The Effect of Quercetin on Ovary Functions in Rats with Cyclophosphamide Induced Ovary Damage

Background : Premature ovarian failure describes women under 40 who usually present with amenorrhea, hypergonadotropic hypogonadism, and infertility. Quercetin is an antioxidant flavonol. Quercetin’s oxidative, kinase and cell cycle inhibitor activities are known. Our study aimed to examine the efficacy of Quercetin on premature ovarian failure. Methods : Forty-eight regular-cycled adult female Wistar rats weighing 200 ± 40 grams, 10–12 weeks old, were used in the study. They were randomly divided into four groups with 12 animals. Four groups are Control, Cyclophosphamide, Cyclophosphamide + Quercetin (100 mg/kg) and Quercetin (100 mg/kg) groups. At the end of the experiment, the ovarian tissues were quickly removed. Follicles were counted to determine the ovarian reserve. Serum was extracted, and an Anti-Müllerian hormone analysis was performed. RT-PCR (reverse transcriptase–polymerase chain reaction) from ovarian tissue performed mRNA expression analysis of the Ddx4 gene. Results : As a result of Cyclophosphamide administration, it was determined that there was a decrease in both early-stage follicles and total follicles. This decrease was also statistically significant ( p < 0.05). Anti-Müllerian hormone levels were significantly lower in the group given Cyclophosphamide ( p < 0.01). On the histological examination, the number of early-stage and total follicles was significantly decreased in the Cyclophosphamide group compared to the control group, and those of the Cyclophosphamide + Quercetin were very close to that of the control group. Anti-Müllerian hormone (AMH) levels were also significantly lower in the Cyclophosphamide group compared to the control, but they were recovered to the level of the control group by Quercetin treatment. Conclusions : Our study may prove that Quercetin can protect ovarian function against Cyclophosphamide-induced ovarian damage.

[1]  S-F Zheng,et al.  Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide‐induced premature ovarian failure , 2021, Basic & clinical pharmacology & toxicology.

[2]  Mee-Sup Yoon,et al.  Premature Ovarian Insufficiency: Past, Present, and Future , 2021, Frontiers in Cell and Developmental Biology.

[3]  M. Mahmoudian-sani,et al.  Anti-inflammatory potential of Quercetin in COVID-19 treatment , 2021, Journal of inflammation.

[4]  C. Turkler,et al.  An experimental study on the long-term and short-term effects of PRP treatment on the endometrium and ovaries , 2020 .

[5]  Y. Kuang,et al.  Quercetin prevents primordial follicle loss via suppression of PI3K/Akt/Foxo3a pathway activation in cyclophosphamide-treated mice , 2020, Reproductive Biology and Endocrinology.

[6]  O. Chinot,et al.  Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook. , 2020, Cancer treatment reviews.

[7]  Xue-Ting Deng,et al.  Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[8]  Manar Elkady,et al.  Effects of quercetin and rosuvastatin each alone or in combination on cyclophosphamide-induced premature ovarian failure in female albino mice , 2019, Human & experimental toxicology.

[9]  Catalina Carrasco-Pozo,et al.  The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism , 2019, International journal of molecular sciences.

[10]  B. Joo,et al.  Establishment of Effective Mouse Model of Premature Ovarian Failure Considering Treatment Duration of Anticancer Drugs and Natural Recovery Time , 2018, Journal of menopausal medicine.

[11]  S. Asri-Rezaei,et al.  Comparative study of the protective effects of chicken embryo amniotic fluid, vitamin C and coenzyme Q10 on cyclophosphamide-induced oxidative stress in mice ovaries , 2018, Veterinary research forum : an international quarterly journal.

[12]  Q. Gao,et al.  Quercetin increases the antioxidant capacity of the ovary in menopausal rats and in ovarian granulosa cell culture in vitro , 2018, Journal of Ovarian Research.

[13]  W. Wallace,et al.  Ovarian function, fertility and reproductive lifespan in cancer patients , 2018, Expert review of endocrinology & metabolism.

[14]  G. D’Orazi,et al.  Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways. , 2017, The Journal of nutritional biochemistry.

[15]  Yu Xie,et al.  Cyclophosphamide enhances anti-tumor effects of a fibroblast activation protein α-based DNA vaccine in tumor-bearing mice with murine breast carcinoma , 2017, Immunopharmacology and immunotoxicology.

[16]  G. Bedoschi,et al.  Chemotherapy-induced damage to ovary: mechanisms and clinical impact. , 2016, Future oncology.

[17]  Subramani Parasuraman,et al.  Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid , 2016, Pharmacognosy reviews.

[18]  Yulong Yin,et al.  Quercetin, Inflammation and Immunity , 2016, Nutrients.

[19]  A. Keating,et al.  The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion. , 2016, Toxicology and applied pharmacology.

[20]  M. Gunay,et al.  The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study , 2015, Gynecologic and Obstetric Investigation.

[21]  A. Maurya,et al.  Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line , 2015, Molecular Biology Reports.

[22]  Liang Hu,et al.  Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency. , 2015, Human reproduction.

[23]  A. Bukovsky Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases , 2015, Reproductive Biology and Endocrinology.

[24]  O. Sytar,et al.  The application of multiplex fluorimetric sensor for the analysis of flavonoids content in the medicinal herbs family Asteraceae, Lamiaceae, Rosaceae , 2015, Biological Research.

[25]  Xuelin Huang,et al.  An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. , 2013, Biostatistics, bioinformatics and biomathematics.

[26]  H. Kanety,et al.  Cyclophosphamide Triggers Follicle Activation and “Burnout”; AS101 Prevents Follicle Loss and Preserves Fertility , 2013, Science Translational Medicine.

[27]  I. Ben-Aharon,et al.  Chemotherapy-induced ovarian failure as a prototype for acute vascular toxicity. , 2012, The oncologist.

[28]  S. Morgan,et al.  How do chemotherapeutic agents damage the ovary? , 2012, Human reproduction update.

[29]  V. Neveu,et al.  Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database , 2010, European Journal of Clinical Nutrition.

[30]  A. Shelling Premature ovarian failure. , 2010, Reproduction.

[31]  Kui Liu,et al.  Mechanisms maintaining the dormancy and survival of mammalian primordial follicles , 2010, Trends in Endocrinology & Metabolism.

[32]  Dr David Vauzour,et al.  Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. , 2009, Archives of biochemistry and biophysics.

[33]  S. Christin‐Maitre,et al.  [General mechanisms of premature ovarian failure and clinical check-up]. , 2008, Gynecologie, obstetrique & fertilite.

[34]  F. Anwar,et al.  Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. , 2008, Food chemistry.

[35]  G. Russo,et al.  The flavonoid quercetin in disease prevention and therapy: facts and fancies. , 2012, Biochemical pharmacology.