiered mechanisms: (1) molecular regulation via Nrf2-centric antioxidant activation MAPK/NF-κB inflammatory axis suppression, coupled with coordinated inhibition programmed cell death pathways (apoptosis/ferroptosis/pyroptosis) autophagy modulation, where GPX4 emerges as a critical ferroptosis regulator; (2) restoring microbiome balance, enhancing intestinal barrier function, optimizing nutrient transport. Gut microflora may also serve an additional target for mitigating TCNs. further inhibit Fusarium proliferation mycotoxin biosynthesis. While there is demonstrated potential food sustainable feed development, challenges persist bioavailability optimization, pharmacokinetic profiling, microbiota-metabolite crosstalk. analysis advances NPC-based strategies detoxification agriculture.

Язык: Английский

Процитировано

0
DNA‐PKcs‐Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia‐Induced Cardiac Dysfunction in Type 1 Diabetes DOI Creative Commons
Junyan Wang, Xing Chang, Chun Li

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Abstract The DNA‐Dependent Protein Kinase catalytic subunit (DNA‐PKcs) acts as a principal executor in the DNA damage response (DDR), mediating phosphorylation of broad spectrum substrates integral to repair and apoptosis. This investigation seeks discern possible association mechanisms linking hyperglycemia‐induced ferroptosis DNA‐PKcs DCM. data exhibits substantial activation DNAPKcs‐ dependent DDR mice with streptozotocin‐induced However, deletion cardiomyocytes notably mitigates damage, enhances heart function dampens inflammatory response. Co‐IP/MS analysis subsequent validation experiments demonstrate that directly interacts phosphorylates YAP1 at Thr226. event facilitates nuclear retention YAP1, where it intensifies transcription ferroptosis‐associated genes. Knockin expressing nonphosphorylatable T226A mutant display decreased ferroptosis, reduced myocardial fibrosis improved function. Taken together, this study unravels an intracellular stress sensor, perceiving hyperglycemic conditions subsequently transmitting signal incite through interplay between YAP1. novel insight suggests DNA‐PKcs‐mediated could be promising therapeutic targets for management

Язык: Английский

Процитировано

0
Ponicidin Triggered Ferroptosis in Esophageal Squamous Cell Carcinoma by Suppressing the SLC7A11/Glutathione/GPX4 Signalling Axis DOI
Wenhu Liu, Jinhua Zhang, Min Wu

и другие.

Phytomedicine, Год журнала: 2025, Номер 143, С. 156925 - 156925

Опубликована: Май 28, 2025

Язык: Английский

Процитировано

0
Preparation of mitochondria-targeted gold nanoprobes and their SERS application in the detection of DON-induced apoptosis DOI
Zhiyi Song, Jinchi Han, Shuting Wang

и другие.

Analytical and Bioanalytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Июнь 3, 2025

Язык: Английский

Процитировано

0
Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review DOI
Pengju Wang,

Qin Yao,

Xiangwen Meng

и другие.

Food and Chemical Toxicology, Год журнала: 2023, Номер 182, С. 114121 - 114121

Опубликована: Окт. 26, 2023

Язык: Английский

Процитировано

6
Detoxification of DON-induced hepatotoxicity in mice by cold atmospheric plasma DOI Creative Commons
Ruonan Ma,

Yongqin Fan,

Xudong Yang

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 280, С. 116547 - 116547

Опубликована: Июнь 5, 2024

Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury humans animals. Cold atmospheric plasma (CAP) has received much attention mycotoxin degradation due to advantages easy operation, high efficiency, low temperature. So far, majority studies have focused on efficiency mechanism CAP DON, while there still little information available hepatotoxicity DON after treatment. Herein, this study aimed investigate effect DON-induced both vitro vivo its underlying mechanisms. The results showed that 120-s treatment achieved 97 % DON. L02 cells was significantly reduced with time. Meanwhile, markedly alleviated mice including balloon-like degeneration tissues elevation AST ALP level. for detoxification further elucidated. caused oxidative stress by suppressing antioxidant signaling pathway Nrf2/HO-1/NQO-1, consequently leading mitochondrial dysfunction cell apoptosis, accompanied cellular senescence inflammation. blocked inhibition Nrf2/HO-1/NQO-1 through efficient accordingly alleviating induced Therefore, an effective method eliminate hepatotoxicity, can be applied mycotoxin-contaminated feed ensure human animal health.

Язык: Английский

Процитировано

2
Therapeutic potential of resveratrol through ferroptosis modulation: insights and future directions in disease therapeutics DOI Creative Commons
Peng Liu, Xizhuo Hu, Zhiqiang Liu

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 25, 2024

Resveratrol, a naturally occurring polyphenolic compound, has captivated the scientific community with its promising therapeutic potential across spectrum of diseases. This review explores complex role resveratrol in modulating ferroptosis, newly identified form programmed cell death, and implications for managing cardiovascular cerebrovascular disorders, cancer, other conditions. Ferroptosis is intricately linked to pathogenesis diverse diseases, exerting multifaceted effects on this process. It mitigates ferroptosis by lipid peroxidation, iron accumulation, engaging specific cellular receptors, thereby manifesting profound benefits conditions, as well oncological settings. Moreover, resveratrol's capacity either suppress or induce through modulation signaling pathways, including Sirt1 Nrf2, unveils novel avenues. Despite limited bioavailability, advancements molecular modification drug delivery optimization have amplified clinical utility. Future investigations are poised unravel comprehensive mechanisms underpinning action expand repertoire. We hope could furnish detailed insight into exploration regulation prospects.

Язык: Английский

Процитировано

1