Aim
Typical antipsychotics (TAPs) are commonly used to treat schizophrenia and bipolar disorder. However, extrapyramidal disorders, hyperprolactinemia, and reproductive dysfunctions have been observed in women during the use of TAPs. For this reason, less toxic and prolactin‐sparing atypical antipsychotic (AAP) drugs such as clozapine (CLN) have been developed. The aim of this study is to investigate the effect of taxifolin on possible ovarian and reproductive toxicity associated with CLN and haloperidol (HPL) in female Wistar albino rats.
Methods
The rats were grouped as healthy control group (HCG), CLN, HPL, taxifolin + clozapine (TCL), and taxifolin + haloperidol (THL). Drugs were administered to the groups for 28 days. At the end of that time, ovarian tissues of six rats from each group were taken for histopathological and biochemical analyses. Remaining six rats in groups were examined for evaluation of reproductive dysfunctions.
Results
Severe degeneration and vacuolization were observed in the primary, secondary, and primordial follicles of the ovarian tissues of CLN‐ and HPL‐treated groups, of which malondialdehyde (MDA) level was high and total glutathione (tGSH) level was low. In the taxifolin‐treated groups, taxifolin significantly prevented the increase of MDA level and decrease of tGSH level, and the severity of histopathological damage was found to be lower. In addition, it was found that taxifolin significantly prevented infertility and delay in pregnancy associated with CLN and HPL.
Conclusions
The results of this experiment suggest that taxifolin can be beneficial in treating oxidative ovarian damage, infertility, and reproductive dysfunctions induced by CLN and HPL.
Background. 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.
Objectives.To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats.
Materials and methods.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.Results. 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.
Conclusions.Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.
patients with gastric (Arjmandi et al., 2022), breast, head, neck and other cancers (Grem, 2000). 5-FU has still remained the cornerstone for colorectal cancer chemotherapy (Kobuchi et al., 2020). However, serious side effects and drug resistance phenomenon have limited its clinical use (Ciaffaglione et al., 2021). Serious cardiac side effects including cardiomyopathy, angina pectoris, ventricular tachycardia, heart failure, acute myocardial infarction and cardiogenic shock have been reported in patients treated with 5-FU (Zhang et al., 2018) . Nausea, diarrhea, vomiting, oral and intestinal mucositis, mouth ulcers, anorexia, neutropenia and thrombocytopenia are
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