Protective Effects of Antioxidants on Cyclophosphamide-Induced Ovarian Toxicity

Barberino, Ricássio de Sousa; Silva, Regina Lucia S.; Palheta, Raimundo C.; Smitz, Johan E.J.; Matos, Maria Helena Tavares de

doi:10.1089/bio.2021.0159

Cited by 13 publications

(3 citation statements)

References 188 publications

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“…In vitro and animal model studies have shown that cyclophosphamide can induce apoptosis in granular layer cells and, in addition, cause inflammation and damage to the blood vessel system, decrease the production of antioxidant enzymes, and induce mitochondrial dysfunction [ 7 , 9 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ]. On the other hand, the role of apoptosis in PMFs is ambiguous.…”

Section: Gynotoxic Properties Of Anticancer Drugsmentioning

confidence: 99%

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

Markowska,

Antoszczak,

Markowska

et al. 2024

Cancers

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Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs.

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Section: Gynotoxic Properties Of Anticancer Drugsmentioning

confidence: 99%

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

Markowska,

Antoszczak,

Markowska

et al. 2024

Cancers

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“…While a fraction of these studies reported no changes in response rate or noted that toxicity-related studies were not pertinent to the report, most of the studies found the use of antioxidants alongside chemotherapy to be beneficial. In a review on antioxidant and cytoprotective compounds shown to protect against cyclophosphamide-induced ovarian damage in murine models, the nutrient and metabolic antioxidants included quercetin, resveratrol, capsaicin, curcumin, diosmin, hesperidin, α-tocopherol, tocotrienols, syringic acid, crocetin, and melatonin [82]. Many of these compounds have been highlighted in additional reviews on antioxidants as natural adjuvants in cancer treatment [9,83,84].…”

Section: Section 2: Potential Of Antioxidants To Protect Against Chem...mentioning

confidence: 99%

Chemotherapy induced oxidative stress in the ovary: drug-dependent mechanisms and potential interventions

Trujillo

Odle

Aykin-Burns

et al. 2022

Biology of Reproduction

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Cancer incidence and relative survival are expected to increase over the next few decades. With the majority of patients receiving combinatorial chemotherapy, an increasing proportion of patients experience long-term side effects from treatment— including reproductive disorders and infertility. A limited number of studies have examined mechanisms of single-agent chemotherapy-induced gonadotoxicity, with chemotherapy-induced oxidative stress being implicated in the loss of reproductive functions. Current methods of female fertility preservation are costly, invasive, only moderately successful, and seldom presented to cancer patients. The potential of antioxidants to alleviate chemotherapy has been overlooked at a time when it is becoming increasingly important to develop strategies to protect reproductive functions during chemotherapy. This review will summarize the importance of reactive oxygen species homeostasis in reproduction, chemotherapy-induced mitochondrial dysfunction in oocytes, chemotherapy-induced oxidative stress, and several promising natural adjuvants.

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“…Cyclophosphamide (CP) is an anticancer drug widely used in the treatment of various cancers including breast cancer (Kimura et al 2021), prostate cancer (Li et al 2022) and ovarian cancer (Handolias et al 2016), but its chronic use can cause severe damages to normal living cells (El-Emam 2021, Barberino et al 2023). After administration, CP is transformed into its active metabolites phosphoramide mustard (responsible for its antineoplastic potential) and acrolein (toxic metabolite of CP) with the action of cytochrome P450 mixed functional oxidase system (Zhang et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of silver nanoparticles using Pterorhachis zenkeri: Characterization and evaluation of antioxidant, anti-apoptotic, and androgenic properties in TM3 Leydig cells exposed to cyclophosphamide

Deeh,

Natesh,

Alagarsamy

et al. 2024

Preprint

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We fabricated silver nanoparticles (AgNPs) using Pterorhachis zenkeri, characterized by Atomic Force Microscopy (AFM) and determined their antioxidant potentials in vitro. Results confirmed the fabrication of AgNPs by using P. zenkeri as a bioreducing agent for the first time. AgNPs possessed potent antioxidant activity in vitro. Furthermore, the TM3 cells were treated for 24 h with AgNPs, vitamin E and cyclophosphamide (CP) at different concentrations (25, 50, 100, 250 and 500 µg/ml). The cells morphology, apoptosis, mitochondrial membrane depolarisation (MMD), Reactive Oxygen Species (ROS), caspase 3/9, oxidative stress-related enzymes, testosterone, and the mRNAexpression of steroidogenic acute regulatory protein (StAR) were measured. Results revealed that AgNPs, vitamin E and CP decreased the cell viability in a dose-dependent manner, but did not affect the TM3 cells morphology after treatment. The cytotoxicity of CP in TM3 cells was alleviated after AgNPs application. For instance, AgNPs significantly (p<0.001-0.05) reduced the MMD, ROS production, and caspase 3/9 activities, but increased the activities of superoxide dismutase, catalase and glutathione peroxidase in the TM3 cells. Moreover, AgNPs improved testosterone production by activating StAR machineries. These results indicate that AgNPs/P. zenkeri could be a potential alternative drug in the management of oxidative stress and androgen deficit associated with CP chemotherapy.

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Protective Effects of Antioxidants on Cyclophosphamide-Induced Ovarian Toxicity

Cited by 13 publications

References 188 publications

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

Chemotherapy induced oxidative stress in the ovary: drug-dependent mechanisms and potential interventions

Biosynthesis of silver nanoparticles using Pterorhachis zenkeri: Characterization and evaluation of antioxidant, anti-apoptotic, and androgenic properties in TM3 Leydig cells exposed to cyclophosphamide

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