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    A histological examination of the effects of Ferula elaeochytris extract on kidney and liver tissues in myoglobinuric acute renal failure
    (Taylor & Francis Ltd, 2024) Yildiz, Fatma; Gungor, Meltem; Sezginer, Perihan; Aksak, Tiince
    Myoglobinuric acute renal failure (MARF) is a structural and functional disorder that occurs in the kidney following the release of muscle cell contents into the circulation. In this present study, possible protective and curative effects of Ferula elaeochytris extract against kidney and liver damage in experimentally induced MARF in a rat model were investigated. 3-4 Month-old, 200-250 g Sprague Dawley rats were divided into 8 equal groups with 7 rats per group. Group I was a no-intervention Control group. All groups except for the Group I were dehydrated for 16 hours. Following this dehydration, 50% v/v aqueous glycerol solution was injected into both hind leg muscles of the animals, at a dose of 8 ml/kg. The rats were given physiological saline (SF) once orally before the model was administered (Group II) and after the model was administered (Group V). Similarly, two different doses of Ferula elaeochytris root extract (40 mg/kg and 80 mg/kg) were dissolved in 2 ml of SF and administered orally before (Groups III and IV) and after (Group VI, VII) the model was created. Following the experimental period, kidney and liver tissues were removed from all groups, and fixed in 10% neutral formaldehyde solution for light microscopic examinations. Intracellular vacuolization, enlargement in the Bowman's space, widespread atrophy in the tubular structures, luminal enlargement, and desquamation were detected in the kidney tissue sections of all the experimental model groups. In the liver tissue sections, was detected hepatocyte degeneration, intracellular vacuolization, irregularity in cell membrane borders, and apoptotic bodies. These histopathological consequences of MARF were evaluated for all groups, and whereas a curative effect of Ferula elaeochytris could be seen, its protective effect was higher than its curative effect.
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    Performance of oral Bosentan-loaded SNEDDS and S-SNEDDS tablets: Biodistribution in mice, echocardiography and histology studies in pulmonary arterial hypertension rat model
    (Elsevier, 2025) Usta, Duygu Yilmaz; Olgac, Seval; Demirel, Murside Ayse; Kula, Serdar; Elmas, Cigdem; Sezginer, Perihan; Kavgaci, Akif
    Bosentan monohydrate (BOS) is the most preferred molecule for treating the rare pulmonary arterial hypertension (PAH) disease. BOS shows low solubility and high variability when administered orally. This study evaluated the pharmacodynamic biodistribution, echocardiography, and histology results of BOS-loaded SNEDDS and BOS-loaded S-SNEDDS tablets. Pharmacodynamic biodistribution studies were conducted with male Balb/c mice (8 weeks old, 18-20 g) after oral administration. XenoLight (TM) DiR and VivoTag (R) 680XL fluorescent dyes were used to monitor biological distribution and absorption with the In Vivo Imaging System (R) (IVIS (R)). Pharmacodynamic echocardiography and histology studies were carried out with Wistar rats (8-10 weeks old, 250-300 g). The PAH rat model was successfully induced with monocrotaline (MCT), which is one dose (60 mg/kg) was intraperitoneally injected. The reference drug (Tracleer (R) 125 mg tablet) and BOS-loaded SNEDDS and S-SNEDDS tablets were administered as 50 mg/kg; 2 mL per os to the treatment groups. Pharmacodynamic biodistribution studies showed that real-time biodistribution in the body, ex-vivo region of interest (ROI) values of organs, and total fluorescence emission were increased (p < 0.05). It has been confirmed that the formulations enter the systemic circulation via the lymphatic system, do not have a first-pass effect in the liver, and show no emission in the liver. The echocardiographic study was performed for up to 14 days and no difference was found between the treatment groups which are the reference tablet (Tracleer (R)), BOS-loaded SNEDDS, and BOS-loaded S-SNEDDS tablet (p > 0.05). Hematoxylin and Eosin (H&E) and Immunohistochemical (IHC) staining were done for the histology studies. These studies showed that the BOS-loaded formulations have a similar therapeutic effect on histopathological phenomena in lung and liver tissues. As the histological evaluation results, lower-dose formulations were found to be more effective than the same dose reference tablet in terms of improvements in histological parameters (p < 0.05). Comprehensive and comparative in vitro and in vivo studies indicate that BOS-loaded formulations could be an alternative oral drug delivery system for PAH treatment compared to the reference product.
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    The effect of controlled ovarian hyperstimulation on ovarian reserve via PTEN pathway
    (Bioscientifica Ltd, 2022) Sezginer, Perihan; Elmas, Cigdem; Yildiz, Fatma
    This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare's serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries. Lay summary Today, approximately 10-15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman's body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman's menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.