Inhibition of cisplatin-induced Acsl4-mediated ferroptosis alleviated ovarian injury

Wang, Siyuan; Li, Xuqing; Li, Jun; Wang, Aiping; Li, Fangfang; Hu, Huiqing; Long, Tengfei; Pei, Xueting; Li, Hongyan; Zhong, Fei; Zhu, Fengyu

doi:10.1016/j.cbi.2023.110825

Cited by 5 publications

(1 citation statement)

References 47 publications

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“…Recent studies have highlighted the significant role of ferroptosis in the treatment of chemotherapy-induced ovarian dysfunction [ 11 , 12 ]. Chemotherapy drugs induce iron accumulation in ovarian tissues, leading to increased oxidative stress and damage to ovarian function [ 13 ]. Furthermore, excess iron can induce apoptosis in ovarian cells, affecting normal ovarian function [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Zhou,

Huang,

Zeng

et al. 2024

J Ovarian Res

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Background Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy. Methods hUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells. Results hUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells. Conclusion hUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.

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Section: Introductionmentioning

confidence: 99%

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Zhou,

Huang,

Zeng

et al. 2024

J Ovarian Res

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Rosiglitazone retards the progression of iron overload-induced osteoarthritis by impeding chondrocyte ferroptosis

Cao,

Wei,

Yue

et al. 2024

iScience

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Icariin alleviates cisplatin-induced premature ovarian failure by inhibiting ferroptosis through activation of the Nrf2/ARE pathway

Li,

Zhu,

Wang

et al. 2024

Sci Rep

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Cisplatin is a widely used chemotherapeutic drug that can induce ovarian damage. Icariin (ICA), a natural antioxidant derived from Epimedium brevicornum Maxim. , has been found to protect against organ injury. The aim of the present study was to investigate whether ICA can exert an ovarian-protective effect on cisplatin induced premature ovarian failure (POF) and the underlying mechanism involved. The preventive effect of ICA was evaluated using body weight, the oestrous cycle, ovarian histological analysis, and follicle counting. ICA treatment increased body weight, ovarian weight, and the number of follicles and improved the oestrous cycle in POF mice. ICA reduced cisplatin-induced oxidative damage and upregulated the protein expression levels of Nrf2, GPX4 and HO-1. Moreover, ICA reduced the expression levels of Bax and γH2AX and inhibited ovarian apoptosis. In addition, ICA activated the Nrf2 pathway in vitro and reversed changes in the viability of cisplatin-induced KGN cells, reactive oxygen species (ROS) levels, lipid peroxidation, and apoptosis, and these effects were abrogated when Nrf2 was knocked down or inhibited. Molecular docking confirmed that ICA promotes the release of Nrf2 by competing with Nrf2 for binding to Keap1. The inhibitory effects of ICA on cisplatin-induced oxidative stress, ferroptosis, and apoptosis may be mediated by its modulatory effects on the Nrf2 pathway, providing a novel perspective on the potential mechanisms by which ICA prevents POF.

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Inhibition of cisplatin-induced Acsl4-mediated ferroptosis alleviated ovarian injury

Cited by 5 publications

References 47 publications

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Rosiglitazone retards the progression of iron overload-induced osteoarthritis by impeding chondrocyte ferroptosis

Icariin alleviates cisplatin-induced premature ovarian failure by inhibiting ferroptosis through activation of the Nrf2/ARE pathway

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