Protective properties of glycogen synthase kinase-3 inhibition against doxorubicin-induced oxidative damage to mouse ovarian reserve

Niringiyumukiza, Jean Damascene; Cai, Hong-Cai; Chen, Li; Li, Yamin; Wang, Lingjuan; Zhang, Mengdi; Xu, Xiaoyan; Xiang, Wenpei

doi:10.1016/j.biopha.2019.108963

Cited by 24 publications

(18 citation statements)

References 68 publications

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“…Here, the activities of the antioxidative enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) and the contents of the small molecules glutathione (GSH), ROS, and malondialdehyde (MDA) were used to assess oxidative stress levels in tissues or cells [31,32,33]. TNF-α, interleukin (IL)-6, and IL-10 were used to evaluate the degree of inflammation.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival

Jiang

Zhao-yuan

Cha

et al. 2019

IJMS

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This study was designed to investigate the protective effect of resveratrol (RES) on premature ovarian failure (POF) and the proliferation of female germline stem cells (FGSCs) at the tissue and cell levels. POF mice were lavaged with RES, and POF ovaries were co-cultured with RES and/or GANT61 in vitro. FGSCs were pretreated with Busulfan and RES and/or GANT61 and co-cultured with M1 macrophages, which were pretreated with RES. The weights of mice and their ovaries, as well as their follicle number, were measured. Ovarian function, antioxidative stress, inflammation, and FGSCs survival were evaluated. RES significantly increased the weights of POF mice and their ovaries as well as the number of follicles, while it decreased the atresia rate of follicles. Higher levels of Mvh, Oct4, SOD2, GPx, and CAT were detected after treatment with RES in vivo and in vitro. RES treatment resulted in significantly lower TNF-α and IL-6 concentrations and an obviously higher IL-10 concentration in the ovaries. In FGSCs, higher Mvh, Oct4, and SOD2 concentrations and lower TNF-α, IL-6, and MDA concentrations were measured in the RES group. Blockage of the Hh signaling pathway reversed the protective effect of RES on FGSCs. In conclusion, RES effectively improved the ovarian function of the POF model and the productive capacity of FGSCs via relieving oxidative stress and inflammation and a mechanism involving the Hh signaling pathway, suggesting that RES is a potential agent against POF and can aid in the survival of FGSCs.

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Section: Introductionmentioning

confidence: 99%

Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival

Jiang

Zhao-yuan

Cha

et al. 2019

IJMS

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“…In addition, Nrf2 exerts the protective mechanism by regulating expressions of Nrf2 downstream target genes (including HO-1, CAT, SOD, and GSTM1) in cryopreserved OTs. Many studies found that MLT is a potent regulator of Nrf2 and HO-1 in oxidative damage ( Kang et al, 2018 ; Niringiyumukiza et al, 2019 ). Therefore, it can be assumed that restraint stress can achieve oxidative stress by interfering with the Nrf2/HO-1 signaling pathway in cryopreserved OTs.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

Sun

Liu

Yang

et al. 2020

Front. Mol. Biosci.

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In the field of assisted reproductive technology, female fertility preservation, particularly ovarian tissue cryopreservation in adolescent cancer patients, has attracted much attention. Melatonin (MLT) is well known for its antioxidative and anti-apoptotic properties; however, whether it can ameliorate the cryoinjury and inhibit the generation of reactive oxygen species (ROS) in cryopreserved ovarian tissues (OTs) has not yet been reported. Here, we demonstrated that MLT could protect follicular integrity; prevent cell apoptosis; decrease ROS, malondialdehyde (MDA), and nitric oxide (NO) levels; and increase activities of glutathione peroxidases (GSH-Px), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) in cryopreserved OTs. Furthermore, these effects may be related with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, as evidenced by increased mRNA levels of Nrf2 downstream genes, including heme oxygenase-1 (HO-1), glutathione S-transferase M1 (GSTM1), SOD, and CAT. In summary, MLT can not only directly scavenge ROS but also significantly induce the activation of antioxidative enzymes via the Nrf2 signaling pathway, which is a new mechanism underlying the protection effects of MLT on cryopreserved OTs.

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“…This apoptosis results from double‐strand breaks caused by the ATM/ABL/TAp63 pathway in mice xenografted with human ovarian tissue [21]. Oxidative damage may also be involved in the ovarian damage caused by DOX [23].…”

Section: Mechanisms Involved In Premature Ovarian Failure After Cytotoxic Treatmentmentioning

confidence: 99%

“…Nrf2 expression and synthesis levels were also higher in cotreated mice. In parallel, PF counts were higher in cotreated mice than in mice treated with DOX alone [23].…”

Section: Evidence That Some Anticancer Treatments Can Protect the Ovarian Reservementioning

confidence: 99%

Can Some Anticancer Treatments Preserve the Ovarian Reserve?

et al. 2021

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Background Preventing premature ovarian failure (POF) is a major challenge in oncology. With conventional regimens, cytotoxicity‐associated POF involves primordial follicles (PF) pool depletion by apoptosis or overactivation mechanisms, notably mediated by the ABL/TAp63 and PI3K/Akt/mTOR pathways. New anticancer treatments have been designed to target pathways implicated in tumor growth. Although concerns regarding fertility arise with these targeted therapies, we hypothesized that targeted therapies may exert off‐tumor effects on PF that might delay POF. We provide an overview of evidence concerning these off‐tumor effects on PF. Limitations and future potential implications of these findings are discussed. Design PubMed was searched by combining Boolean operators with the following keywords: fertility, ovarian, follicle, anti‐tumoral, cancer, targeted, cytotoxic, and chemotherapy. Results Cisplatin‐related PF apoptosis via the ABL/TAp63 pathway was targeted with a tyrosine kinase inhibitor, imatinib, in mice, but effects were recently challenged by findings on human ovarian xenografts in mice. In cyclophosphamide‐treated mice, PI3K/Akt/mTOR pathway inhibition with mTOR inhibitors and AS101 preserved the PF pool. Proteasome and GSK3 inhibitors were evaluated for direct and indirect follicle DNA damage prevention. Surprisingly, evidence for cytotoxic drug association with PF pool preservation was found. We also describe selected non‐anticancer molecules that may minimize gonadotoxicity. Conclusion Not all anticancer treatments are associated with POF, particularly since the advent of targeted therapies. The feasibility of associating a protective drug targeting PF exhaustion mechanisms with cytotoxic treatments should be evaluated, as a way of decreasing the need for conventional fertility preservation techniques. Further evaluations are required for transfer into clinical practice. Implications for Practice Anticancer therapies are associated with infertility in 10%–70% of patients, which is the result of primordial follicles pool depletion. Alone or associated with gonadotoxic treatments, some targeted therapies may exert favorable off‐targets effects on the primordial follicle pool by slowing down their exhaustion. Current evidence of these effects relies on murine models or human in vitro models. Evaluation of these protective strategies in humans is challenging; however, if these results are confirmed with clinical and biological data, it not only could be a new approach to female fertility preservation but also would change standard fertility strategies.

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Protective properties of glycogen synthase kinase-3 inhibition against doxorubicin-induced oxidative damage to mouse ovarian reserve

Cited by 24 publications

References 68 publications

Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival

Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival

Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

Can Some Anticancer Treatments Preserve the Ovarian Reserve?

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