Can ebselen prevent cisplatin-induced ovarian damage?

Soyman, Zeynep; Uzun, Hafize; Bayındır, Nihan; Eşrefoğlu, Mukaddes; Boran, Birtan

doi:10.1007/s00404-018-4750-4

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…A recent report indicated that cisplatin therapy leads to the dilatation, vacuolization, and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues, as seen in our study (Eren et al, 2018). The previous findings and our results also confirmed that cisplatin produces high H score in the kidney (Ozkok and Edelstein, 2014;Eren et al, 2018;Soyman et al, 2018;). In the literature, these histopathological findings point out the nephrotoxicity (Yao et al, 2007).…”

Section: Discussionsupporting

confidence: 90%

“…The underlying mechanisms of tubular cell death due to cisplatin treatment includes oxidative stress, DNA adducts, inflammation, mitochondrial dysfunction, apoptosis, and direct cytotoxicity (Yao et al, 2007). However, several studies showed the protective effects of antioxidative molecules against cisplatin-induced damages (Eren et al, 2018;Haghi-Aminjan et al, 2018;Soyman et al, 2018). Therefore, we may suggest that squalene treatment ameliorated the cisplatin-induced histopathological damages in the kidney tissue by regulating the balance of the redox system due to its antioxidative effect (Ondrejková et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice

Sakul¹,

Ozansoy²,

Elibol³

et al. 2019

Turk J Biol

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The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-γ) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney through activation of AKT/mTOR signaling pathway by regulating the balance of the redox system due to its antioxidative effect.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice

Sakul¹,

Ozansoy²,

Elibol³

et al. 2019

Turk J Biol

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“…They investigated ovarian injury by examining follicles histochemically and evaluated the immunoreactive intensity of AMH in ovarian tissue 16 . Soyman et al reported that antioxidant ebselen prevents cisplatin‐induced ovarian damage 39 . They found high Cu/Zn‐SOD and GSH levels, low malonyldialdehyde (MDA) and NOx levels, and high‐serum AMH hormone levels in the ovarian tissue of ebselen treated mice.…”

Section: Discussionmentioning

confidence: 99%

The effects of recombinant klotho in cisplatin‐induced ovarian failure in mice

Bıyık¹,

Özatik²,

Albayrak

et al. 2021

J of Obstet and Gynaecol

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Aim To investigate whether recombinant klotho given concomitantly with cisplatin is effective in preventing cisplatin‐induced ovarian damage. Methods Thirty‐two adult female mice were divided into four groups. Saline was given to the first group, cisplatin to the second group, recombinant mouse klotho to the third group, and recombinant mouse klotho + cisplatin to the fourth group. The removed ovarian tissues were examined and groups were compared histologically and immunohistochemical examination for antimullerian hormone (AMH), superoxide dismutase (SOD) and catalase expression were done. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were measured by ELISA. Results Ovarian tissue weight, primary and secondary follicle counts were higher in cisplatin + recombinant klotho group compared to cisplatin group in our study (respectively p < 0.0001, p < 0.0001, and p = 0.010). Injury scores (stromal congestion, edema and infiltration, follicular degeneration scores and edema in corpus luteum scores) were similar between cisplatin and cisplatin + recombinant klotho groups (all p > 0.05). AMH staining intensities were similar between cisplatin and cisplatin + recombinant klotho groups (p = 0.925). There was no difference between the groups in terms of SOD, GPx, and GR (p > 0.05). Conclusions The recombinant klotho administered before cisplatin could partially protect the ovarian tissue from cisplatin‐induced ovarian damage considering that there was no difference in histologic injury score parameters, AMH staining intensity and oxidative stress markers between cisplatin and cisplatin plus klotho groups except that klotho preserved follicules to some extent. The antioxidant mechanism of action of klotho may not be the primary protection mechanism in cisplatin induced ovarian injury.

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“…Additionally, ebselen ameliorates ovarian damage by reducing oxidative stress caused by cisplatin (Ref. 37). The administration of ebselen can induce apoptosis in multiple myeloma (MM) cell lines by enhancing the production of endogenous ROS (Ref.…”

Section: Involvement In Diseasementioning

confidence: 99%

“…Based on extensive research, several potential clinical applications of ebselen in the treatment of different diseases have been reported in cell lines studies (Refs 20, 21, 27, 33), animal experiments (Refs 28, 34, 35, 36, 37) and clinical trials (Refs 38, 39, 40, 41). In mammalian cells, ebselen works as a GPx-like compound and peroxiredoxin mimic through Trx and TrxR to scavenge hydrogen peroxide and peroxynitrite (Ref.…”

Section: Introductionmentioning

confidence: 99%

Ebselen, a multi-target compound: its effects on biological processes and diseases

Cai

Xiang

et al. 2021

Expert Rev. Mol. Med.

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Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.

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Can ebselen prevent cisplatin-induced ovarian damage?

Abstract: Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

Cited by 13 publications

References 31 publications

Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice

Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice

The effects of recombinant klotho in cisplatin‐induced ovarian failure in mice

Ebselen, a multi-target compound: its effects on biological processes and diseases

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