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

Abstract

Cyclophosphamide is used to treat various types of cancer. However, it can reduce ovarian function and fertility rate. The current study was done to compare the effects of N-acetylcysteine and vitamin E on cyclophosphamide-induced ovarian damage. Thirty-five rats were randomly divided into 5 groups: control (C), cyclophosphamide (CP, 200 mg/kg single dose intraperitoneally), T1 (cyclophosphamide + vitamin E at 200 mg/kg), T2 (cyclophosphamide + 200 mg/kg N-acetylcysteine), and T3 (cyclophosphamide + N-acetylcysteine and vitamin E at 200 mg/kg). The main measurements included total antioxidant capacity (TAC), glutathione peroxidase (GPx), malondialdehyde (MDA), interleukin 8 (IL-8), tumor necrosis factor-α (TNFα), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (ES). Except for the C and T3 groups, the other groups lost weight. A significantly lower concentration of MDA was observed in the T3 group. However, TAC was substantially increased compared to the other groups. The level of GPx in the S group was significantly reduced compared to all groups. Proinflammatory markers (IL-8 and TNFα) reached their lowest serum level in the T3 group, with a statistically significant difference compared to that of the S group. In addition, there were no significant differences in the means of primary, secondary, and graph and atretic follicles between the T3 and C group. On the other hand, a decrease in FSH and LH was observed while an increase in ES was seen in the T3 group compared to the S group. This study revealed that N-acetylcysteine and vitamin E coadministration could significantly decrease the side effects of cyclophosphamide, especially in ovarian tissue.

Therapeutic effects of garlic (Allium sativum) on female reproductive system: A systematic review

“…Garlic supplementation has been shown to reduce estrogen, progesterone, and luteinizing hormone (LH) levels, thereby reducing the hormonal imbalances that commonly occur in PCOS. Garlic has been found to contain compounds such as allicin , which may help regulate estrogen levels [ 73 , 77 , 78 ]. Modaresi et al reported that garlic can increase the secretion of estrogen and progesterone blood levels in women.…”

Protective Effect of Glutathione Administration on Ovarian Function in Female Rats with Cyclophosphamide-Induced Ovarian Damage

“…Cy lacks specificity in targeting the cell cycle, resulting in its toxicity to cells not actively undergoing division [27]. Cy also triggers inflammation, and the increased expression of cytokines facilitates programmed cell death by activating Yurttancikmaz/Ozcan/Tanoglu/Tok/ Timur/Cetin interferon alpha and gamma [28]. CYP2B and CYP3A activate Cy to produce 4-hydroxycyclophosphamide, which is eventually metabolized to phosphoramide mustard (PM) [29].…”

“…GSH supplementation or co-treatment with antioxidants significantly suppressed this effect [35]. Raeeszadeh et al [28] studied N-acetylcysteine, a precursor of GSH and vitamin E, on Cy-induced ovarian damage and demonstrated a synergistic protective effect. Other studies investigating the protective effects of 2-mercaptoethane sulfonate [20] and mirtazapine [36] against gonadotoxic medications have also revealed that preservation of antioxidant substances contributes to the preservation of ovarian function, like reduction of GSH depletion.…”

Fertility Predictors in Intrauterine Insemination (IUI)

“…There are studies in cryogenics indicating that broccoli extract in a certain dose could improve serum and testicular oxidative biomarkers, testicular structure and function, and sperm quality before and after cryopreservation improving reproductive performance [ 27 , 28 ]. In addition, with regard to ovarian function, this can be reduced by using cyclophosphamide, but the simultaneous administration of N-acetylcysteine and vitamin E could significantly reduce the side effects of cyclophosphamide, especially in the ovarian tissue [ 29 ].…”