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Öğe A Phosphodiesterase Type-5 (PDE-5) Inhibitor, Sildenafil, Ameliorates the NEC Induced Inflammation(Springer, 2025) Ovali, Mehmet Akif; Oztopuz, Ozlem; Karaboga, IhsanThe connection between intestine microbiota and lung disease is described as the gut-lung axis, these organ systems are somehow interrelated in both homeostasis and disease development. In newborns, the most important gastrointestinal complications are necrotizing enterocolitis (NEC), and the pulmonary complication both cause significant systemic morbidity. In this study, sildenafil administered at varying doses in neonatal rat model of experimental necrotizing enterocolitis and focused on both mRNA expression and histopathological alterations. 15-day-old Wistar Albino rat pups were randomly divided into six groups; Control, NEC, DMSO, Sil_1mg, Sil_5mg, Sil_10mg (n = 5). NEC induction was performed using hypoxia/asphyxia and cold stress. At the end of the experiment, lung tissues were harvested, molecular and histopathological alterations were analysed. Histopathological examination was performed with hematoxylin&eosin and masson trichrome staining in lung samples of neonatal rats and the mRNA expression levels of TNF-alpha, IL-6 and HSPa5 genes were analyzed. The mRNA expression levels of TNF-alpha, IL-6 and HSPa5 were increased in the NEC group compared to the control group and sildenafil treatment could significantly reduced the levels of the genes and inflammation (*p < 0.05 and **p <= 0.0001). Alveolar edema and hemorrhage findings were observed in the lung tissue of the NEC group. Interstitial edema and hemorrhage findings were reduced in the groups treated with sildenafil compared to the NEC group. The data we obtained indicate that sildenafil administering at different doses has therapeutic effect on NEC induced lung tissue inflammation both at the mRNA expression and tissue levels.Öğe Asprosin, a C-Terminal Cleavage Product of Fibrillin 1 Encoded by the FBN1 Gene, in Health and Disease(Karger, 2022) Ovali, Mehmet Akif; Bozgeyik, IbrahimBackground: Asprosin is a novel fasting-induced, glucogenic, and orexigenic protein hormone that is discovered with the help of genetic studies in patients with neonatal progeroid syndrome. Asprosin is encoded by the penultimate 2 exons (65 and 66) of the fibrillin 1 (FBN1) gene. Profibrillin 1 is the unprocessed protein product of FBN1 and undergoes a proteolytic cleavage by furin enzyme to produce mature fibrillin 1 and asprosin. The main organ responsible for the asprosin production seems to be white adipose tissue. Summary: Asprosin promotes hepatic glucose release in the liver and appetite stimulation in the hypothalamus through activation of the cAMP signaling circuitry through interacting with its G protein-coupled receptor, called OR4M1. Increasing mass of evidence suggests that asprosin is involved in the development and progression of various clinical conditions including diabetes, obesity, cardiomyopathy, cancer, and polycystic ovarian syndrome. It regulates various cellular and physiological processes such as appetite stimulation, glucose release, insulin secretion, apoptotic cell death, and inflammatory response. In this review, we discuss the current literature on asprosin and try to shed light on the yet undiscovered functions of asprosin. Key Message: Asprosin is a key regulatory factor for preserving the homeostasis of energy metabolism.Öğe Comparison of the effects of various airway devices on hemodynamic response and QTc interval in rabbits under general anesthesia(Springer Heidelberg, 2015) Toman, Huseyin; Erbas, Mesut; Sahin, Hasan; Kiraz, Hasan Ali; Uzun, Metehan; Ovali, Mehmet AkifIn this study, we aimed to compare the effects of various airway devices on QTc interval in rabbits under general anesthesia. The subjects were randomly separated into four groups: Group ETT, Group LMA, Group PLA, Group V-gel. Baseline values and hearth rate, mean arterial pressure and ECG was obtained at the 1st, 5th and 30th minutes after administration of anesthesia and placement of airway device and, QTc interval was evaluated. Difference was observed between ET group and V-gel group in the 5th minute mean arterial pressure values (p < 0.05). It was observed that QTc intervals at the 1st and 5th minute in the ET group significantly increased when compared with the other groups (p < 0.05). Again, it was observed that QTc interval of ET group at the 15th and 30th minute was longer when compared with PLA and V-gel groups (p < 0.05). It was also observed that QTc interval of LMA Group at the 5th minute after intubation significantly increased when compared with V-gel group (p < 0.05). It was observed that HR values of ETT group at the 1st, 5th and 15th minutes after intubation increased with regards to PLA and V-gel groups (p < 0.05). It was determined that the 30th minute hearth rate of ETT group was higher when compared to V-gel group (p < 0.05). Conclusion: In our study we observed that V-gel Rabbit affected both hemodynamic response and QT interval less than other airway devices.Öğe Effects of Melatonin on Blood Pressure, Oxidative Stress and Placental Expressions of TNF?, IL-6, VEGF and sFlt-1 in RUPP Rat Model of Preeclampsia(Elsevier Science Inc, 2017) Uzun, Metehan; Gencer, Meryem; Turkon, Hakan; Oztopuz, Rahime Ozlem; Demir, Ufuk; Ovali, Mehmet Akif[Anstract Not Available]Öğe Effects of Melatonin on Cardiac Ion Channels in Rats with Metabolic Syndrome(Wiley, 2022) Ovali, Mehmet Akif; Oztopuz, Ozlem; Vardar, Selma Arzu[Anstract Not Available]Öğe Humic Acid Has Protective Effect on Gastric Ulcer by Alleviating Inflammation in Rats(Pleiades Publishing Inc, 2022) Sehitoglu, Muserref Hilal; Oztopuz, Ozlem; Karaboga, Ihsan; Ovali, Mehmet Akif; Uzun, MetehanThe new agents are needed in treatment of gastric ulcer that have less side effects, adequate efficacy, and no drug interactions. In this study, we aimed to investigate the potential protective effects of humic acid on experimental gastric ulcer. Wistar Albino male rats (n = 48) were randomly divided into 8 groups as follow; Control (without any applications), Humic acid (50 mg/kg), ethanol group (1 mL/rat), and indomethacin group (25 mg/kg). In the treatment groups, both gastric ulcer model and humic acid 50 mg/kg were applied. In addition, famotidine the antiulcer drug was used as positive control. All medications were administered by oral gavage. Levels of ADAM10 and ADAMTS12 in gastric mucosa were determined by ELISA method. Hematoxylin-Eosin (H&E) staining, iNOS, and PCNA immunohistochemical staining were performed for histopathological investigations. Apoptosis was demonstrated by using the TUNEL method. In addition, the levels of inflammatory cytokines (TNF-alpha, IL-6, IL-10) and caspase-3 gene were determined by qRT-PCR. ADAM10 and ADAMTS12 levels significantly increased in the treatment groups compared to the ulcer groups (p < 0.05). The experimental groups showed mucosal erosion, bleeding, leukocyte infiltration and edema. Treatment with humic acid and famotidine was found to suppress iNOS activity, thereby decreasing proinflammatory activity and preventing damage to the gastric mucosa, while reducing the number of apoptotic cells. IL-6, IL-10, TNF-alpha and caspase-3 levels were significantly decreased in the treatment groups compared to damaged gastric mucosa. As a result, humic acid may be defined as a potential protective agent with its anti-inflammatory effect in gastric ulcer.Öğe Hyperbaric oxygen treatment ameliorates gentamicin-induced nephrotoxicity and expression of kidney injury molecule 1 in the rat model(Undersea & Hyperbaric Medical Soc Inc, 2019) Oztopuz, Ozlem; Turkon, Hakan; Sehitoglu, Muserref Hilal; Buyuk, Basak; Uzun, Metehan; Ovali, Mehmet Akif; Demir, UfukIn recent years, hyperbaric oxygen (HBO2) therapy has been considered as an effective method for the treatment of gentamicin (GM)-induced renal toxicity. However, the findings related to the use of HBO2 for GM toxicity are limited and contradictory. The aim of this study is to investigate the protective role of HBO2 on GM-induced nephrotoxicity. For this purpose, Wistar albino rats (n=28) were randomly divided into four equal groups: C, HBO2, GM and GM+HBO2. GM (100 mg/kg, ip) and HBO2 were applied over seven days. On the eighth day blood and kidney tissue samples were harvested. The albumin, creatinine, and urea levels were determined from serum samples. Superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) activities, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) values were analyzed spectrophotometrically. The relative expression level of TNF-alpha, IL-1 beta and Kim-1 gene were determined by qRT-PCR assays; histopathologic investigation was completed in kidney tissue samples. Serum urea, albumin and creatinine levels significantly increased in the GM group compared to the GM+HBO2 group. For antioxidant parameters the GM+HBO2 group was not statistically different from the C group but was significantly different compared with the GM group. TNF-alpha, IL-1 beta and Kim-1 gene expression levels in the GM group were statistically increased compared to the GM+HBO2 group (p=0.015, p=0.024, p=0.004) respectively. Severe tubular necrosis, epithelial desquamation and mild peritubular hemorrhage were observed in the GM-administrated group, while HBO2 exposure ameliorated these alterations. In conclusion, HBO2 exposure may be defined as a potential method for the prevention of GM-induced renal toxicity.Öğe Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats(Springer, 2020) Oztopuz, Ozlem; Turkon, Hakan; Buyuk, Basak; Coskun, Ozlem; Sehitoglu, Muserref Hilal; Ovali, Mehmet Akif; Uzun, MetehanValproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Therefore, the present study designed to investigate the probable protective role of melatonin against VPA-induced liver toxicity. For that purpose, 28 Wistar rats were randomly selected and divided into four groups, namely the Group C (vehicle), VPA (500 mg/kg/day VPA), MEL + VPA (10 mg/kg/day melatonin + 500 mg/kg/day VPA) and MEL (10 mg/kg/day melatonin). The agents were given by oral gavage for 14 days. Blood and liver tissue samples from all the rats were harvested on the 15th day of experiment. Biochemical analyses were conducted on the blood samples. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), alpha glutathione S-transferases (alpha-GST), nuclear factor-kappa B (NF-kappa B), myeloperoxidase (MPO) and changes in gene expression were examined in the liver tissues. Also, liver histopathological analyses were conducted. VPA administration significantly increased the levels of alpha-GST, MDA, NF-kappa B and of IL-1 beta, TNF-alpha gene expression in the liver compared to Group C. Moreover, vacuolization, hydropic degeneration, inflammatory cell infiltration, and sinusoidal congestion were commonly detected in the VPA-treated group along with the highest apoptotic index (TUNEL staining) values. Melatonin administration was revealed to exhibit powerful protective properties at cellular, inflammatory and oxidative level activities against VPA-induced liver toxicity. Therefore, melatonin administration may be used as an adjuvant therapy against to VPA-induced liver toxicity.Öğe Melatonin attenuates caspase-dependent apoptosis in the thoracic aorta by regulating element balance and oxidative stress in pinealectomised rats(Canadian Science Publishing, 2019) Doganlar, Zeynep Banu; Uzun, Metehan; Ovali, Mehmet Akif; Dogan, Ayten; Ongoren, Gulin; Doganlar, OguzhanThe aim of this study was to explain the possible mechanisms by which melatonin deficiency results in cardiovascular injury and to investigate the effects of melatonin administration on important signalling pathways and element equilibrium in the thoracic aorta (TA). For this purpose, we analysed the cellular and molecular effects of melatonin deficiency or administration on oxidative stress, DNA damage, molecular chaperone response, and apoptosis induction in TA tissues of pinealectomised rats using ELISA, RAPD, qRT-PCR, and Western blot assays. The results showed that melatonin deficiency led to an imbalance in essential element levels, unfolded or misfolded proteins, increased lipid peroxidation, and selectively induced caspasedependent apoptosis in TA tissues without significantly affecting the Bcl-2/BAX ratio (2.28 in pinealectomised rats, 2.73 in pinealectomised rats treated with melatonin). In pinealectomised rats, the genomic template stability (80.22%) was disrupted by the significantly increased oxidative stress, and heat shock protein 70 (20.96-fold), TNF-alpha (1.73-fold), caspase-8 (2.03-fold), and caspase-3 (2.87-fold) were markedly overexpressed compared with the sham group. Melatonin treatment was protective against apoptosis and inhibited oxidative damage. In addition, melatonin increased the survivin level and improved the regulation of element equilibrium in TA tissues. The results of the study indicate that melatonin deficiency induces TNF-alpha-related extrinsic apoptosis signals and that the administration of pharmacological doses of melatonin attenuates cardiovascular toxicity by regulating the increase in the rate of apoptosis caused by melatonin deficiency in TA tissue of Sprague-Dawley rats.Öğe Melatonin Improves Left Ventricular Mitochondrial Dynamics in Rats(Pleiades Publishing Inc, 2022) Uzun, Metehan; Oztopuz, Ozlem; Eroglu, Huseyin Avni; Doganlar, Oguzhan; Doganlar, Zeynep Banu; Ovali, Mehmet Akif; Demir, UfukThere is increasing awareness that efficient and regular mitochondrial dynamics improvement cardiac function and affects the quality of life. Melatonin is a main pineal gland hormones and ameliorates mitochondrial dynamics in many cardiac disorders. For that purpose, we administrated melatonin to healthy rats all day long in order to investigate change in left ventricle mitochondrial dynamics both in the end of the nighttime and daytime. Twenty male Wistar rats (3-4 months age) were randomly assigned into Control (C; n = 10) and Melatonin groups (MEL; 10 mg/kg melatonin added drinking water, n = 10). On the 5th day of the study, 5 rats from the groups were randomly selected and euthanized at 08:00 AM and the remaining 5 rats were euthanized at 20:00 PM from each groups and samples of left ventricle (LV) tissue were harvested. Quantitative real-time PCR and western blot analysis demonstrated that melatonin acts preventive role on mitochondrial fusion and mitophagy through the DRP1/FIS1 and BNIP3/NIX axis, respectively. Additionally, melatonin administration significantly reduced P21 activation, induced cell cycle arrest, P27, finally regulated caspase-depended mitochondrial apoptosis signals in a time dependent manner. Our results suggest that melatonin may emerge as a therapeutic candidate to protect the bioenergetic dynamics of mitochondria in hearth.Öğe Melatonin regulates oxidative stress and apoptosis in fetal hearts of pinealectomised RUPP rats(Taylor & Francis Inc, 2020) Doganlar, Oguzhan; Doganlar, Zeynep Banu; Ovali, Mehmet Akif; Guclu, Orkut; Demir, Ufuk; Dogan, Ayten; Uzun, MetehanObjective This study aimed to investigate the effects of melatonin on cardiac oxidative stress and apoptosis in the fetal heart in RUPP rats. Methods The fetal heart samples were obtained from melatonin administrated RUPP rats Results Our results indicate that preeclampsia exacerbated by melatonin deficiency triggers hypoxic conditions, both mis/un-folded protein response, oxidative stress-induced DNA damage and apoptosis. Melatonin treatment provided significant therapeutic effects on fetal hearts via regulating all these stress response at cellular and molecular levels. Conclusion Melatonin may be considered as a potential molecule for development of preventive strategies to reduce the PE induced risk of cardiovascular diseases in offspring.Öğe Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage (Mar, 10.1007/s12035-023-03306-x, 2023)(Springer, 2023) Akar, Ali; Oztopuz, Rahime Ozlem; Buyuk, Basak; Ovali, Mehmet Akif; Aykora, Damla; Malcok, Umit Ali[Anstract Not Available]Öğe Potential Biomarkers for Melatonin Deficiency in Thoracic Aorta and Left Ventricle of Pinealectomised Rats(Wiley-Blackwell, 2015) Doganlar, Oguzhan; Uzun, Metehan; Doganlar, Zeynep Banu; Ovali, Mehmet Akif; Ongoren, Gulin[Anstract Not Available]Öğe Role of Exogenous and Endogenous Melatonin in REM Sleep Retriction-Induced Pain Model(Wiley, 2023) Gunduz, Samime Sarli; Ozturk, Levent; Kaya, Oktay; Ovali, Mehmet Akif[Anstract Not Available]Öğe Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model(Springer, 2020) Duran, Yasin; Karaboga, Ihsan; Polat, Fatin Rustu; Polat, Elif; Erboga, Zeynep Fidanol; Ovali, Mehmet Akif; Oztopuz, Rahime OzlemThe aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1 ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-kappa beta) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin - 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) genes in gastric tissues was determined by real-time PCR; and TNF-alpha, IL-10, and IL-1 beta levels were determined. RJ was found to inhibit iNOS and Nf-kappa beta activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-alpha and IL-1 beta levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model.Öğe Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model (vol 47, pg 8867, 2020)(Springer, 2024) Duran, Yasin; Karaboga, Ihsan; Polat, Fatin Rustu; Polat, Elif; Erboga, Zeynep Fidanol; Ovali, Mehmet Akif; Oztopuz, Rahime Ozlem[Anstract Not Available]Öğe The Effects of Melatonin on Blood Pressure, Oxidative Stress and Expression Levels of Placental Tnf?, IL-6, VEGF and Sflt-1 Genes in RUPP Rat Model of Preeclampsia(Wiley, 2017) Uzun, Metehan; Oztopuz, Rahime Ozlem; Turkon, Hakan; Gencer, Meryem; Demir, Ufuk; Ovali, Mehmet Akif[Anstract Not Available]Öğe The Effects of Melatonin on Kcnq, Kcnh2 Gene Expression and QT Duration in Experimantally Hypertensive Male Rats(Wiley-Blackwell, 2015) Ovali, Mehmet Akif; Uzun, Metehan[Anstract Not Available]Öğe The investigation of airway management capacity of v-gel and cobra-PLA in anaesthetised rabbits(Acta Cirurgica Brasileira, 2015) Uzun, Metehan; Kiraz, Hasan Ali; Ovali, Mehmet Akif; Sahin, Hasan; Erbas, Mesut; Toman, HuseyinPURPOSE: To evaluate the applicability and airway management capacity of v-gel(R) and Cobra PLA in rabbit anaesthesia during assisted (AV) or controlled ventilation (CV). METHODS: This study was carried out in 44 adult New Zealand white rabbit. Baseline arterial pH, PaCO2 and PaO2 values were recorded. Anaesthesia was induced with 5 mg/kg xylasine and 35 mg/kg ketamine HCI combination. AV rabbits were assigned as; control (CG-AV; n=5), LMA (LMA-AV; n=5), cobra PLA (PLA-AV; n=5) and v-gel (v-gelAV; n=5). Rabbits have CV were also assigned as; ET (ET-CV; n=6), LMA (LMA-CV; n=6), cobraPLA (PLA-CV; n=6) and v-gel (v-gelCV; n=6). All measurements were repeated 1st, 5th, 15th and 30th mins during anaesthesia. RESULTS: The less insertion time, number of attempt and complications are recorded in v-gel applied rabbits compared to other apparatus. For arterial pH values significant differences are recorded in especially at 15th and 30th min between groups of CV (p<0.005 or p<0.001). All groups had similar results with each other during anaesthesia for PaCO2 except for LMA-CV group. CONCLUSION: The v-gel may be used as airway device in rabbit anaesthesia undergoing AV or CV and also can be a suitable alternative to endotracheal tubes and laryngeal mask airway.Öğe The Investigation of Melatonin and Remifentanyl Injection on Hemodynamic and Cardiac Parameters in Anaesthetised Rabbits(Wiley-Blackwell, 2015) Uzun, Metehan; Barutcu, Ahmet; Toman, Huseyin; Erbas, Mesut; Ovali, Mehmet Akif; Bekler, Adem[Anstract Not Available]
