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    ACUTE AND LONG-TERM PATHOLOGICAL EFFECTS OF COVID-19 ON THE PLACENTA DURING SECOND TRIMESTER AND LABOR
    (Univ Quindio, 2023) Tast, Fatih; Erdemci, Fikri; Yilmaz, Mehmet; Asir, Firat; Ozudogru, Osman; Deveci, Engin
    Background: COVID-19 pandemic has affected all the world. The consequence of the COVID-19 infection causes many disorders in many organs, one of them is the placenta. COVID-19 disease has long-term effects on various tissues after recovery. The aim of this study was to investigate the placentas of pregnant women with healthy, COVID-19 positive during the second trimester and labor. Material and methods: A total of twenty-four pregnant women (8 patients per each group) were included in the study. Their placentas were processed for routine paraffin wax embedding protocol. The blood parameters of patients were recorded. Placental tissues were stained with hematoxylin-eosin dye and immune stained with TNF-a and ADAMTS-8. Statistical analysis was performed on blood and histological parameters.Results: AST and CRP values of biochemical parameters were higher in women with second trimester and labor groups than in the healthy group. Also, a significant increase in ALT values was observed in the labor group. Normal histology was observed in the placentas of healthy patients. More histopathology was recorded in the placentas of COVID-19 infected women compared to healthy placentas. The expression of TNF-a and ADAMTS-8 were found significantly higher in the COVID-19 placentas compared to the non-COVID-19 group.Conclusions: COVID-19 infection can cause pathological changes during pregnancy and labor. This study shows that COVID-19 not only acutely has adverse effects on placental pathologies but also has long-term effects. TNF-a and ADAMTS-8 primary antibodies can be a guide in demonstrating these effects.
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    Biochanin A restored the blood-brain barrier in cerebral ischemia-reperfusion in rats
    (Assoc Medica Brasileira, 2024) Karaaslanli, Abdulmutalip; Asir, Firat; Gursoy, Gorkem Tutal; Tuncer, Mehmet Cudi
    OBJECTIVE: Blood-brain barrier is a protective layer that regulates the influx and efflux of biological materials for cerebral tissue. The aim of this study was to investigate the effects of Biochanin A on cerebral histopathology and blood-brain barrier immunohistochemically. METHODS: A total of 24 rats were assigned to three groups: sham, ischemia-reperfusion, and ischemia-reperfusion+Biochanin A. Ischemiareperfusion was performed by occluding the left carotid artery for 2/24 h. Notably, 20 mg/kg Biochanin A was administered to rats for 7 days after ischemia-reperfusion. Blood was collected for malondialdehyde and total oxidant/antioxidant status analysis. Cerebral tissues were processed for histopathology and further for immunohistochemical analysis. RESULTS: Malondialdehyde content with total oxidant status value was significantly increased and total antioxidant status values were significantly decreased in the ischemia-reperfusion group compared with the sham group. Biochanin A treatment significantly improved scores in the ischemiareperfusion+Biochanin A group. The normal histological appearance was recorded in the cerebral sections of the sham group. Degenerated neurons and vascular structures with disrupted integrity of the cerebral cortex were observed after ischemia-reperfusion. Biochanin A alleviated the histopathology in the cerebrum in the ischemia-reperfusion+Biochanin A group. Ischemia-reperfusion injury decreased the expression of blood-brain barrier in the ischemia-reperfusion group compared to the sham group. Administration of Biochanin A upregulated the blood-brain barrier immunoreactivity in the cerebrum by restoring blood-brain barrier. CONCLUSION: Cerebral ischemia-reperfusion caused an increase in oxidative stress and pathological lesions in the cerebrum. Biochanin A treatment restored the adverse effects of ischemia-reperfusion injury by restoring blood-brain barrier.
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    Comparison of testosterone, FSH, LH and E2 hormone levels in infertility suspected males with COVID-19 infection
    (Lippincott Williams & Wilkins, 2023) Ozkorkmaz, Ebru Gokalp; Basaran, Suereyya Ozdemir; Afsin, Muhamet; Asir, Firat
    Background: Coronavirus disease 2019 (COVID-19) is an infectious disease that has many adverse impacts on many systems including reproduction. The direct effects of COVID-19 on urogenital system are still open to argue. This study aimed to compare testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) hormone levels in COVID-19 infected male individuals with infertility suspicion.Methods: One hundred five control (healthy) and 105 COVID-19 infected males aged between 20 to 54 years old were enrolled in the study. All patients were either diagnosed with primary or secondary infertility suspicion. The COVID-19 infection was diagnosed via reverse-transcription polymerase chain reaction test. Blood samples from patients were analyzed from the control and COVID-19 group to measure serum testosterone, FSH, LH, and E2 levels. Hormone levels were statistically compared between groups with the Independent T test.Results: In control and COVID-19 patients, no significance was determined for FSH and LH hormone values. Testosterone hormone were significantly decreased and E2 level was statistically increased in COVID-19 patients compared to that in the control group (P < .001).Conclusion: COVID-19 is a viral disease that affects organ including gonads. COVID-19 infection decreased testosterone levels and increased E2 levels, which leading to disorders in male and female reproductivity.
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    Effects of Carvacrol on Experimental Testicular Torsion-Detorsion Model Investigation by Immunohistochemistry
    (Sci Printers & Publ Inc, 2020) Dursun, Recep; Sen, Abdullah; Yaman, Mahmut; Durgun, Hasan Mansur; Asir, Firat
    OBJECTIVE: To investigate the protective effects of carvacrol on an experimental testicular torsion-detorsion rat model. STUDY DESIGN: Wistar male rats (n=48) weighing 230-250 g were assigned to 4 groups (8 per group): control, torsion, torsion-detorsion, and torsion-detorsion + carvacrol-treated groups. Control group animals did not undergo any surgical operation. For the torsion group, the scrotum was opened (under general anesthesia) and the left testis twisted 720 degrees clockwise and in the last 30 minutes of 3-hour ischemia; i.p. saline was injected. In the torsion-detorsion group, after ischemia the left testis was reperfused for 2 hours. The torsion/ detorsion +carvacrol group protocol was similar to that of the torsion-detorsion group but in the last 30 minutes of 3-hour ischemia, i.p. 20 mg/kg carvacrol was administered. RESULTS: Malondialdehyde (MDA) was highest in the torsion-detorsion group (p <0.01). The lowest catalase (CAT) value was found in the torsion-detorsion group. Decrease in glutathione (GSH) levels of the torsion and torsion-detorsion groups as compared to those of control and carvacrol groups was significant (p<0.01). The highest superoxide dismutase (SOD) value was in the control and carvacrol groups. Increased apoptosis and degeneration of spermatogenic cells with hyperplasic nuclei were mainly observed in the torsion and torsion-detorsion groups. The torsion-detorsion + carvacrol group mostly showed regular histology, but Leydig cells were degenerated. ET-1 expression was increased in endothelial cells in the torsion and detorsion groups but negative in the carvacrol group. Bax expression was positive in luminal spermatogenic cells in the torsion group but negative in interstitial cells in both torsion and torsion-detorsion groups. In the carvacrol-treated group some luminal spermatogenic cells in seminiferous tubules showed positive Bax expression but weak in basal membrane cells and Leydig cells. CONCLUSION: Carvacrol influences spermatogenic cells with strong mitotic activity in basal membranes of seminiferous tubules and may prevent apoptotic development and signaling of these cells.
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    Gallic acid showed neuroprotection against endoplasmic reticulum stress in rats
    (Acta Cirurgica Brasileira, 2025) Karaaslanli, Abdulmutalip; Tuncer, Mehmet Cudi; Asir, Firat; Korak, Tugcan
    Purpose: We aimed to investigate the role of gallic acid treatment on spinal cord tissues after spinal cord injury (SCI) and its relationship with endoplasmic reticulum (ER) stress by histochemical, immunohistochemical, and in-silico techniques. Methods: Thirty female Wistar albino rats were divided into three groups: sham, SCI, and SCI+gallic acid. SCI was induced by dropping a 15-g weight onto the exposed T10-T11 spinal cord segment. The SCI+gallic acid group received 25 mg/kg of gallic acid intraperitoneally daily for one week. Histopathological, immunohistochemical, and silico analyses were performed. Results: Histological analysis revealed improved neural cell survival and tissue integrity in the SCI+gallic acid group compared to the SCI group. Caspase-12 expression was significantly increased in the SCI group, indicating elevated ER stress and apoptosis. Gallic acid treatment resulted in a marked reduction in caspase-12 expression in neurons, neuroglia, and endothelial cells, suggesting decreased ER stress. Conclusion: Gallic acid exhibits significant neuroprotective effects against ER stress and cellular damage in a rat model of SCI. The in-silico analysis revealed apoptotic and immune-related pathways in which gallic acid showed neuroprotective effects by regulating caspase-12. These results suggest that gallic acid may be a promising therapeutic agent for mitigating secondary damage post-SCI.
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    Ganoderma Lucidum Alleviates Ischemia- Reperfusion-Induced Renal Injury in Wistar Rats
    (Sci Printers & Publ Inc, 2021) Donder, Ahmet; Asir, Firat
    OBJECTIVE: To investigate effects of Ganoderma lucidum (G. lucidum) kidney sections of rats induced by ischemia-reperfusion (I/R) injury. STUDY DESIGN: A total of 40 rats were assigned to 4 groups: control (Sham), I/R, G. lucidum, and I/R+ G. lucidum groups. Prior to animal experiments, 20 mL/kg G. lucidum was administered to the G. lucidum-treated groups for 7 days. The control and 1/R groups received only saline solution. The kidney was exposed to hypoxia for 1 hour by clamping renal vessels and was then allowed to reoxygenate for 6 hours. Blood was taken to measure for serum MDA, MPO, and GSH. Kidney tissues were resected for histological paraffin tissue protocol. Hematoxylin-eosin and immunohistochemical staining were performed. RESULTS: MDA and MPO levels were highest in the I/R group but were close to the levels of the control group in the I/R+G. lucidum group. Unlike MDA and MPO values, GSH values were the lowest in the I/R group, but after G. lucidum treatment, GSH levels increased in the I/R+ G. lucidum group. In kidney sections of hematoxylin-eosin staining, the control group showed no pathology. In the I/R group, atrophic glomeruli, degenerated tubular cells, and mononuclear cell infiltration with dilated and congested vessels were observed. In the I/R+ G. lucidum group, I/R pathology was mostly recovered. In the G. lucidum group, ADAMTS-4 expression was moderately expressed in glomerular and tubular cells. The I/R group showed positive ADAMTS-4 expression in mostly inflammatory cells. In the I/R+ G. lucidun: group, ADAMTS-4 was positively expressed only in glomerular structures. In the G. lucidum group, caspase-3 expression was observed in glomerular and tubular cells. The I/R group showed strong caspase-3 activity in glomerular and tubular cells, in vascular cells, and inflammatory cells. The I/R +G. lucidum group showed weak caspase-3 expression. CONCLUSION: Ischemia-reperfusion injury caused histopathological and biochemical alterations in renal tissue; G. lucidum protected tissue structure and integrity by its antioxidant and anti-inflammatory properties.
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    Hesperidin May Protect Gastric Tissue Against Immobilization Stress
    (Sci Printers & Publ Inc, 2021) Beskisiz, Songul; Asir, Firat
    OBJECTIVE: To investigate antioxidant properties of hesperidin against gastric lesions in immobilized rats with immunostaining of caspase-3 and IL-10. STUDY DESIGN: Thirty male Wistar albino rats were assigned to control, stress, and stress+ hesperidin groups. Immobilization stress was created by rodent restrainers lined with an absorbent pad. Immobiliza-tion cones were secured using 2 strips of clear packing tape and laboratory tape wrapped around the base of the tail solely to cue release from the restrainer. The control group was administered isotonic saline solu-tion for 14 days. The stress group was systematically immobilized 3 hours per day for 14 consecutive days using rodent restrainers. One hour before immobiliza-tion stress, 30 mg/kg hesperidin was administered for 14 days in the stress+ hesperidin group. Blood samples were taken from the animals for biochemical mark-ers MDA, GSH-Px, and MPO. Gastric tissues were processed for routine histological paraffin wax embedding. Five-mu m-thick sections were obtained from paraffin blocks and stained with hematoxylineosin caspase-3 and IL-10 immunostaining. RESULTS: Compared to the control group, MDA and MPO values were higher and GSH content was lower in the stress group, but hesperidin treatment restored these values close to those of the control groups. His-tologically, the control group showed no pathology. The stress group showed degenerative nuclei, lymphocyte accumulation, vascular dilation/congestion, and hyperplasic muscle. In the stress+ hesperidin group, most pathology observed in the stress group was restored.Caspase-3 expression was mostly negative in the control group, while positive reaction was observed in sur- face epithelial cell nuclei and gastric gland nuclei in the stress group. In the stress+ hesperidin group, caspase-3 expression was positive in some cells and glands. In the control group, IL-10 expression was negative, while dense IL-10 expression was observed in the nuclei and cytoplasm of surface epithelial cells, in the foveola gas- tric, in glandular cells in the stress group. In the stress + hesperidin group, IL-10 expression was only positive in some solitary leukocytes and cells around the vessel. CONCLUSION: It was observed that anaphylactic administration of hesperidin causes a decrease in lipid peroxidation and inflammation, thus promoting cell survival and partially preventing structural and integrity of gastric tissue.
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    The Immunohistochemical and Bioinformatics Analysis of the Placental Expressions of Vascular Cell Adhesion Protein 1 (VCAM-1) and High Mobility Group Box 1 (HMGB1) Proteins in Gestational Diabetic Mothers
    (Georg Thieme Verlag Kg, 2024) Oglak, Suleyman Cemil; Asir, Firat; Yilmaz, Emine Zeynep; Bolluk, Gokhan; Korak, Tugcan; Agacayak, Elif
    Objective We aimed to examine both the expression levels of high mobility group box 1 (HMGB1) and vascular cell adhesion molecule-1 (VCAM-1) proteins in the placentas of pregnant women with gestational diabetes mellitus (GDM) and control groups by immunohistochemical (IHC) method. Material and methods An experimental case-control study was conducted, including 40 pregnant women complicated with GDM and 40 healthy pregnant women. Placental tissues obtained following cesarean delivery were subjected to routine tissue monitoring. The placental sections were stained with VCAM-1 and HMGB1 immunostains and subjected to IHC examination under a light microscope. H-score (HS) was used to evaluate the results of IHC staining by semi-quantitative analysis. Pathway analysis in Cytoscape software identified GDM-associated proteins within HMGB1 and VCAM-1 interaction networks, followed by GO analysis to explore associated biological processes. Results Placental HGMB1 expression was significantly increased in the GDM group compared to the control group (p<0.001). However, placental VCAM-1 expression was found to be statistically similar in GDM and control groups (p=0.584). The shared 19 proteins were identified between HMGB1 and GDM, and 13 between VCAM-1 and GDM, with notable GO biological process terms such as immune system activation for HMGB1 and interleukin-6 regulation for VCAM-1 associated with GDM. Conclusion We consider that GDM-related inflammation and oxidative stress may contribute to tissue damage and inflammation by increasing placental HMGB1 expression. The blockade of HMGB1 and its receptors might represent a promising therapeutic approach to control inflammation in GDM. Understanding the distinct roles of HMGB1 and VCAM-1 may provide valuable insights for the development of targeted therapies aimed at mitigating the inflammatory processes associated with GDM and improving maternal and fetal outcomes.
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    The Investigation of Caspase-3 and Tumor Necrosis Factor-Alpha Expression in Placentas of Patients with Preterm Premature Rupture of Membranes
    (Imr Press, 2023) Ermis, Isilay Sezen; Asir, Firat; Oglak, Suleyman Cemil; Kaplan, Ozge; Aydeniz, Gul Ebru; Deveci, Engin
    Background: Caspase-3 is involved in the execution of apoptosis and is widely used as an apoptotic marker. Tumor necrosis factor-& alpha; (TNF-& alpha;) released from activated macrophages has various functions such as modulation of cell growth and differentiation, immunoreg-ulation, coagulation, and regulation of endothelial cell function. This study investigated the immunohistochemical staining of caspase-3 and TNF-& alpha; expression in the placentas of pregnant women with preterm premature rupture of membranes (PPROM). Methods: Placen-tas of 25 healthy, and 25 women with PPROM were processed for routine histological tissue processing. Placentas were stained with hematoxylin-eosin, caspase-3, and TNF-& alpha; immunostaining. Results: Normal placental histology was observed in the control group. Amniotic epithelium, vascular structures, and fibrinoid accumulation were histologically normal. Leukocyte infiltration, thinned vessel walls with dilatation and congestion, syncytial nodes, and fibrinoid accumulation were increased in the PPROM group. The immune activity of caspase-3 expression was mainly negative in placental components such as syncytial nodes, vascular endothelium, fibrinoid accumulation, and macrophages in the control group. In the PPROM group, caspase-3 positive reaction was increased in the amniotic membrane and epithelium, endothelial cells, fibrinoid accumulation, and areas of inflammatory cell infiltration. In the control group, negative TNF-& alpha; expression was observed in the placental membranes and structures. In the PPROM group, TNF-& alpha; expression was in-creased in inflammatory cells, endothelial cells, and syncytial nodes. Conclusions: Placentas of patients with PPROM showed loss and weakened membranes with increased placental pathology, and increased expression of caspase-3 and TNF-& alpha;. We suggest that caspase-3 and TNF-& alpha; signaling pathways can be used as a marker in the progression of PPROM.
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    Investigation of the Effects of Carvacrol on Experimental Ischemia/Reperfusion Model of Rat Ovaries by Immunohistochemistry
    (Sci Printers & Publ Inc, 2020) Peker, Nurullah; Deger, Ugur; Asir, Firat
    OBJECTIVE: Ovarian torsion is a gynecologic problem that presents as acute lower abdominal pain. As a result, blood flow to the ovaries decreases and ischemia develops. Many medications have been used to treat ovarian torsion, including carvacrol. We conducted an experimental ischemia/reperfusion (torsion-detorsion) model using rats to observe the effects of carvacrol on ovarian torsion by immunohistochemical study. STUDY DESIGN: Thirty-two female Wistar rats were randomly categorized into 4 groups (8 rats per group): control group, ischemia group, ischemia/reperfusion group, and ischemia/reperfusion + carvacrol-treated group. Ischemia was created by sealing the left ovaries for 3 hours, followed by 3-hour reperfusion. For the ischemia/reperfusion + carvacrol-treated group, 100 mg/kg carvacrol was administered orally in 2 mL 0.9% NaCl after the reperfusion. All animals were sacrificed, and ovarian tissues were dissected for routine paraffin wax embedding tissue protocol. RESULTS: Control groups showed normal ovarian histological structures. In the ischemia group, hyperplastic granulosa cell vascular dilation, severe hemorrhage, and inflammation were observed. The ischemia/reperfusion group showed edema, inflammation, congestion, degenerated follicles, and cells with pyknotic nuclei. In the ischemia/reperfusion + carvacrol group, degenerative changes and vascular pathologies were decreased in ovarian tissues. Endothelin-1 (ET-1) was expressed in degenerated follicles and vascular endothelial cells in the ischemia and ischemia/reperfusion group. Expression of ET-1 was decreased in follicular cells but negative in stromal and luteal cells in the ischemia/reperfusion + carvacrol group. ADAMTS-5 expression was positive in degenerated follicles, apoptotic cells, and inflammatory cells in the ischemia and ischemia/reperfusion groups. In the ischemia/reperfusion + carvacrol group, corona cells and a few inflammatory cells around vessels showed positive ADAMTS-5 expression. CONCLUSION: ET-1 can induce angiogenic development with the decrease of degenerative development and inflammation in the carvacrol group. ADAMTS-5 molecule may be a marker of cellular structure and extracellular matrix development in different stages of development of ovarian cells and follicles in ischemia and oxygen deficiency caused by ischemia reperfusion.
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    Investigation of Vitamin D Levels in Men with Suspected Infertility
    (Mdpi, 2024) Asir, Firat; Duran, Senem cetin; Afsin, Muhammet; Duran, Enis; Korak, Tugcan; Sahin, Firat
    Male infertility may be caused by an impaired sperm functionality, with insufficient vitamin D levels affecting the quantity and development of motile sperm. Given the influence of vitamin D on vital aspects of male infertility, this study aimed to investigate the correlation between vitamin D levels and male infertility, along with exploring the possible mechanism of action. A total of 306 male participants were included. Semen samples were collected and analyzed for semen parameters with demographic features. Patients were classified into two groups based on vitamin D levels of <20 ng/mL (low) and >= 20 ng/mL (high). The Super-PRED, Swiss TargetPrediction, GeneCards, and DisGeNET databases were utilized to retrieve potential molecular targets associated with both vitamin D and male infertility, while the STRING database was employed for constructing protein-protein interaction (PPI) networks and conducting a functional enrichment analysis. A total of 146 patients (47.71%) showed low vitamin D levels and 160 patients (52.29%) had high vitamin D levels. Vitamin D was not strongly influenced by demographic parameters. Vitamin D demonstrated significant positive correlations with type A and B sperm motility. Conversely, it exhibited significant negative correlations with type C and D sperm motility. Hormones (thyroid-stimulating hormone, follicle-stimulating hormone, prolactin, luteinizing hormone, estradiol) were not significantly associated with vitamin D; however, testosterone was significantly positive correlated with vitamin D. Notably, no significant correlation was found between vitamin D levels and iron, ferritin, hemoglobin, hematocrit, calcium, magnesium, and phosphorus levels. The functional annotations of potential vitamin D targets associated with male infertility primarily indicated involvement in regulating infection, the immune response, forkhead box O (FOXO) and hypoxia-inducible factor 1 (HIF1) signals in male infertility. Adequate vitamin D levels are associated with an improved reproductive health, evidenced by positive correlations with hormone levels and sperm motility. Specifically, the FOXO and HIF-1 signaling pathways may be effective in the potential molecular mechanisms underlying the impact of vitamin D on male infertility and/or in the significant correlations identified.
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    Neuroprotective Effects of Potentilla Fulgens on Traumatic Brain Injury in Rats
    (Sci Printers & Publ Inc, 2017) Ozevren, Huseyin; Irtegun, Sevgi; Deveci, Engin; Ozgur, Mustafa Esref; Asir, Firat; Tekin, Mehmet Ali; Deveci, Senay
    OBJECTIVE: To investigate if Potentilla fulgens (P. fulgens) has any neuroprotective effects on traumatic brain injury in rats. STUDY DESIGN: Sprague-Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g(-1) m weight-height impact. Sixty-four rats were divided into 4 groups: group 1 (vehicle-treated control), group 2 (P. fulgens 400 mg/kg/day, intraperitoneally [i.p.]), group 3 (vehicle-treated trauma), and group 4 (trauma+P. fulgens 400 mg/kg/day, i.p.). Distilled water was used as vehicle. All rats were decapitated 5 days after the induction of trauma, and the protective effects of P. fulgens were evaluated by histological, immunohistochemical, and biochemical analyses. RESULTS: Administration of P. fulgens at a dose of 400 mg/kg/day provided significant improvement in all of the histological, biochemical, and immunohistochemical analyses after the induction of traumatic brain injury. CONCLUSION: Although further studies are necessary to evaluate the time-and dose-dependent neuroprotective effects of P. fulgens, it may be a beneficial therapeutic agent for prevention of secondary neuronal damage following diffuse traumatic brain injury.
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    Protective Effect of Sildenafil on the Heart in Hepatic Ischemia/Reperfusion Injury
    (Sci Printers & Publ Inc, 2021) Ekinci, Aysun; Oguz, Abdullah; Asir, Firat; Ekinci, Cenap; Dursun, Recep
    OBJECTIVE: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats. STUDY DESIGN: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+ SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+ SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically. RESULTS: Serum MDA levels were elevated significantly in the IR and IR+ SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+ SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+ SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase. CONCLUSION: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+ SIL groups.
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    Protective effects of passiflora incarnata on ovarian ischemia/reperfusion damage in rats with ovarian torsion
    (Turkish Assoc Trauma Emergency Surgery, 2023) Arslan, Serkan; Asir, Firat; Ozkorkmaz, Ebru Gokalp; Azizoglu, Mustafa; Basuguy, Erol; Okur, Mehmet Hanifi; Otcu, Serap Mutlu Ozcelik
    BACKGROUND: This study aimed to investigate whether Passiflora Incarnata (PI) has a protective effect against ischemia-reperfusion (IR)-induced oxidative and inflammatory ovarian damage. METHODS: The effects of PI on ovarian ischemia-reper fusion injury were investigated in female Wistar albino rats. The animals were randomly divided into three groups: Group 1 (sham), Group 2 (IR), and Group 3 (IR+PI). RESULTS: The mean levels of Malondialdehyde (MDA), Myeloperoxidase (MPO), and Total Oxidant Status (TOS) were higher in the IR group (p=0.025, p<0.001, and p=0.016, respectively). The Total Antioxidant Status (TAS) levels were lower in the IR group (p=0.005). Immunostaining revealed significant differences across the groups for Tumor necrosis factor-alpha (TNF-alpha): 13.84%, 49.51%, and 22.51% for Groups 1, 2, and 3, respectively (p<0.01). Bax: 10.53%, 46.74%, and 26.46% for Groups 1, 2, and 3, respectively (p<0.01). Annexin V: 12.24%, 44.86%, and 23.28% for Groups 1, 2, and 3, respectively (p<0.01). The mean scores for hemorrhage, inflammation, follicular degeneration, and congestion showed significant variations among the groups, all registering p<0.001. CONCLUSION: Passiflora Incarnata exhibited antioxidant, anti-inflammatory, and anti-apoptotic properties, promoting cell survival, histologically protecting ovarian tissue, and ameliorating IR injury by reducing oxidative stress.
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    Quality by Design approach for developmentand characterization of gabapentin-loaded solid lipid nanoparticles for intranasal delivery: In vitro, ex vivo , and histopathological evaluation [2]
    (Mashhad Univ Med Sciences, 2024) Toksoy, Mahmut Ozan; Asir, Firat; Guzel, Mert Can
    Objective(s): Quality by Design (QbD) is a novel approach to product development that involves understanding the product and process, as well as the relationship between critical quality attributes (CQA) and critical process parameters (CPP). This study aimed to optimize the gabapentin-loaded solid lipid nanoparticle formulation (GP-SLN) using a QbD approach and evaluate in vitro and ex vivo performance. Materials and Methods: The GP-SLN formulation was created using the microemulsion method by combining Gelucire 48/16, Tween 80, and Plurol Oleique CC 497. The Box-Behnken experimental design was adopted to investigate the effects of independent factors on dependent factors. The GPSLN formulation was assessed based on particle size and distribution, zeta potential, morphology, entrapment efficiency, release kinetics, permeation parameters, stability, and nasal toxicity. Results: The nanoparticles had a cubical shape with a particle size of 185.3 +/- 45.6 nm, a zeta potential of -24 +/- 3.53 mV, and an entrapment efficiency of 82.57 +/- 4.02%. The particle size and zeta potential of the GP-SLNs remained consistent for 3 months and followed Weibull kinetics with a significantly higher ex vivo permeability (1.7 fold) than a gabapentin solution (GP-SOL). Histopathology studies showed that intranasal administration of the GP-SLN formulation had no harmful effects. Conclusion: The current study reports the successful development of a GP-SLN formulation using QbD. A sustained release of GP was achieved and its nasal permeability was increased. Solid lipid nanoparticles with optimum particle size and high entrapment efficiency may offer a promising approach for the intranasal delivery of drugs.