Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway DOI Creative Commons

Runtian Li,

Lintao Li, Haiyang Wu

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 580 - 580

Published: May 11, 2025

Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such enteropathy. Presently, there are limited options preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health benefits, but their antiradiation mechanisms not fully understood. C57BL/6 mice pre-treated with TP five days showed improvement survival rates after being exposed 10 Gy of 60Co radiation. In the same way, abdominal exposure 15 effectively mitigated radiation-induced colon shortening, damage tissues, oxidative stress, release inflammatory factors, and disruptions microbial balance. addition, treatment lowered elevation reactive oxygen species (ROS), iron imbalance, mitochondrial damage, ferroptosis IEC-6 cells post-irradiation. Utilizing network pharmacology, molecular docking, affinity testing, we identified that has capability target Nrf2/HO-1/GPX4 signaling pathway, while EGCG, principal constituent TP, interacts HSP90 mitigates ferroptosis. These findings suggest may serve promising therapeutic agent alleviate (RII).

Language: Английский

A Highly Potent Apomorphine Derivative Enhancing Neurite Outgrowth via Nrf2 Activation DOI Creative Commons
Tamaki Ishima, Hitoshi Osaka, Ryozo Nagai

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 537 - 537

Published: April 29, 2025

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related 2 (Nrf2) and exerts antioxidant effects, making it promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote neurite outgrowth in PC12 cells under nerve growth (NGF) stimulation. D55, an derivative, retains the hydroxyl group at APO’s 11th position while substituting 10th with ethoxy group. D55 exhibited highest potency (EC50 = 0.5661 nM), significantly enhancing outgrowth. demonstrated efficacy (Emax ~10-fold increase), edaravone (Eda) required higher concentrations 22.5 nM) moderate effects ~4-fold increase). D30, which was replaced methoxy group, had no effect. Neurite outgrowth-promoting APO, Eda were attenuated by Nrf2 siRNA knockdown, confirming that neuroplasticity are Nrf2-mediated. These findings confirm is highly potent Nrf2-activating compound strong neuroprotective potential, providing new insights into its therapeutic applications neurodegenerative diseases associated

Language: Английский

Citations

0
Calycosin alleviates ferroptosis and attenuates doxorubicin-induced myocardial injury via the Nrf2/SLC7A11/GPX4 signaling pathway DOI Creative Commons

Quancheng Han,

Jingle Shi,

Yiding Yu

et al.

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

Published: Nov. 12, 2024

Background Heart failure is primarily characterized by damage to the structure and function of heart. Ferroptosis represents a form programmed cell death, studies indicate that it constitutes one primary mechanisms underlying cardiomyocyte death in heart failure. Calycosin, natural compound derived from astragalus, exhibits various pharmacological properties, including anti-ferroptosis, antioxidant effects, cardiovascular protection. Nonetheless, specific role Calycosin treatment ferroptosis remains poorly understood. Objective This study aims elucidate regulatory effect on its influence through vivo vitro experiments. Methods A rat model was induced using doxorubicin, cardiac evaluated ultrasound examination NT-Pro BNP detection. Myocardial injury assessed H&E staining Masson staining. The extent mitochondrial transmission electron microscopy. Concurrently, level analyzed measuring markers, MDA, ferrous ions, GSH/GSSG ratio, GPX4 activity. Subsequently, molecular mechanism which exerts therapeutic effects investigated immunofluorescence Western blotting. Finally, H9c2 cardiomyocytes were treated with doxorubicin simulate myocardial injury, mediates further verified Nrf2 gene silencing. Results significantly improves rats, reduces serum levels, alleviates damage. Additionally, decreases levels tissue, as confirmed microscopy assessment GSH, At level, activating Nrf2/SLC7A11/GPX4 signaling pathway, evidenced upregulation Nrf2, SLC7A11, GPX4, GSS, GCL protein expression. process substantially enhances capacity tissue effectively suppresses cells. results obtained both experiments are consistent. Notably, when silenced, protective myocardium markedly diminished. Conclusion treats doxorubicin-induced likely closely associated activation pathway inhibition Consequently, promising against cardiotoxicity, warrants investigation.

Language: Английский

Citations

3
Hippocampal microRNA-181a overexpression participates in anxiety and ethanol related behaviors via regulating the expression of SIRT-1 DOI
Amine Bahí

Physiology & Behavior, Journal Year: 2025, Volume and Issue: unknown, P. 114839 - 114839

Published: Feb. 1, 2025

Language: Английский

Citations

0
Systemic DNA damage in Brazilian farmers exposed to pesticides DOI Creative Commons

Melissa Mancini,

Maria Eduarda Vieira Cerny,

Natali S. Cardoso

et al.

Academia molecular biology and genomics., Journal Year: 2025, Volume and Issue: 2(1)

Published: March 21, 2025

The chronic health effects of pesticides exposure include reproductive damage, neurological hormonal dysfunction, and cancer; the genotoxic are primary factor contributing to carcinogenesis. To measure DNA two techniques have stood out for risk analysis in exposed populations: comet assay cytokinesis-blocked micronucleus (CBMN) technique. Therefore, we conducted a review published articles on damage Brazilian farmers pesticides, with aim finding whether our at increased problems. period covered by studies was from Jan 2009 Dec 2024. After undergoing thorough selection, fourteen composed final analysis, totaling 801 708 controls. In means comparison between control groups, first heterogeneity assessment made, which indicated strong (I2) both tails length (tl) (I2 = 91.6%; p <0.001) frequency micronuclei 92.8%; <0.001), so chose random model analysis. When comparing obtained assay, absolute difference (WMD) 14.388, <0.001. Increased values measured CBMN assays were observed most included this review, found higher compared controls applying meta-analysis results studied articles.

Language: Английский

Citations

0
Prenatal Exposure To Valproic Acid Induces Increased Autism-Like Behaviors and Impairment of Learning and Memory Functions in Rat Offspring by Upregulating ADAM10 Expression DOI Creative Commons
Jingyuan Yang, Xiaoli Li,

Jing Tan

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(3)

Published: April 17, 2025

Autism spectrum disorder (ASD) involves a complex neurodevelopmental pathogenesis. A disintegrin and metalloproteinase 10 (ADAM10) plays crucial role in embryonic brain development neural network stability. This study aimed to investigate the influence of ADAM10 on excitation/inhibition (E/I) balance, autism-like behaviors, learning memory dysfunction rats prenatally exposed valproic acid (VPA) determine potential intervention strategies. The VPA-exposed group exhibited increased levels secreted amyloid precursor protein-α (sAPPα). Moreover, overexpression glutamate decarboxylase 1 N-methyl-D-aspartate receptors was observed. High-performance liquid chromatography-mass spectrometry revealed elevated glutamate, glutamine, γ-aminobutyric acid, as well an E/I imbalance VPA group. Additionally, narrower synaptic clefts postsynaptic density vesicles were Remarkably, intraperitoneal administration inhibitor during critical period significantly improved ASD-like behavior function rats. effectively reduced abnormally high sAPPα prefrontal cortex corrected abnormal balance. Thus, inhibiting may improve imbalance, alleviate core symptoms ASD, dysfunction. use represents therapeutic strategy for treating ASD patients with intellectual disabilities.

Language: Английский

Citations

0
Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway DOI Creative Commons

Runtian Li,

Lintao Li, Haiyang Wu

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 580 - 580

Published: May 11, 2025

Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such enteropathy. Presently, there are limited options preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health benefits, but their antiradiation mechanisms not fully understood. C57BL/6 mice pre-treated with TP five days showed improvement survival rates after being exposed 10 Gy of 60Co radiation. In the same way, abdominal exposure 15 effectively mitigated radiation-induced colon shortening, damage tissues, oxidative stress, release inflammatory factors, and disruptions microbial balance. addition, treatment lowered elevation reactive oxygen species (ROS), iron imbalance, mitochondrial damage, ferroptosis IEC-6 cells post-irradiation. Utilizing network pharmacology, molecular docking, affinity testing, we identified that has capability target Nrf2/HO-1/GPX4 signaling pathway, while EGCG, principal constituent TP, interacts HSP90 mitigates ferroptosis. These findings suggest may serve promising therapeutic agent alleviate (RII).

Language: Английский

Citations

0