Browsing by Author "Erbas, O"

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    The effectiveness of different neuroprotective agents in facial nerve injury: An experimental study
    Tanyeri, G; Celik, O; Erbas, O; Oltulu, F; Dilsiz, OY
    Objectives/Hypothesis To examine and compare the neuroprotective effects of dexamethasone, oxytocin, and resveratrol administration on regeneration after facial nerve crush injury in a rat model. Study Design Prospective, randomized, controlled animal study. Methods A crush-type facial nerve injury was performed on the right side of all rats (injury group [IG]), whereas there was no injury on the left side (sham group [SG]). These main groups were divided into five subgroups: 1) no medicine (control); 2) physiological serum; 3) dexamethasone; 4) oxytocin; and 5) resveratrol (Res) administered (intraperitoneal injection) for 28 days. Functional recovery was evaluated by daily eye-blink reflex and facial electromyography. Nerve-muscle degeneration and regeneration, apoptosis, and intercellular connections were evaluated in histopathological and immunohistochemical examinations. Results Recovery time of the postinjury eye-blink reflex demonstrated faster recovery in IG + Res when compared with the other subgroups. In peak-to-peak amplitude values, a significant increase was observed in the dexamethasone (P = 0.007) and oxytocin subgroups (P = 0.004) and was even more apparent in the resveratrol subgroup (P < 0.001). Nerve regeneration is apparent in the resveratrol subgroup. Apoptotic changes were evaluated immunohistochemically with TUNEL and Caspase 3 and 6 antibodies staining. Caspase 3 and 6 immunoexpressions of resveratrol and oxytocin subgroups were moderate when compared with dexamethasone subgroup. Except for the resveratrol subgroup, which had an increase in expression, the majority of subgroups were similar to SG in terms of intercellular connections (Connexin 32 and 43). Conclusion Resveratrol leads to the best outcome after facial nerve crush injury in rats when compared with dexamethasone and oxytocin, even though these agents demonstrate a significant improvement in facial nerve regeneration.
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    Protective effects of dichloroacetic acid on endometrial injury and ovarian reserve in an experimental rat model of diabetes mellitus
    Pala, HG; Pala, EE; Ulkumen, BA; Erbas, O
    Aim To study (1) ovarian and endometrial damage caused by the hyperglycemia and (2) the effects of dichloroacetic acid (DCA) on follicular reserve and endometrial damage in streptozocin induced diabetic rats. Methods This study consisted 24 rats randomly separated into three groups. A diabetes model was achieved in 16 rats experimentally, and normoglycemic eight rats were assigned as control group (Group 1). The rats with diabetes were randomly separated to two groups: 1 mL/kg/day intraperitoneal 0.9% NaCl was given to eight rats as diabetic vehicle (Group 2) and 10 mg/kg/day DCA was given to other eight rats as DCA treated group (Group 3). Hysterectomy with bilateral oophorectomy was performed for histopathological evaluation and blood samples were collected after 4 weeks. Results Diabetes caused ovarian and endometrial damage (p < 0.0001). Pentraxin-3 (PTX-3), lactic acid, and transforming growth factor-beta (TGF-beta) were higher (p < 0.05, p < 0.05, and p < 0.0001, respectively), whereas anti-Mullerian hormone (AMH) was lower in diabetic rats (p < 0.05). These findings reflected the diabetic damage in the genital tract and diminished ovarian reserve occurred via fibrosis, severe inflammation, and oxidative stress. DCA improved the histopathological fibrosis and degeneration in the ovaries and endometrium (p < 0.05). There was a concominant decrease of TGF-beta and lactic acid levels with DCA treatment (p < 0.05). DCA also improved ovarian reserve with higher AMH levels (p < 0.05). Conclusions The several unfavored changes in the endometrium and ovaries due to diabetes have been determined in this present study. DCA might provide the continuity of the endometrial cycle, physiological endometrial structure, ovarian follicular growth, oocyte maturation, and physiological ovarian function by decreasing the lactate levels via inhibiting pyruvate dehydrogenase kinase enzyme.
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    Comparison of Nephron-protective Effects of Enalapril and GLP Analogues (Exenatide) in Diabetic Nephropathy
    Çavusoglu, T; Erbas, O; Karadeniz, T; Akdemir, O; Acikgoz, E; Karadeniz, M; Tuglu, MI; Ates, U
    Background: One of the major concerns is a nephropathy in diabetes, which applies many different kinds of medicines. However, required level of the treatment of renal disease has not been achieved. Aim: To investigate and compare the effect of the enalapril and the exenatide on diabetic nephropathy in rats developed diabetes by streptozosin. Material and Methods: 32 male Sprague Dawley rats were divided into 4 groups: (1) Control, (2) Diabetic (DM), (3) DM + Enalapril, and (4) DM + exenatide groups. Then, the animals were euthanized and their blood samples were collected by cardiac puncture for blood glucose; blood urea nitrogen (BUN), creatinin, and nephrectomy were performed for histopathologic examination, and urine samples were taken on stick for proteinuria. Results: Administration of the enalapril or the exenatide in diabetic rats resulted in a significant reduction both fibronectin, induced nitric oxide synthase (i-NOS) expression in glomerular area and urine protein levels. It was shown that both of enalapril and exenatide protected the renal glomerulus more than diabetic group in the nephropathy histopathologically. Conclusion: The beneficial effects of enalapril and exenatide which reduces fibronectin, i-NOS expression and urine protein levels or increases recovery of glomerules, might be used for preventing the harmful effects of diabetic nephropathy.
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    Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy
    Karadeniz, T; Cavusoglu, T; Turkmen, E; Uyanikgil, Y; Karadeniz, M; Akdemir, O; Tuglu, MI; Ates, U; Erbas, O
    Hyperglycemia, hypertension, dyslipidemia, and inflammation have been proposed to account for the development of nephropathy in diabetic subjects. The beneficial effects of enalapril on diabetic nephropathy are known. However, the effects of trimetazidine (TMZ) are still unknown. We aimed at comparing the effects of the enalapril and TMZ treatment on fibronectin expression, inducible nitric oxide synthase expression, urine proteinuria, blood glucose and glomerular, and mesangial structures of kidney in rats that take streptozotocin (STZ). In this study, 32 male Sprague-Dawley albino mature rats of 8 weeks, weighing 200-220 g were used. Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg) for 24 rats. We made four groups (Group 1: control, non-diabetic rats (n = 8), Group 2: diabetes, without treatment (n = 8), Group 3: diabetes treatment with enalapril (n = 8), Group 4: diabetes treatment with TMZ (n = 8). The positive effects of renal tissue and tubules in the mesangium immunohistochemical were shown in TMZ receiving rat groups. These positive effects were in parallel with the reduction in fibronectin and I-NOS expression and reduction in the proteinuria. TMZ and enalapril treatment of diabetic rats and renal parenchyma in this study are shown to have positive effects on the different levels.
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    The Protective Effect of Granulocyte Colony-Stimulating Factor on Endometrium and Ovary in a Rat Model of Diabetes Mellitus
    Pala, HG; Pala, EE; Ulkumen, BA; Aktug, H; Yavasoglu, A; Korkmaz, HA; 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 intra peritoneal (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 mu g/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-beta and malondialdehyde levels were significantly lower in groups 1 and 3 compared with group 2. Antimullerian 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. (C) 2014 S. Karger AG, Basel
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    Ovarian failure in diabetic rat model: Nuclear factor-kappaB, oxidative stress, and pentraxin-3
    Erbas, O; Pala, HG; Pala, EE; 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)-kappa B immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Mullerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann-Whitney U and X-2 tests. Results: We found statistically significantly lower glutathione and anti-Mullerian 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-kappa B 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-kappa B pathway with resveratrol. We thought that the NF-kappa B 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-Mullerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
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    Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study
    Erbas, O; Pala, HG; Pala, EE; Ulkumen, BA; 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.
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    Oxytocin mitigates peripheral nerve damage via Nrf2 and irisin pathway
    Tosyali, HK; Bora, ES; Cinaroglu, OS; Erbas, O
    OBJECTIVE: Peripheral nerve injuries present challenges in achieving full functional restoration, necessitating effective therapeutic strategies. Oxytocin, known for its neuroprotective and anti-inflammatory properties, has shown potential in nerve recovery. This study aims to elucidate the role of oxytocin in nerve recovery via the nuclear factor erythroid 2-related factor 2 (Nrf2) and irisin pathways. MATERIALS AND METHODS: Adult male Wistar rats (n=30) were subjected to surgical dissection of sciatic nerves and divided into Control, Surgery and Saline Group, and Surgery and Oxytocin (OT) group. Electromyographic (EMG) recordings, inclined plane tests, and histological assessments were conducted to evaluate nerve function, and Nerve growth factor (NGF) immuno expression and axonal parameters were measured. Plasma irisin levels, nerve NGF, and Nrf2 levels were quantified. RESULTS: The Surgery and Saline Group exhibited impaired EMG latency, amplitude, and inclined plane score compared to Controls, while the Surgery and OT Group demonstrated improved outcomes. Histomorphometric analysis revealed increased NGF immunoexpression, axon number, diameter, and reduced fibrosis in the Surgery and OT Group. Plasma irisin levels were higher following oxytocin administration. Additionally, nerve NGF and Nrf2 levels were elevated in the Surgery and OT Group. CONCLUSIONS: OT administration mitigated nerve injury effects, promoting functional and histological improvements. Elevated NGF and Nrf2 levels, along with increased irisin, indicated the potential interplay of these pathways in enhancing nerve recovery. The results align with OT's neuroprotective and anti-inflammatory roles, suggesting its potential as a therapeutic intervention for nerve injuries. OT's positive impact on nerve recovery is associated with its modulation of Nrf2 and irisin pathways, which collectively enhance antioxidant defense and neurotrophic support and mitigate inflammation. These findings underline OT's potential as a therapeutic agent to enhance nerve regeneration and recovery. Further research is needed to elucidate the intricate molecular mechanisms and potential clinical applications of OT in nerve injury management.
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    Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model
    Oltulu, F; Aktug, H; Uysal, A; Turgan, N; Oktem, G; Erbas, O; Yavasoglu, NUK; Yavasoglu, A
    In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3,5-triiodo-l-thyronine (50 mu g/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.
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    Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats
    Artunc-Ulkumen, B; Pala, HG; Pala, EE; Yavasoglu, A; Yigitturk, G; Erbas, O
    We aimed to evaluate: (1) endometrial and ovarian tissue injury caused by the glucose toxicity in diabetic rat model and (2) the effect of GLP-1 analog (exenatide) on endometrial and ovarian diabetes induced injury with emphasizing the underlying mechanism. The study group composed of 24 female rats assigned randomly into 3 groups. Group 1 was the control group (n = 8) and received no treatment. Diabetes was induced by intraperitoneal injection of streptozocin for 16 rats which are further assigned randomly into 2 groups: 1 ml/kg intraperitoneal saline was given to Group-2 (diabetic non-treated control group, 8 rats) and 10 mu g/kg/day of intraperitoneal exenatide was given to Group 3 (exenatide treated group, 8 rats) for four weeks. After four weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Diabetes caused endometrial and ovarian tissue injury in rats (p < 0.0001). Serum transforming growth factor beta (TGF-beta), malonylaldehyde (MDA), pentraxin-3 (PTX-3) levels were higher in diabetic rats (p < 0.0001), whereas antimullerian hormone (AMH) was lower (p < 0.001). Serum levels of these markers reflected that Diabetes induced injury in the reproductive tract occured via oxidative stress, fibrosis and severe inflammation. Diabetes diminished ovarian reserve. Exenatide treatment improved the histological degeneration and fibrosis in the endometrium and ovary with concomitant decrease in inflammatory and oxidative stress markers (p < 0.05). Exenatide also improved ovarian reserve (p < 0.05). Glucose toxicity occured severely in ovary and endometrium in DM. After exenatide treatment; ovarian and endometrial injury and fibrosis seems to decrease significantly. The effects of exenatide in rat models give hope to prevent the women with DM from premature ovarian failure and endometrial dysfunction.
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    The Protective Effect of Losartan on Diabetic Neuropathy in a Diabetic Rat Model
    Cavusoglu, T; Karadeniz, T; Cagiltay, E; Karadeniz, M; Yigitturk, G; Acikgoz, E; Uyanikgil, Y; Ates, U; Tuglu, MI; Erbas, O
    Aim: Involvement of the peripheral and autonomic nervous systems is possibly the most frequent complication of diabetes. Important risk factors included hyperglycemia, dyslipidemia, hypertension, and smoking. Angiotensin-converting-enzyme inhibitor (ACE) inhibitors should be beneficial in all vascular beds, including neuropathy and retinopathy. In this study we aimed to evaluate the effect of the angiotensin receptor blocker losartan on diabetic neuropathy in a diabetic rat model. Material and Methods: 24 male, Sprague Dawley albino mature rats were divided into 3 groups; (1) control group: No drug was administered to the remainder of rats which blood glucose levels were under 120mg/dl, (2) diabetic control: rats were given no medication, but 4ml per day of tap water was given by oral gavage, (3) losartan groups: rats were given 10mg/kg/day oral of losartan for 4 weeks. Electromyography (EMG) was applied to anesthetized rats at the end of 4(th) weekend. Then, the animals were euthanized and sciatic nerve was performed for histopathological examination. Results: Compound Muscle Action Potential (CMAP) amplitude of diabetic rats receiving the Saline in the EMG was significantly reduced when compared to the control group. Distal latency value and CMAP duration of diabetic rats receiving the saline were meaningfully increased when compared to the control group. CMAP amplitude and CMAP duration of diabetic rats receiving the Losartan treatment in the EMG were meaningfully reduced when compared to diabetic rats receiving the Saline. Perineural thickness in the rats receiving the Losartan treatment was found to be significantly reduced when compared to the group receiving the Saline. Conclusions: As a result, it has been shown in this study that perineural thickness of the Losartan treatment was significantly reduced when compared to saline receiving group, significantly increased the immunoexpression of NGF, and also provided a significantly recovery in EMG when compared to Saline receiving group.
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    The effects of sunitinib on endometriosis
    Pala, HG; Erbas, O; Pala, EE; Ulkumen, BA; Akman, L; Akman, T; Oltulu, F; Yavasoglu, A
    The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student's t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.