Browsing by Author "Aktug H."

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    Evaluation of the relationship between inducible nitric oxide synthase (iNOS) activity and effects of melatonin in experimental osteoporosis in the rat
    (2006) Oktem G.; Uslu S.; Vatansever S.H.; Aktug H.; Yurtseven M.E.; Uysal A.
    Inducible nitric oxide synthase (iNOS) plays a critical role in the pathogenesis of osteoporosis. iNOS generates nitric oxide (NO), a free radical contributing to the imbalance between bone formation and resorption caused by estrogen depletion. Melatonin is the major product of the pineal gland which is known to diminish iNOS expression and NO production significantly. The aim of this study was to determine the distribution of iNOS and the amount of apoptotic cells after melatonin treatment in ovariectomized rats. Since previous studies have shown that constitution of bone formation is primarily sustained in nucleus pulposus and epiphyseal cartilage, experiments were carried out on nucleus pulposus and epiphyseal cartilage; additional quantitation of osteoblasts and osteoclasts were evaluated on vertebral area as well. Vertebral sections of ovariectomized rats were obtained from formalin-fixed and parafin-embedded blocks. iNOS expression and quantitation of apoptotic cells in nucleus pulposus and epiphyseal cartilage were evaluated using indirect immunoperoxidase and TUNEL techniques, respectively. The number of osteoclasts and osteoblasts in trabecular bone was determined using histomorphometry. Ovariectomy increased iNOS expression and the number of apoptotic cells in nucleus pulposus and epiphyseal cartilage, whereas a 4-week treatment with melatonin (10 mg/kg/day) resulted in the reduction of both effects. These data indicate that there is strong influence of melatonin application on expression of iNOS, apoptosis, osteoclast and osteoblast numbers after ovariectomy. In conclusion, melatonin besides its usual use as an antiaging hormone, may also be an effective hormone in treatment of bone changes in estrogen deficiency states. © Springer-Verlag 2006.
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    Ovarian failure in diabetic rat model: Nuclear factor-kappaB, oxidative stress, and pentraxin-3
    (Elsevier Ltd, 2014) Erbas O.; Pala H.G.; Pala E.E.; Oltulu F.; Aktug H.; Yavasoglu A.; Taskiran D.
    Objective: The aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models. Materials and methods: An experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-κB immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Müllerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann-Whitney U and χ2 tests. Results: We found statistically significantly lower glutathione and anti-Müllerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration, stromal fibrosis scores, and NF-κB immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups. Conclusion: These findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-κB pathway with resveratrol. We thought that the NF-κB pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Müllerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further. © 2014.
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    The protective effect of granulocyte colony-stimulating factor on endometrium and ovary in a rat model of diabetes mellitus
    (S. Karger AG, 2014) Pala H.G.; Pala E.E.; Artunc Ulkumen B.; Aktug H.; Yavasoglu A.; Korkmaz H.A.; Erbas O.
    Aims: To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on the endometrium and ovaries in an experimental diabetes mellitus (DM) rat model. Methods: A total of 18 female Sprague-Dawley albino mature rats (8 weeks, 200-220 g) were used in this study. Diabetes was induced by intraperitoneal (i.p.) injection of streptozocin randomly in 12 rats. No drug was administered to the remainder of the rats (control group, group 1, n = 6). The other 12 rats were randomly divided into 2 groups; 1 ml/kg i.p. saline was given as vehicle to group 2 (diabetic nontreated control group, n = 6) and 100 μg/kg/day of i.p. G-CSF was given to group 3 (G-CSF-treated group, n = 6) for 4 weeks. After 4 weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Results: The mean endometrial gland degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Ovarian follicle degeneration, stromal degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Plasma TGF-β and malondialdehyde levels were significantly lower in groups 1 and 3 compared with group 2. Antimüllerian hormone levels were significantly lower in group 2 compared with groups 1 and 3. Conclusion: Glucose toxicity occurred severely in the ovaries and endometrium of the DM rats. After G-CSF treatment, ovarian and endometrial injury and fibrosis scores decreased significantly. The effects of G-CSF in rat models give hope to improved treatment of human DM complications such as premature ovarian failure and endometrial dysfunction. © 2014 S. Karger AG, Basel.
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    Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: An experimental rat model study
    (Informa Healthcare, 2015) Erbas O.; Pala H.G.; Pala E.E.; Artunc Ulkumen B.; Akman L.; Akman T.; Oltulu F.; Aktug H.; Yavasoglu A.
    The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given)-Group-2 and sunitinib treatment group-Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann-Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans. © 2015 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.
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    JAK/STAT pathway interacts with intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) while prostate cancer stem cells form tumor spheroids
    (Zerbinis Publications, 2015) Duzagac F.; Inan S.; Simsek F.E.; Acikgoz E.; Guven U.; Khan S.A.; Rouhrazi H.; Oltulu F.; Aktug H.; Erol A.; Oktem G.
    Purpose: JAK/STAT is an evolutionarily conserved pathway and very important for second messenger system. This pathway is important in malignant transformation and accumulated evidence indicates that this pathway is involved in tumorigenesis and progression of several cancers. It was possible to assume that activation of JAK/STAT pathway is associated with increase in the expressions of ICAM-1 and VCAM-1. In this study we hypothesized that when cells were maintained as spheroids or monolayers, the structure of cancer stem cells (CSCs) could show differentiation when compared with non-CSCs. Methods: DU-145 human prostate cancer cells were cultured using the Ege University molecular embryology laboratory medium supplemented with 10% fetal bovine serum. Clusters of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 cell line by using BD FACSAria. CD133+/CD44+ CSCs were cultured until confluent with 3% noble agar. The expression of these proteins in CSCs and non-CSCs was analyzed by immunohistochemistry. Results: Different expression profiles were observed in the conventional two-dimensional (2D) and three-dimensional (3D) experimental model system when CSCs and non-CSCs were compared. Human prostate CSCs exhibited intense ICAM-1 and VCAM-1 immunoreaction when compared with non-CSCs. These findings were supported by the fact that VCAM-1 on the surface of cancer cells binds to its counterreceptor, the a4fil integrin (also known as very-late antigen, VLA-4), on metastasis-associated macrophages, triggering VCAM-1-mediated activation of the phosphoinositide 3-kinase growth and survival pathway in cancer cells. Conclusions: The results of this study showed that changes in JAK/STAT pathway are related with adhesion molecules and could affect cancer progression.
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    Histological investigation of experimentally induced diabetes effects on the distribution of transforming growth factor (TGFβ), nuclear factor kappa b (NF-κb), heat schock 90β (hsp90β) and e-cadherin proteins in testicular tissue; [Investigación histológica de los efectos de la diabetes inducida experimentalmente en la distribución del factor de crecimiento transformante (TGFβ), nuclear factor kappa b (NF-κb), y proteinas heat schock 90β (hsp90β) y e-cadherina en tejido testicular]
    (Universidad de la Frontera, 2021) Toros P.; Oltulu F.; Tuglu I.; Uysal A.; Özçinar E.; Turgan N.; Rouhrazi H.; Aktug H.
    Diabetes is a metabolic disorder characterized by high blood sugar levels and it causes complications in many systems, including the reproductive system. As a result of diabetic conditions, one of the mechanisms that can cause repression of reproductive activity is testicular oxidant stress. The identification of diabetes on the cell signaling molecules axis is still under discussion. The aim of this study was to determine the effect of Transforming Growth Factor (TGFβ), Nuclear Factor kappa B (NF-κB), Heat-schock 90β (HSP90β) signal pathways and E-cadherin cell adhesion molecule on infertility in diabetic rat testicular tissue. In our study, includes histological, molecular and biochemical analysis of testicular tissue removed at the end of the 2 weeks experiment period. A total of 14 adult male rats were divided as control and diabetes. No intervention was given to 7 male rats in the control group. For the diabetic group, 7 male rats were injected by intraperitoneal with a single dose of 55 mg/kg streptozotocin (STZ). TGFβ, NF-κB, HSP90β and E-cadherin proteins were immunohistochemically studied to investigate possible tissue damage, inflammatory process, cell stabilization and integrity due to diabetes. In order to determine oxidant stress, lipid peroxidation product malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GPx) analyzes were performed. Fibrosis, inflammatory changes and loss of spermatogenetic series are prominent findings in the diabetic group. On analysis of all the samples with immunostaining, in the diabetic group, TGFβ and NF-κB immunoexpression significantly increased, while Hsp90β and E-cadherin immunoexpression significantly decreased compared with control groups. Experimental diabetes was found to cause fibrosis, inflammation, disrupting cell adhesion and stabilization in testicular tissue. These results suggest that cellular therapy studies are needed for possible damage. © 2021, Universidad de la Frontera. All rights reserved.