Person: AKAKIN, DİLEK
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AKAKIN
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DİLEK
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Publication Open Access Ethanol extract of Cotinus coggygria leaves accelerates wound healing process in diabetic rats(TAYLOR & FRANCIS LTD, 2016-11) ŞEN, ALİ; Aksoy, Halil; Sen, Ali; Sancar, Mesut; Sekerler, Turgut; Akakin, Dilek; Bitis, Leyla; Uras, Fikriye; Kultur, Sukran; Izzettin, Fikret VehbiContext:Cotinus coggygria Scop. (Anacardiaceae) leaves that were used as wound healing in traditional Balkan and Anatolian folk medicine, could be potentially effective in treating diabetic wounds.Objective: This study investigates biochemical and histological effects of ethanol extract of C. coggygria (CCE) on excision wound model in diabetic rats.Materials and methods: This study was conducted on diabetic Wistar albino rats, which were injected by a single dose (50mg/kg i.p.) streptozotocin. Afterward an excision wound model was created in all animals; diabetic control rats were applied topically simple ointment and diabetic treatment rats were applied topically 5% (w/w) ointment with CC, once a day during the experimental period. Malondialdehyde, glutathione and hydroxyproline levels in wound tissues were investigated at the end of 3rd, 7th, and 14th days. Histopathological examination was also performed.Results: Hydroxyproline content was significantly increased in the CCE treated group versus control after the 3rd and 7th days (15.33 versus 11.83; 19.67 versus 15.67mg/g, p<0.05; respectively). A statistically significant elevation in glutathione at the end of 3rd, 7th, and 14th days (5.13 versus 1.58, p<0.05; 4.72 versus 1.88, p<0.05; 3.83 versus 1.88mol/g, p<0.05, respectively) and a statistically significant decrease in malondialdehyde level at the end of 7th day (4.49 versus 1.48nmol/g, p<0.05) were determined in the treated group versus control group. These results were also supported by histological analyses.Discussion and conclusion: These findings indicate that CCE accelerated the cutaneous wound healing process in diabetic wounds, in confirmation of its traditional use.Publication Open Access The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits(2022-11-01) AKAKIN, DİLEK; GÖREN, MEHMET ZAFER; Tekin N., Karamahmutoğlu T. E. , Aykaç A., AKAKIN D., GÖREN M. Z.© 2022Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates the behavioral and neurochemical effects of JP-1302, a selective α2C-adrenoceptor antagonist, in a model of schizophrenia-like deficits induced by sub-chronic ketamine (KET) administration. Here, we administered ketamine (25 mg/kg, i.p.) to male and female Wistar rats for eight consecutive days. On the last two days of ketamine administration, rats were pretreated with either JP-1302 (1-3-10 μmol/kg, i.p.), chlorpromazine (0.1 mg/kg, i.p.), or saline, and the behavioral tests were performed. Behaviors related to positive (locomotor activity), negative (social interaction), and cognitive (novel object recognition) symptoms of schizophrenia were assessed. Glutamate, glutamine, GABA levels, and α2C-adrenoceptor expression were measured in the frontal cortex and the hippocampus. Tyrosine hydroxylase immunocytochemical reactivity was also shown in the midbrain regions. Sub-chronic ketamine administration increased locomotor activity and produced robust social interaction and object recognition deficits, and JP-1302 significantly ameliorated ketamine-induced cognitive deficits. Ketamine induced a hyperdopaminergic activity in the striatum, which was reversed by the treatment with JP-1302. Also, the α2C-adrenoceptor expression was higher in the frontal cortex and hippocampus in the ketamine-treated rats. Our findings confirm that α2C-adrenoceptor antagonism may be a potential drug target for treating cognitive disorders related to schizophrenia.Publication Open Access Effects of montelukast sodium on tendon healing: An experimental study(SPRINGER HEIDELBERG, 2013) AKAKIN, DİLEK; Polat, Atilla; Canbora, Mehmet Kerem; Akakin, Dilek; Aykanat, FarukIntroduction: Montelukast sodium (MS) a selective leukotriene antagonist of the cysteinyl leukotriene receptor, has been used in the treatment of asthma and allergic rhinitis. In this study, we evaluated the effect of MS on the early inflammatory phase (histological) of nonsynovial tendon healing. Materials and Methods: Rats were divided randomly into two groups (n = 6 each). MS (Singulair) was administered to one group at 10 mg/kg/day [250 g/day intraperitoneally (i.p.)]. The control group was administered 250 g/day of 0.9% saline i.p. This nonsynovial tendon was longitudinally divided at the midportion, cut transversely and then sutured. In both groups, the rats were sacrificed by decapitation 10 days later. Results: Decreased inflammatory cell infiltration and more properly oriented collagen fibres were observed in the MS group's histopathological specimens as compared to the control group's (P < 0.05). Additionally, vascularity was decreased in the MS group. Conclusion: MS decreased tendon healing, apparently by inhibiting the early inflammatory phase of nonsynovial tendon healing.Publication Open Access Electron microscopic GABA evaluation in hippocampal mossy terminals of genetic absence epilepsy rats receiving kindling stimulations(2022-12-01) KAYA, ÖZLEM TUĞÇE; TURGAN AŞIK, ZEHRA NUR; KARAMAHMUTOĞLU, TUĞBA; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; AKAKIN, DİLEK; ŞİRVANCI, SERAP; İmdat N. N., KAYA Ö. T., TURGAN AŞIK Z. N., ERYİĞİT KARAMAHMUTOĞLU T., GÜLÇEBİ İDRİZ OĞLU M., AKAKIN D., ONAT F., ŞİRVANCI S.Objective: The hypotheses related to the fact of epileptic mechanisms are mainly based on excitation-inhibition imbalance in central nervous system. GAERS (Genetic Absence Epilepsy Rats from Strasbourg) is a well-known animal model of absence epilepsy, and frequently used in experimental studies. In the present study, we aimed to examine possible morphological and gamma-aminobutyric acid (GABA) density changes in GAERS hippocampus after electrical kindling stimulations. Methods: All control and test group rats received 6 kindling stimulations. Rats were decapitated 1 h after the last stimulation. Ultrastructural GABA immunocytochemistry was used to evaluate GABA density quantitatively in mossy terminals of hippocampal CA3 region. Results: GABA levels were less in kindling groups compared to their controls, and in GAERS groups compared to Wistar groups; mitochondrial and dendritic spine area ratios were greater in GAERS groups compared to Wistar groups, although all these evaluations were statistically nonsignificant. Depletion of synaptic vesicles was evident in the mossy terminals of kindling groups. Conclusion: The reason of decreased levels of GABA found in the present study might be that GABA has been released from the synaptic pool rapidly at an early time period after the last stimulation, for compansation mechanisms. Depletion of synaptic vesicles observed in kindling groups shows that even 6 kindling stimulations have an impact of changing hippocampal morphology in trisynaptic cycle. The increased mitochondrial area in GAERS might be related to the increased mitochondrial activity. The increased dendritic spine area might be related to the increased performance of learning in GAERS. Our findings indicating that absence epilepsy and temporal lobe epilepsy have different mechanisms of epileptogenesis might be a basis for further experimental studies.Publication Open Access The Effect of Algan Hemostatic Agent (AHA) on Wound Healing(MARMARA UNIV, INST HEALTH SCIENCES, 2020-09-04) ŞEN, ALİ; Aksoy, Halil; Sener, Azize; Akakin, Dilek; Sen, Ali; Ozakpinar, Ozlem Bingol; Ozcan, Sinemcan; Simsek, Ahmet Kaan; Sekerler, Turgut; Guzel, Sevket Ergun; Midi, AhmetObjective: The Algan Hemostatic Agent (AHA) is a novel herbal originated blood stopper. The aim of this study is to investigate the effect of AHA on wound healing on excisional wound model in rats. Methods: In this study, 54 adult Wistar albino rats were used. Rats were divided into 3 groups (saline, Madecassol (R) and AHA). Each group was then divided into 3 subgroups as the 3rd, 7th and 14th days. Two wounds were created in the dorsal thoracic region of the rats. One of the lesions was used for histopathological examinations and the other for hydroxyproline measurement. In order to evaluate the wound healing, wound area were measured during the whole treatment period and animals were sacrificed at the end of the 3rd, 7th and 14th days and tissue samples were taken for the determination of hydroxyproline levels. Results: AHA treatment did not cause significant difference in hydroxyproline level on days 3, 7, 14. The contraction percentage of wound area was higher in the AHA group on day 7 than that of the control group. However, the difference was not statistically significant (p>0.05). On days 3 and 14, no significant difference was detected in the contraction percentage of wound area between the control and the AHA groups. AHA and Madecassol (R) results of epidermis regeneration on the 14th day, neutrophil infiltration on the 7th day and edema on the 3rd, 7th and 14th days were different in terms of histopathological parameters compared to the control group. Conclusion: Despite good histological findings, AHA did not significantly accelerate wound healing, but did not adversely affect wound healing as well.Publication Open Access Effects of sodium fluoride on neural tube development in chick embryos(2023-11-01) AKAKIN, DİLEK; Mammadov M., Emon S. T., Akar E., AKAKIN D., Şener D.Objective: Various environmental factors encountered in daily life are associated with the development of neural tube defects. This study aims to investigate the effects of fluoride on neural tube development in chick embryos. Methods: A total of 60 specific pathogen-free, fertile, zero-day Leghorn-type eggs were used in the study. Group 1 was the control group, in which only saline was administered. Group 2 was the low-dose group, in which 0.003 mg of fluoride was administered, and Group 3 was the high-dose group, in which 0.006 mg of fluoride was administered. After 72 h of incubation, the embryonic disc was evaluated microscopically. Results: In the control group, the surface ectoderm of all sections was intact, the neural tube was closed, and the neuroepithelium, the basement membrane surrounding the neuroepithelium, the somites, and the notochord displayed standard structure. Neural tube defects were observed in 3 of the chick embryos, that was given low-dose fluoride. In Group 3, which was administered high doses of fluoride, neural tube defects were observed in 4 embryos. It was observed that the development of neural tube defects was no statistically significantly higher in low and high-dose fluoride group compared to the control group. Conclusion: Low and high-dose fluoride exposure was associated with developing neural tube defects, but there was no statisticaly significance.Publication Open Access Bilayered laponite/alginate-poly(acrylamide) composite hydrogel for osteochondral injuries enhances macrophage polarization: An in vivo study(2022-03-01) AKAKIN, DİLEK; GÜNEŞ, KASIM; ALARÇİN, EMİNE; Saygili E., Saglam-Metiner P., Cakmak B., ALARÇİN E., Beceren G., Tulum P., Kim Y., GÜNEŞ K., Eren-Ozcan G. G., AKAKIN D., et al.Addressing osteochondral defects, the objective of current study was to synthesize bilayered hydrogel, where the cartilage layer was formed by alginate (Alg) polyacrylamide (PAAm) with and without the addition of TGF-beta 3 and bone layer by laponite XLS/Alg-PAAm and characterize by in vitro and in vivo experiments. Exceeding the mechanical strength of Alg-PAAm (32.95 +/- 1.23 kPa) and XLS based (317.5 +/- 21.72 kPa) hydrogels, XLS/Alg-PAAm hydrogel (469.7 +/- 6.1 kPa) activated macrophages towards M2 phenotype and stimulated the expression of anti-inflammatory factors. The addition of TGF-beta 3 accelerated transition of macrophage polarization, especially between day 4 and 7. The expression levels of MI-related genes such as CD80, iNOS and TNF-alpha decreased gradually after day 4, reaching lowest values at day 13, whereas the expression levels of M2-related genes, CD206, Argi and SFAT6 significantly increased promoting M2 macrophage polarization, which might be associated with accelerated bone repair. Moreover, bilayer structure exhibited a better cell viability as well as rcpainnent thorough the XIS contents. in vivo histological examinations verified the significant surface regularity and hyaline like tissue formation employment, along with synchronized degradation profile of the hydrogel with tissue healing at the end of 12 weeks. A mechanically durable, biocompatible and immunocompatiblc hydmgcl was formulated to be utilized in bone-cartilage engineering applications.Publication Open Access Duration of ciprofloxacin use is important in the development of abdominal aortic aneurysm in a rat model(2022-11-01) ÖZYILMAZ YAY, NAGEHAN; ERGELEN, RABİA; AKAKIN, DİLEK; GÜLHAN, REZZAN; Çulpan Y., Keçeci İ., Sandıkçı İ., Gökçe Ş., Göker H., ÖZYILMAZ YAY N., ERGELEN R., AKAKIN D., GÜLHAN R.BACKGROUND: Recent findings suggest that fluoroquinolones, most prescribed antibiotic to treat various infections, have increased abdominal aortic aneurysm formation. We aimed to investigate the relation of the development of abdominal aortic aneurysm and the duration of ciprofloxacin use. METHODS: Male Sprague-Dawley rats were divided into 2 groups to administer saline to the control groups and CaCl2 to the aneurysm groups. These groups were then divided into 3 subgroups: intraperitoneal saline, ciprofloxacin for 2 weeks, and ciprofloxacin for 4 weeks. At the end of 4 weeks, the diameter of abdominal aorta was determined by ultrasonography and animals were sacrificed to obtain abdominal aorta specimens. Elastic fiber fracture, tunica media layer thickness, and aortic tissue damage were evaluated histologically. RESULTS: Aortic diameter of control-saline (2.15 mm ± 0.06), control-2 weeks (2.25 mm ± 0.06), and control-4 weeks (3.31 mm ± 0.09) ciprofloxacin groups was significantly different (P .05). CONCLUSION: The study showed that ciprofloxacin caused injury in the aortic wall but not a significant change in the thickness of the aortic tunica media layer. The duration of ciprofloxacin use was important in the development of aneurysm and aneurysm severity.Publication Open Access Myrtus communis L. Extract Ameliorates High Fat Diet Induced Kidney and Bladder Damage by Inhibiting Oxidative Stress and Inflammation(2022-12-02) ERTAŞ, BÜŞRA; ŞEN, ALİ; AKAKIN, DİLEK; ERCAN, FERİHA; Kanpalta Mustafaoğlu F., Ertaş B., Şen A., Akakın D., Şener G., Ercan F.Objective: Obesity is associated with many diseases, including urinary system disorders such as chronic kidney disease and overactive bladder syndrome. Myrtus communis L. (MC) extract has been reported to have antioxidant and anti-inflammatory effects. The aim of this study was to investigate the protective effects of MC extract on high-fat diet (HFD)-induced kidney and bladder damage. Materials and Methods: Wistar albino male rats were divided into three experimental groups: control, HFD and HFD+MC. Experimental groups were fed a standard diet (control group) or HFD (HFD and HFD+MC groups) for 16 weeks. MC extract (100 mg/kg) was administered to the HFD+MC group orally during the last 4 weeks (5 days/week) of the experiment. Highdensity lipoprotein, total cholesterol, triglyceride and leptin levels were measured in blood serum. Tissue malondialdehyde (MDA), glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and myeloperoxidase (MPO) levels were evaluated biochemically. Kidney and bladder morphology, NADPH oxidase-2 (NOX-2) and nuclear factor-kappa B (NF-ҡB)-positive and apoptotic cells were evaluated histologically. Results: Lipid profiles altered and leptin levels increased in blood serum. MDA, 8-OHdG and MPO levels increased and GSH level decreased in kidney and bladder in the HFD group. Moreover, degenerated kidney and bladder morphology, increased NOX-2 and NF-ҡB-positive and apoptotic cells were observed in this group. All of these biochemical and histological parameters were ameliorated in the HFD+MC group. Conclusion: HFD-induced obesity causes kidney and bladder damage by oxidative and inflammatory processes. MC extract may reduce oxidative stress and inflammation and play a protective role in obesity-related kidney and bladder damage.Publication Open Access Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study(ROYAL SOC, 2020-01) AKAKIN, DİLEK; Cam, Muhammet Emin; Yildiz, Sila; Alenezi, Hussain; Cesur, Sumeyye; Ozcan, Gul Sinemcan; Erdemir, Gokce; Edirisinghe, Ursula; Akakin, Dilek; Kuruca, Durdane Serap; Kabasakal, Levent; Gunduz, Oguzhan; Edirisinghe, MohanIn order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-gamma agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.