Omer Erkan Yapca

The Effect of Mirtazapine on Cisplatin-Induced Oxidative Damage and Infertility in Rat Ovaries

Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After this period, six rats from each group were randomly selected, and malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), total gluthatione (tGSH), gluthatione peroxidase (GPx), superoxide dismutase (SOD), and 8-hydroxy-2 deoxyguanine (8-OH Gua) levels were measured in their ovarian tissues. Reproductive functions of the remaining rats were examined for 6 months. The MDA, MPO, NO groups and 8-OH Gua levels were higher in the cisplatin-treated groups than the controls, which was not observed in the mirtazapine and cisplatin groups. GSH, GPx, and SOD levels were reduced by cisplatin, which was prevented by mirtazapine. Cisplatin caused infertility by 70%. The infertility rates were, respectively, 40% and 10% for the 15 and 30 mg/kg mirtazapine administered groups. In conclusion, oxidative stress induced by cisplatin in the rat ovary tissue causes infertility in the female rats. Mirtazapine reverses this in a dose-dependent manner.

Benefits of the antioxidant and anti‐inflammatory activity of etoricoxib in the prevention of ovarian ischemia/reperfusion injury induced experimentally in rats

This study is a biochemical investigation of the effect of etoricoxib, a selective cyclooxygenase (COX)‐2 inhibitor, on ischemia/reperfusion (I/R) injury experimentally induced in rat ovaries.

Ischemia-Reperfusion Damage

Ischemia-reperfusion damage is a complex pathological process that begins with tissue anoxia and continues with the production of free oxygen radicals, expanding with the inflammatory response. The literature suggests the importance of antioxidant and anti-inflammatory treatment to treat ischemia-reperfusion-related tissue damage.

Use of thiamine pyrophosphate to prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary

OBJECTIVE To investigate whether thiamine pyrophosphate can prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary. Biochemical examinations of the ovaries were also performed. STUDY DESIGN Rats were divided into two main groups of three subgroups each. An ischemia reperfusion model was established in the first main group, while surgical unilateral ovariectomy was performed in the second. Thiamine pyrophosphate and melatonin were administered to the subgroups. No additional procedure was performed in the control groups. The rats were then left in laboratory environments and their fertility levels were determined. Malondialdehyde, total glutathione and DNA damage products were measured in those rats from which ovarian tissue was collected. RESULTS The results showed that thiamine pyrophosphate prevented ischemia/reperfusion injury-related infertility, but melatonin did not provide adequate prevention. However, reproduction in healthy animals receiving melatonin began earlier compared to those receiving thiamine pyrophosphate. Melatonin suppressed oxidative stress caused by ischemia/reperfusion in ovarian tissue significantly better than did thiamine pyrophosphate. CONCLUSIONS We think that different mechanisms, in addition to antioxidant activity, are involved in the prevention of reperfusion-associated infertility after ischemia.

Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies

Abstract Objective: Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. Methods: We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Results: Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. Conclusions: These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

Controlled reperfusion for different durations in the treatment of ischemia–reperfusion injury of the rat ovary: evaluation of biochemical features, molecular gene expression, and histopathology

High numbers of proinflammatory cells (PMNLs), which are carried by the blood to ischemic tissue during reperfusion, are considered responsible for inducing the inflammatory response that occurs in ischemia-reperfusion (I/R) injury. Our objective was to determine the controlled reperfusion (CR) interval duration (CRID) that would minimize the injury caused by the PMNLs that infiltrate ischemic tissue. Animal groups were divided into the following groups: Sham group, ovarian I/R group (OIR), and ovarian ischemia controlled-reperfusion groups OICR-1, OICR-2, OICR-3, OICR-4, OICR-5, OICR-6, which had their ovarian artery opened and then closed for 10, 8, 6, 4, 2, or 1 s, respectively. The results show that the COX-2 activity and the gene expression decreased while the COX-1 activity and the gene expression were found to be increased in parallel to the shortening of the period in CRID. From the histopathological examinations, the findings of hemorrhage, edema, congested vascular structures, degenerated cells, and migration and adhesion of PMNLs were scaled as follows: Sham group < OICR-6 < OICR-5 < OICR-4 < OICR-3 < OICR-2 < OICR-1. The results from the histopathological assessments were consistent with the molecular and biochemical findings. In conclusion, our findings suggest that increased COX-2 activity plays a role in I/R injury of the rat ovary, and that controlled reperfusion for 3, 2, or 1 s following 2 h of ischemia may attenuate the effects of I/R injury.

The effect of rutin on ovarian ischemia-reperfusion injury in a rat model

Abstract The effect of rutin on ovarian ischemia-reperfusion (I/R) injury was investigated in this experimental study. Eighteen Wistar albino female rats were divided into three groups as follows: I/R group (IRG; n = 6), 50 mg/kg rutin + I/R group (RG; n = 6), and a healthy control group scheduled for a sham operation (SG; n = 6). 2 h of ischemia and following 2 h of reperfusion were created in the IRG and RG by using a torsion model involving atraumatic vascular clips. Rutin, a flavonoid glycoside, was injected intraperitoneally at the dose of 50 mg/kg to RG group 1 h before reperfusion. Then, rats were euthanized and their ovaries were removed for biochemical and histopathological examination and also assessment of the gene expressions. IRG group had a significant increase in malondialdehyde (MDA) levels, in the expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), and also in the activity of cyclooxygenase 2 (COX-2) unlike the significant decrease in total glutathione (tGSH) levels and the activity of COX-1 when compared to the SG group. However, rutin significantly decreased MDA levels, the expressions of TNF-α and IL-1β, and also the activity of COX-2 while it increased significantly tGSH levels and the activity of COX-1 in the RG group in comparison with the IRG group. Rutin ameliorated the I/R-induced ovarian injury in rats via its possible antioxidative and anti-inflammatory effects.

Vaginal Misoprostol Compared With Buccal Misoprostol for Termination of Second-Trimester Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of vaginal misoprostol with buccal misoprostol for second-trimester termination of pregnancies. METHODS: In a randomized trial, we compared 400 micrograms vaginal and buccal misoprostol every 3 hours for up to six doses for induction of labor at 13–24 weeks of gestation with a live fetus and intact membranes. Women who had a uterine scar were excluded from the study. The primary outcome of the study was induction-to-abortion interval. Based on a two-tailed &agr; of 0.05, we planned to include 65 patients per group to detect a 50% difference in the primary outcome with a power of 80%. RESULTS: From January 2014 to December 2014, 172 women were screened and 130 were randomized: 65 vaginal and 65 buccal misoprostol. Characteristics of patients were similar between groups. Patients administered vaginal misoprostol compared with buccal misoprostol had a shorter induction-to-abortion interval (25±17 hours compared with 40±29 hours, P=.001) and a higher abortion rate within both 24 hours (41 [63%] compared with 27 [42%] P=.014) and 48 hours (59 [91%] compared with 44 [68%], P=.001). Complete abortion rates were similar in both groups (vaginal 51 [78%] compared with buccal 54 [83%]). The incidence of side effects was similar for both groups. The perceived pain was higher in the buccal group, but the small difference did not appear to be clinically meaningful. CONCLUSION: Vaginal compared with buccal misoprostol administration has a shorter induction-to-abortion interval for second-trimester termination of viable pregnancies. However, both administration routes are equally effective for induction of termination. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT02048098. LEVEL OF EVIDENCE: I

Congenital Ewing’s Sarcoma, a Rare and Difficult Diagnosis: a Case Report

We have interestedly read the article written by Thalia Wong BS in July 2015, which is about Pediatric Blood Cancer, including clinical findings and results of infants <1 year of age with Ewing sarcoma. We report a case with congenital Ewings sarcoma that easily interfered with rabdomyosarcoma in a pregnant woman. A 32-year-old multigravida with a big neck mass at 35 weeks was referred to our clinic. The final diagnosis of extraskeletal Ewings sarcoma was made. Hepatic metastasis was detected and treatment by chemotherapy was initiated. Ewings sarcoma is usually noted among adolescents or young adults and more rarely than among newborns. This case is important because of its rarity.

Low transcriptional activity of PON2 in recurrent abortion: A novel therapeutic agent?

OBJECTIVE Oxidative stress has been reported to be associated with various pregnancy complications and to play key roles in many of them. An inadequate level of antioxidant defense may eventually lead to an early pregnancy loss. There is a lack of information about the roles of the PON2 and PON3 enzymes in the etiology of the cases of unexplained recurrent abortus. The aim of our study is to determine and present the data regarding the roles of these enzymes for the first time. MATERIALS AND METHODS We measured the transcriptional levels of the PON2 and PON3 enzymes in the curettage materials obtained from the patients with unexplained recurrent abortus (n=25) and compared the results with those measured in the abortus materials from healthy pregnant women (n=50) who had undergone a voluntary abortion. The transcriptional activities of PON2 and PON3 enzymes were measured through quantification of their respective mRNAs by RT-qPCR assay. For each gene, 2-ΔCt replication values of the control and the patient groups were compared using the Students t-test, and the p values were calculated thereafter. Fold-changes in the enzyme transcription levels were interpreted as up- or down-regulation. RESULTS PON2 mRNA expressions were found to be highly decreased in the patient group (p=0.000002). PON3 transcription, when compared to the healthy pregnant women, was found to be down-regulated in the patient group; however, the difference was not statistically significant (p=0.69). CONCLUSIONS In this study, we evaluated the expressional regulation of the PON2 and PON3 enzymes in unexplained recurrent abortus. Our results demonstrate for the first time that the expressions of PON2 and PON3 are down-regulated in the abortion specimens of the patients with recurrent miscarriage. Although both enzymes had low expression levels, the decrease in the transcriptional activity of PON2 revealed a high statistical significance. According to these results, it is rational to speculate that PON2 may be a novel therapeutic agent in the management of the cases with unexplained recurrent abortion.