Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity

Ayres, Laura Silveira; Berger, Markus; Durli, Isabel Cirne Lima de Oliveira; Kuhl, Cristiana Palma; Terraciano, Paula Barros; Garcez, Tuane Nerissa Alves; Santos, Bruna Gomes dos; Guimarães, Jorge A.; Passos, Eduardo Pandolfi; Cirne-Lima, Elizabeth Obino

doi:10.1016/j.reprotox.2019.12.002

Cited by 13 publications

(15 citation statements)

References 31 publications

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“…Increased levels of TNF-α are considered to be one of the most important markers of increased inflammation [70]. In the present study, CP significantly increased pro-inflammatory (NF-κB, TNF-α, IL-1β, and IL-6) and significantly decreased the anti-inflammatory (IL-10) ovarian mRNA expression [37,71,72].…”

Section: Discussionsupporting

confidence: 58%

Melatonin Mitigates Cisplatin-Induced Ovarian Dysfunction via Altering Steroidogenesis, Inflammation, Apoptosis, Oxidative Stress, and PTEN/PI3K/Akt/mTOR/AMPK Signaling Pathway in Female Rats

et al. 2022

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Ovarian damage and fertility impairment are major side effects of chemotherapy in pre-menopausal cancer patients. Cisplatin is a widely used chemotherapeutic drug. The present study was designed to assess the ameliorative effects of melatonin as an adjuvant for fertility preservation. Thirty-two adult female Wistar rats were divided randomly into four equal groups: Control, Melatonin, Cisplatin (CP) treated, and CP + Melatonin treated. The cisplatin-treated group showed decreased body and ovarian weights, decreased serum E2 and AMH, increased serum LH and FSH, reduced ovarian levels of SOD, CAT, GSH, and TAC, and increased ovarian MDA. The histopathological examination of the cisplatin-treated group showed deleterious changes within ovarian tissue in the form of damaged follicles and corpus luteum, hemorrhage, and inflammatory infiltrates with faint PAS reaction in zona pellucida, increased ovarian collagen deposition, and marked expression of caspase-3 immune reaction in granulosa and theca cells, stroma, and oocytes. Alongside, there was a significant downregulation in the mRNA expression of steroidogenic enzymes, IL10, AMPK, PI3K, AKT, mTOR, and PTEN, while TGF-β1, IL1β, IL6, TNF-α, NF-Kβ, P53, p38-MAPK, JNK, and FOXO3 mRNA expressions were upregulated in cisplatin-treated rats’ ovarian tissue. Coadministration of cisplatin-treated rats with melatonin reversed these changes significantly. In conclusion, melatonin’s antioxidant, anti-inflammatory, and anti-apoptotic activities could modulate ovarian disturbances induced by cisplatin and preserve fertility.

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Section: Discussionsupporting

confidence: 58%

Melatonin Mitigates Cisplatin-Induced Ovarian Dysfunction via Altering Steroidogenesis, Inflammation, Apoptosis, Oxidative Stress, and PTEN/PI3K/Akt/mTOR/AMPK Signaling Pathway in Female Rats

et al. 2022

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“…Evidence suggests that the principal manifestation of cisplatin-induced ovarian damage is a loss of the healthy ovarian reserve and female fertility, frequently accompanied by increased atretic follicles [5]. The precise mechanisms underlying this drug's ovarian toxicity involve irreversible DNA damage, overloaded oxidative stress, and uncontrolled apoptosis activation [5][6][7]. Fertility-preservation strategies, such as ovarian tissue cryopreservation, embryo cryopreservation, stem cell transplantation, and oocyte donation, might benefit a proportion of tumor survivors.…”

Section: Introductionmentioning

confidence: 99%

Senotherapy Protects against Cisplatin-Induced Ovarian Injury by Removing Senescent Cells and Alleviating DNA Damage

Tang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ovarian damage induced by platinum-based chemotherapy seriously affects young women with cancer, manifesting as infertility, early menopause, and premature ovarian insufficiency. However, effective prevention strategies for such damage are lacking. Senescent cells may be induced by chemotherapeutic agents. We hypothesized that cisplatin can lead to senescence in ovarian cells during the therapeutic process, and senolytic drugs can protect animals against cisplatin-induced ovarian injury. Here, we demonstrated the existence of senescent cells in cisplatin-treated ovaries, identified the senescence-associated secretory phenotype, and observed significant improvement of ovarian function by treatment with metformin or dasatinib and quercetin (DQ) independently or in combination. These senotherapies improved both oocyte quality and fertility, increased the ovarian reserve, and enhanced hormone secretion in cisplatin-exposed mice. Additionally, attenuated fibrosis, reorganized subcellular structure, and mitigated DNA damage were observed in the ovaries of senotherapeutic mice. Moreover, RNA sequencing analysis revealed upregulation of the proliferation-related genes Ki, Prrx2, Sfrp4, and Megfl0; and the antioxidative gene H2-Q10 after metformin plus DQ treatment. Gene ontology analysis further revealed that combining senotherapies enhanced ovarian cell differentiation, development, and communication. In this study, we demonstrated that metformin plus DQ recovered ovarian function to a greater extent compared to metformin or DQ independently, with more follicular reserve, increased pups per litter, and reduced DNA damage. Collectively, our work indicates that senotherapies might prevent cisplatin-induced ovarian injury by removing senescent cells and reducing DNA damage, which represent a promising therapeutic avenue to prevent chemotherapy-induced ovarian damage.

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“…Roche and Roche (2020) reported that high levels of DABK in the extracellular environment of neighboring cells lead to a positive feedback cycle of injury and inflammation. The exposure of B 1 receptor to proinflammatory cytokines during SARS-CoV-2 infection (Colarusso et al 2020) has also been associated with leukocyte migration, oxidative stress, and increase in vascular permeability with important pulmonary repercussion (Colarusso et al 2020;Ayres et al 2020;Parekh et al 2020). In addition, it has been demonstrated that activation of the B 2 receptor is responsible for the release of nitric oxide (NO), prostacyclin, and may induce the hyperpolarization derived from the endothelium (Chow et al 2020).…”

Section: Bradykinin Pathway In the Pathogenesis Of Covid-19mentioning

confidence: 99%

Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives

Silva

Araújo-Júnior

Silva-Júnior

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects the respiratory tract. Bradykinin (BK) is a hypotensive substance that recently emerged as one of the mechanisms to explain COVID-19-related complications. Concerning this, in this review, we try to address the complex link between BK and pathophysiology of COVID-19, investigating the role of this peptide as a potential target for pharmacological modulation in the management of SARS-CoV-2. The pathology of COVID-19 may be more a result of the BK storm than the cytokine storm, and which BK imbalance is a relevant factor in the respiratory disorders caused by SARS-CoV-2 infection. Regarding this, an interesting point of intervention for this disease is to modulate BK signaling. Some drugs, such as icatibant, ecallantide, and noscapine, and even a human monoclonal antibody, lanadelumab, have been studied for their potential utility in COVID-19 by modulating BK signaling. The interaction of the BK pathway and the involvement of cytokines such as IL-6 and IL1 may be key to the use of blockers, even if only as adjuvants. In fact, reduction of BK, mainly DABK, is considered a relevant strategy to improve clinical conditions of COVID-19 patients. In this context, despite the current unproven clinical efficacy, drugs repurposing that block B1 or B2 receptor activation have gained prominence for the treatment of COVID-19 in the world.

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Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity

Cited by 13 publications

References 31 publications

Melatonin Mitigates Cisplatin-Induced Ovarian Dysfunction via Altering Steroidogenesis, Inflammation, Apoptosis, Oxidative Stress, and PTEN/PI3K/Akt/mTOR/AMPK Signaling Pathway in Female Rats

Melatonin Mitigates Cisplatin-Induced Ovarian Dysfunction via Altering Steroidogenesis, Inflammation, Apoptosis, Oxidative Stress, and PTEN/PI3K/Akt/mTOR/AMPK Signaling Pathway in Female Rats

Senotherapy Protects against Cisplatin-Induced Ovarian Injury by Removing Senescent Cells and Alleviating DNA Damage

Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives

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