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

Circ_0000284 Is Involved in Arsenite-Induced Hepatic Insulin Resistance Through Blocking the Plasma Membrane Translocation of GLUT4 in Hepatocytes via IGF2BP2/PPAR-γ DOI Creative Commons
Shiqing Xu, Zhiping Hu, Yujie Wang

и другие.

Toxics, Год журнала: 2024, Номер 12(12), С. 883 - 883

Опубликована: Дек. 4, 2024

Arsenic exposure can induce liver insulin resistance (IR) and diabetes (DM), but the underlying mechanisms are not yet clear. Circular RNAs (circRNAs) involved in regulation of onset diabetes, especially progression IR. This study aimed to investigate role circRNAs arsenic-induced hepatic IR its mechanism. Male C57BL/6J mice were given drinking water containing sodium arsenite (0, 0.5, 5, or 50 ppm) for 12 months. The results show that increased circ_0000284 expression, decreased insulin-like growth factor 2 mRNA binding protein (IGF2BP2) peroxisome proliferator-activated receptor-γ (PPAR-γ), inhibited cell membrane levels insulin-responsive glucose transporter 4 (GLUT4) mouse livers, indicating arsenic causes damage disruptions metabolism. Furthermore, reduced consumption glycogen levels, expression circ_0000284, IGF2BP2 PPAR-γ, GLUT4 membranes insulin-treated HepG2 cells. However, a inhibitor reversed exposure-induced reductions IGF2BP2, plasma membrane. These indicate is arsenite-induced through blocking translocation hepatocytes via IGF2BP2/PPAR-γ. provides scientific basis finding early biomarkers control type mellitus (T2DM), discovering new prevention measures.

Язык: Английский

Процитировано

1

Chitosan oligosaccharide alleviates DON-induced liver injury via suppressing ferroptosis in mice DOI Creative Commons
Mengjie Liu, Zhenlin Li, Jie Li

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 290, С. 117530 - 117530

Опубликована: Дек. 13, 2024

Язык: Английский

Процитировано

1

Resveratrol modulates ferroptosis: Promising therapeutic targets in ischemia-reperfusion DOI Creative Commons
Guangming Zeng,

Jingwen Liang,

Jie Xiang

и другие.

Journal of Functional Foods, Год журнала: 2024, Номер 122, С. 106520 - 106520

Опубликована: Окт. 23, 2024

Язык: Английский

Процитировано

0

Investigation of Possible Protective Effects of Resveratrol on Oxidative Stress and Ferroptosis in PFOA Exposure in HepG-2 Cells DOI Open Access
Didem Oral, Ceyhan Hacıoğlu

Konuralp Tıp Dergisi, Год журнала: 2024, Номер unknown

Опубликована: Сен. 10, 2024

Objective: Exposure to perfluorooctanoic acid (PFOA) is linked adverse health effects, including cancer and hepatic diseases. PFOA induces reactive oxygen species generation in human cells, causing oxidative stress cell death. Resveratrol (RSV) has garnered attention for its protective effects against xenobiotic-induced damage, yet impact on PFOA-induced ferroptosis the liver remains understudied. This study investigates RSV's mechanisms HepG2 cells exposed PFOA. Method: were cultured DMEM with 10% FBS 1% penicillin/streptomycin a 5% CO2 incubator at 37°C. was added concentrations ranging from 0 450 µM incubated 37°C 24 hours. The IC50 determined be 457 μM. To examine treated 60 μM RSV. Following treatment PFOA, RSV, combination of PFOA+RSV, lysates prepared analysis. Oxidative parameters measured spectrophotometrically using ELISA. Results: In PFOA+RSV group, antioxidant capacity increased, suppressed compared control. Conversely, group showed decreased capacity, increased oxidant induced control RSV-treated groups. Conclusion: exposure heightens ferroptosis, whereas RSV significantly reduces protects during exposure.

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.

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

Процитировано

0