Protective Effect of Adenosine Triphosphate against 5-Fluorouracil-Induced Oxidative Ovarian Damage in vivo.

OBJECTIVE: The aim of our study was to analyze the effect of ATP on possible ovarian damage of 5-FU in rats. METHODS: The animals were divided to three groups; healthy group (HG), 5-FU alone group (FUG) and ATP+5-FU administered group (AFU). The ATP 4 mg/kg was injected intraperitoneally (IP) into the AFU group. The same volume of saline (0.9% NaCl) as the solvent was administered intraperitoneally to the HG and FUG groups. One hour after administering ATP and solvent, 5-FU 100 mg/kg was injected intraperitoneally to the animals in the AFU and FUG groups. ATP was administered to the animals once a day for 10 days. On the 1st, 3rd and 5th days of 5-FU, one dose (total of 3 doses) was administered. On day 10, the animals were euthanasia with high-dose anaesthesia and ovarian tissues were removed. The removed ovaries were analyzed biochemically andhistopathological. RESULT: ATP significantly suppressed both the increase in MDA and IL-6 levels, and the decrease in tGSH, SOD and CAT levels. Treatment with ATP significantly suppressed the severe vacuolization and primordial follicle degeneration induced by 5-FU in our study. CONCLUSION: ATP was possible to be useful for the treatment of 5-FU-induced ovarian damage.

Effect of thiamine pyrophosphate on cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats.

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. MATERIAL 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-1ß). 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.

The effect of taxifolin on oxidative ovarian damage and reproductive dysfunctions induced by antipsychotic drugs in female rats.

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.

The effect of adenosine triphosphate on bevacizumab-induced ovarian damage and reproductive dysfunction in rats.

We investigated the effect of ATP's protection against possible bevacizumab-induced ovarian damage and reproductive dysfunction in female albino Wistar rats. A total of 42 rats, 36 females, and 6 males were used in the experiment. Normal saline (0.9% NaCl) was injected as a solvent to the Bevacizumab (BVZ; n = 12) and Control (n = 6) groups. 25 mg/kg ATP was injected intraperitoneally (i.p.) to the ATP + bevacizumab (ABZ; n = 12) group. One hour after ATP and solvent administration, 10 mg/kg bevacizumab was i.p. injected to the ABZ and BVZ groups. Bevacizumab was administered once a day every two weeks; ATP was administered one a day for 30 days. At the end of this period, six rats from each group were sacrificed with high dose of anesthesia (thiopental sodium 50 mg/kg) and biochemical and histopathological examinations were performed in ovarian tissues. Mature male rats were kept in the laboratory for two months to breed the remaining female animals. The values showed that the oxidant parameters increased in the ovarian tissue of the BVZ group compared to the healthy controls and the ABZ group, while antioxidant parameters decreased. The number of breeding animals was significantly decreased in the BVZ group compared to the Control and the ABZ groups. This result suggests that ATP may be effective in preventing oxidative damage to the ovaries and infertility induced by bevacizumab.