Diosmin Mitigates Cyclophosphamide Induced Premature Ovarian Insufficiency in Rat Model

Abstract

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.

Comparison of Animal Models for Premature Ovarian Insufficiency Induced by Different Doses of Cyclophosphamide: a Network Meta‑analysis

“…After carefully reviewing the full-text review ,13 studies were excluded due to the discrepancy of inclusion and exclusion criteria mentioned above. 14 studies [9][10][11][12][13][14][15][16][17][18][19][20][21][22] were nally selected for meta-analysis. A PRISMA ow diagram describing the process of literature search and selection is presented in Fig.…”

Impact of Co-Administration of N-Acetylcysteine and Vitamin E on Cyclophosphamide-Induced Ovarian Toxicity in Female Rats

“…Cycled female Wistar rats were randomly divided into five groups of 7 as follows: Group (C): rats were given only distilled water and chow Group (S): rats were given cyclophosphamide single i.p. injections of CP (200 mg/kg of body weight) [ 16 ] Group (T1): rats received cyclophosphamide and vitamin E at a dose of 200 mg/kg daily gavage Group (T2): rats received cyclophosphamide and n-acetylcysteine at a dose of 200 mg/kg daily gavage Group (T3): rats received cyclophosphamide with n-acetylcysteine and vitamin E [ 17 ] …”

“…Group (S): rats were given cyclophosphamide single i.p. injections of CP (200 mg/kg of body weight) [ 16 ]…”

Hyperin Alleviates Triptolide-Induced Ovarian Granulosa Cell Injury by Regulating AKT/TSC1/mTORC1 Signaling

“…In recent years, medicinal plants are widely studied [ 6 – 8 ], some of which have anticancer activity [ 9 ], natural anthraquinone derivatives have immunomodulatory, antibacterial, and anti-inflammatory properties [ 10 ], and many studies have proved that flavonoids can act as antioxidants to prevent the degradation of antioxidants and age-related cellular components [ 11 ]. Traditional Chinese medicine has been employed for treating POI and has achieved excellent efficacy [ 12 ].…”

“…Clinical symptoms of POI primarily occur in response to dysregulated folliculogenesis and estrogen deficiency, including vulvovaginal atrophy, oligomenorrhea, amenorrhea, infertility, and vasomotor instability [ 10 , 17 ]. Abnormal follicular atresia, a process characterized by follicular degeneration during growth and development, might enhance follicular depletion and result in ovarian insufficiency [ 10 ]. The decrease of ovarian reserve is related to the decrease of the number or quality of follicles and oocytes [ 18 ].…”