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    Assessment of the effects of two different doses of methotrexate in rat ovarian tissue: A histological study
    (2024) Yalcın, Betul; Kalkan, Kubra Tugce; Koseoglu, Eda; Karaman, Enes; Yay, Arzu
    Aim: The use of methotrexate (MTH), a drug commonly prescribed to treat rheumatoid arthritis, cancer, and certain autoimmune diseases, has been linked to early ovarian failure and infertility in women when used in varying amounts and durations. In this study, the possible effects of MTH exposure at different doses on rat ovary were investigated histologically and immunohistochemically. Materials and Methods: A total of 21 female rats, Wistar albino, were utilized in the investigation. The control group (n = 7) was not subjected to any treatment. The 10 mg/kg MTH group (n = 7) and the 20 mg/kg MTH group (n = 7) were given intraperitoneal injections of 10 mg/kg and 20 mg/kg methotrexate, respectively. Five days after injection, the ovarian tissues were taken out of the anesthetized rats and subjected to routine histological tissue processing. The histological evaluation was performed with hematoxylin and eosin (H&E) and Masson’s trichrome (MT) on paraffin block sections. Additionally, immunohistochemical staining was performed to determine AMH immunoreactivity. Results: In both MTH groups, histopathological changes were observed, particularly in the 20 mg/kg group, and these included the presence of areas of edema as well as dilated or congested blood vessels. Furthermore, the 20 mg/kg MTH group exhibited increased fibrotic tissue in the ovarian medulla. The number of follicles and AMH immunoreactivity were observed to be reduced in the MTH groups, with the reduction reaching a statistically significant level in the 20 mg/kg MTH group ovary. In terms of AMH immunoreactivity, it is demonstrated that there is no statistical significance between the control and 10 mg/kg MTH groups. Conclusion: The dose of MTH should be considered carefully, as increasing the dose may lead to deterioration of ovarian histopathology and a reduction in the reserve of the ovary
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    Effect of N-acetylcysteine on cisplatin induced apoptosis in rat kidney
    (Cukurova Univ, Fac Medicine, 2022) Gunturk, Inayet; Seydel, G. Seyda; Dagli, Fatma; Yay, Arzu; Yazici, Cevat; Kose, Kader
    Purpose: Cisplatin is one of the most potent and widely used chemotherapeutic agents for the treatment of a wide variety of solid organ cancers. However, due to various side-effects such as nephrotoxicity, its therapeutic applications are limited. In the current study, it was aimed to investigate the effects of N-acetylcysteine (NAC), which is an effective antioxidant and anti-inflammatory agent, on cisplatin-induced apoptosis in rat kidneys. Materials and Methods: Twentyfour male Wistar rats were separated into 4 equal groups: Control, NAC-250, cisplatin (CP), and CP+NAC groups. Rats in the experimental groups were treated with intraperitoneally (i.p.) single-dose cisplatin (10 mg/kg) and NAC (i.p., 250 mg/kg) for 3 days. Results: At the end of the experiment, nephrotoxicity was confirmed by blood urea nitrogen and creatinine levels, and the apoptotic changes were demonstrated by TdT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and caspase-3 levels in rat kidneys. The number of TUNEL-positive cells and caspase-3 levels were significantly increased by cisplatin. Treating the rats with NAC significantly decreased TUNEL-positive cells and caspase-3 levels. Conclusion: These data suggest that apoptotic cell death is involved in the pathogenesis of cisplatin-induced nephrotoxicity, and that the inhibition of apoptosis plays a central role in the beneficial effects of NAC.
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    The effect of ionizing radiation on the fetal bone development in pregnant rats: Role of melatonin
    (Wiley, 2024) Tokpinar, Adem; Nisari, Mehtap; Yilmaz, Seher; Yay, Arzu; Yildiz, Oguz Galip; Balcioglu, Esra; Alisan, Pinar
    Radiation has been widely used in many business sectors over the last century. Our study investigated the possible teratogenic effects of radiation on the bones of rat fetuses and the protective effect of melatonin against these effects. In this study, 15 pregnant female Wistar albino rats were used. These rats were divided into four groups: the control group, melatonin group (10 mg/kg/day), radiation group (0.5 gray), radiation (0.5 gray) + melatonin group (10 mg/kg/day), and sham group (1 mm hanks/day). The skeletal system development of fetuses was examined with double skeletal and scanning electron microscope (SEM), histopathological methods. In our study, fetal weight, placental weight, and fetal morphometric values were found to be statistically significantly decreased in the radiation group compared to the control group (p < .05). In immunohistochemistry (IHC) analysis, alkaline phosphatase, and tartrate-resistant acid phosphatase) concentrations were found to be significantly lower in the radiation group compared to the other groups. In the SEM analysis, it was observed that the amount of calcium and sodium decreased when the radiation group was compared with the other groups. As a result, when exposed to ionizing radiation during pregnancy, melatonin has a protective feature against the negative effects of radiation on the bone development of fetuses.
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    The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model
    (Tubitak Scientific & Technological Research Council Turkey, 2019) Gunturk, Inayet; Yazici, Cevat; Kose, Kader; Dagli, Fatma; Yucel, Bilal; Yay, Arzu
    Background/Aim: Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Materials and methods: Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental groups were treated intraperitoneally (i.p.) with a single dose of cisplatin (10 mg/kg body weight) and i.p. with NAC (250 mg/kg body weight) for three consecutive days. Nephrotoxicity was determined by plasma BUN and creatinine levels. In tissue samples, myeloperoxidase (MPO), nuclear factor-kappa B (NF-kB), high mobility group box-1 (HMG B-1), total oxidant status (TOS), and total antioxidant status (TAS) levels were measured. Kidneys were analyzed histopathologically as well. Results: It was revealed that cisplatin was not effective on MPO, HMGB-1 and NF-kB levels but did increase TOS levels and decrease TAS levels in tissue samples. Interestingly, NAC elevated MPO and HMGB-1 levels significantly. Nevertheless, NAC ameliorated histological and functional changes in kidney tissues. Conclusion: It is suggested that inflammation has a limited effect on cisplatin nephrotoxicity in this experimental design, and, as reflected by decreased BUN and creatinine levels, NAC can be used as an additional therapeutic agent in standard cisplatin treatment protocols.