Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9205 - 9205

Published: May 24, 2023

Granulosa cells are essential for follicle initiation and development, their abnormal function or apoptosis is a crucial factor leading to follicular atresia. A state of oxidative stress occurs when the balance between production reactive oxygen species regulation antioxidant system disturbed. Oxidative one most important causes granulosa cells. in female reproductive diseases, such as polycystic ovary syndrome premature ovarian failure. In recent years, studies have confirmed that mechanism closely linked PI3K-AKT signaling pathway, MAPK FOXO axis, Nrf2 NF-κB mitophagy. It has been found drugs sulforaphane, Periplaneta americana peptide, resveratrol can mitigate functional damage caused by on This paper reviews some mechanisms involved describes underlying pharmacological treatment

Language: Английский

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The emerging role of ferroptosis in female reproductive disorders

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115415 - 115415

Published: Sept. 4, 2023

Iron, as an essential trace element for the organism, is vital maintaining organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis a novel form of programmed cell death distinguished by overload lipid peroxidation, which unique from autophagy, apoptosis necrosis, more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis associated with development female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), cancer (OC), preeclampsia (PE) spontaneous abortion (SA). Pathways genes may participate in processes regulate granulosa proliferation secretion, oocyte development, reserve function, early embryonic placental oxidative stress. However, its exact mechanism has not been fully revealed. Therefore, our review systematically elaborates occurrence research progress FRDs, view to providing literature references clinical targeting -related pathways regulatory factors management FRDs.

Language: Английский

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Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 334 - 334

Published: Feb. 26, 2025

In recent years, ferroptosis, as an emerging modality of programmed cell death, has captured significant attention within the scientific community. This comprehensive review meticulously canvasses pertinent literature past few spanning multiple facets. It delves into intricate mechanisms underpinning tracks evolution its inducers and inhibitors, dissects roles in a diverse array diseases, well resultant therapeutic implications. A profound exploration is conducted functional ferroptosis-related molecules, intracellular pathways, metabolic cascades, signaling transduction routes. Novel ferroptosis inhibitors are introduced detail, covering their design blueprints, synthetic methodologies, bioactivity profiles. Moreover, exhaustive account provided regarding involvement malignancies, neurodegenerative disorders, cardiovascular ailments, other pathologies. By highlighting pivotal status potential regimens various this aspires to furnish thorough reference framework for future investigations clinical translations domain.

Language: Английский

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Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(6)

Published: May 18, 2023

Abstract The relationship of obesity and osteoporosis has been widely studied over the past years. However, implications for bone health remain controversial, underlying molecular mechanism is not yet fully understood. This study demonstrated that high‐fat diet‐induced leads to significantly decreased volume/tissue volume (BV/TV), trabecular number (Tb.N), cortical thickness (Ct.Th) male rat femur after mechanical loading effects body weight were controlled. HFD‐induced obese rats exhibited attenuated expression ferroptosis inhibitory protein SLC7A11 GPX4 in tissues, which was correlated with elevated serum TNF‐α concentration. Ferroptosis inhibitor administration could effectively rescue osteogenesis‐associated type H vessels osteoprogenitors, downregulate levels ameliorate loss rats. Since both affect vessel formation, we further investigated interaction between TNF‐α, its impact osteogenesis angiogenesis vitro. In human osteoblast‐like MG63 umbilical vein endothelial cells (HUVEC), TNF‐α/TNFR2 signaling promoted cystine uptake GSH biosynthesis provide protection against low‐dose inducer erastin. While, TNF‐α/TNFR1 facilitated presence high‐dose erastin through ROS accumulation. Moreover, regulated ferroptosis‐induced osteogenic angiogenic dysfunctions based on regulatory role. Meanwhile, inhibitors reduce intracellular overproduction enhance TNF‐α‐treated HUVECs. revealed angiogenesis, provides new insights into pathogenesis regenerative therapy obesity‐related osteoporosis.

Language: Английский

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From Pathophysiology to Treatment: The Role of Ferroptosis in PCOS

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 17, 2025

Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10-13%. The etiology PCOS multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, dysregulation. Iron, critical mineral, not only plays role regulating female physiological functions the progression but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, form nonapoptotic cell death characterized by accumulation lipid peroxides. While numerous studies have explored ferroptosis patients animal models, precise mechanisms therapeutic implications remain inadequately understood. This review seeks elucidate pathophysiology contributory factors ferroptosis. Additionally, we examine diverse manifestations evaluate its role. Furthermore, introduce ferroptosis-related traditional Chinese medicines that may enhance understanding pathogenesis aid development targeted therapies for PCOS.

Language: Английский

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Targeting ferroptosis for the treatment of female reproductive system disorders

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

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Neratinib inhibits proliferation and promotes apoptosis of acute myeloid leukemia cells by activating autophagy‐dependent ferroptosis

Drug Development Research, Journal Year: 2022, Volume and Issue: 83(7), P. 1641 - 1653

Published: Aug. 28, 2022

Acute myeloid leukemia (AML) is a hematologic malignancy with increased lethality. We focused on elucidating the role of Neratinib, tyrosine kinase inhibitor, in progression AML and identify potential mechanisms. Upon treatment autophagy suppressor 3-methyladenine (3-MA) ferroptosis stimulator Erastin, viability proliferation HL-60 cells were evaluated by cell counting kit-8 5-Ethynyl-20-Deoxyuridine staining assays. A flow cytometer was to observe cycle apoptosis. Production reactive oxygen species (ROS) tested via 2,7-dichlorodihydrofluorescein diacetate assay. Additionally, malondialdehyde (MDA) content Fe2+ activity examined commercial kits. LC3-II expression using immunofluoresence staining. Western blot analysis ascertained proliferation, apoptosis, autophagy-associated proteins. It noted that Neratinib notably mitigated cut down Ki67 proliferating nuclear antigen expression. Moreover, hindered at G0/G1 phase whereas exacerbated ROS, MDA activities elevated coupled reduced glutathione peroxidase 4, ferritin heavy chain 1 enhanced acyl-CoA synthetase long-chain family member 4 Furthermore, promoted cells, evidenced raised LC3-II, ATG5, Beclin1 lessened p62 Importantly, 3-MA eased impacts ferroptosis, which offset further administration Erastin. To conclude, could suppress promote apoptosis through autophagy-dependent ferroptosis.

Language: Английский

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Current Understanding of and Future Directions for Endometriosis-Related Infertility Research with a Focus on Ferroptosis

Diagnostics, Journal Year: 2023, Volume and Issue: 13(11), P. 1926 - 1926

Published: May 31, 2023

To date, the development of therapy for endometriosis and disease-related infertility remains a major challenge. Iron overload caused by periodic bleeding is hallmark endometriosis. Ferroptosis an iron- lipid-reactive oxygen species-dependent type programmed cell death that distinct from apoptosis, necrosis, autophagy. This review summarizes current understanding future directions research treatment infertility, with main focus on molecular basis ferroptosis in endometriotic granulosa cells. Papers published between 2000 2022 PubMed Google Scholar databases were included this review. Emerging evidence suggests closely linked to pathophysiology Endometriotic cells are characterized resistance, whereas remain highly susceptible ferroptosis, suggesting regulation utilized as interventional target into infertility. New therapeutic strategies urgently needed efficiently kill while protecting An analysis pathway vitro, vivo, animal enhances our pathogenesis disease. Here, we discuss role modulators approach potential novel

Language: Английский

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Perfluorooctane sulfonate (PFOS) and its selected analogs induce various cell death types in peripheral blood mononuclear cells

Chemosphere, Journal Year: 2024, Volume and Issue: 354, P. 141664 - 141664

Published: March 12, 2024

Language: Английский

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Endometrial stem cells alleviate cisplatin-induced ferroptosis of granulosa cells by regulating Nrf2 expression

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 11, 2024

Abstract Background Premature ovarian failure (POF) caused by cisplatin is a severe and intractable sequela for young women with cancer who received chemotherapy. Cisplatin causes the dysfunction of granulosa cells mainly leads to but not limited its apoptosis autophagy. Ferroptosis has been also reported participate, while little known about it. Our previous experiment demonstrated that endometrial stem (EnSCs) can repair cisplatin-injured cells. However, it still unclear whether EnSCs play role acting on ferroptosis. Methods Western blotting quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were applied detect expression levels ferroptosis-related genes. CCK-8 5-Ethynyl-2’-deoxyuridine (EdU) assays used evaluate cell viability. Transmission electron microscopy (TEM) was performed ferroptosis in morphology. And extent assessed ROS, GPx, GSSG MDA indicators. In vivo, morphology presented HE staining protein tissue detected immunohistochemistry. Results results showed could occur inhibitor ferrostatin-1 (Fer-1) partly restored viability mitigated damage inhibiting Moreover, potential be markedly blocked ML385. Conclusion study induce cells, inhibit thus exert effects cisplatin-induced injury model both vivo vitro. Meanwhile, Nrf2 validated participate this regulatory process played an essential role.

Language: Английский

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