Abstract
Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. Thiamine pyrophosphate (TPP) to be investigated for its effect on cyclophosphamide-induced ovarian damage and reproductive dysfunction in the present study is the active metabolite of thiamine. It has been shown that TPP protects organs and tissues from oxidative stress and proinflammatory cytokine damage. To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats. Albino Wistar type female rats were divided into healthy control (HG), cyclophosphamide (CYC) and TPP + cyclophosphamide (TPPC) groups (for each group, n = 12). Thiamine pyrophosphate at a dose of 25 mg/kg was injected intraperitoneally (ip.) in the TPPC group, and 0.9% NaCI solution was injected ip. in the CYC and HG groups. One hour after the injection, 75 mg/kg of cyclophosphamide was administered ip. in the TPPC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, 6 rats from each group were euthanized with a high dose of anesthetic (50 mg/kg of sodium thiopental). Biochemical and histopathological examinations were performed on the extracted ovarian tissue. The remaining animals were kept in the laboratory with mature male rats for 2 months for reproduction. Thiamine pyrophosphate significantly decreased the cyclophosphamide-induced increase in the levels of the oxidant parameter malondialdehyde (MDA), proinflammatory nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β). In addition, TPP decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility. Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.
Highlights
Cyclophosphamide is a drug used in various types of cancer
thiamine pyrophosphate (TPP) decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility
Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility
Summary
Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. The common adverse reactions reported in clinical studies include hemorrhagic cystitis, amenorrhea, myelosuppression, alopecia, nausea, and vomiting.[5,6] Renal tubular necrosis, pulmonary fibrosis, cardiotoxicity, and infertility have been shown among other toxic effects associated with cyclophosphamide.[7] It is stated that cyclophosphamideinduced infertility is caused by ovarian failure.[8] Infertility due to ovarian failure is the most common and serious side effect of cyclophosphamide and occurs in 30–70% of women receiving the treatment.[9,10] It has been reported that cyclophosphamide causes ovarian failure through oxidative and inflammatory damage.[11] Nair et al showed that cyclophosphamide-induced damage in the ovarian tissue was caused by a decrease in the endogenous antioxidant glutathione (GSH) and an increase in proinflammatory tumor necrosis factor alpha (TNF-α).[12] In a study by Khedr, it was emphasized that cyclophosphamide-induced infertility was associated with an increase in malondialdehyde (MDA) – a lipid peroxidation (LPO) product in the ovarian tissue.[13] The information obtained from the literature suggests that antioxidant and anti-inflammatory drugs can be beneficial in the prevention or treatment of cyclophosphamide-induced infertility
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