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Öğe Effects of Cerebral Glucagon Administration on Blood Glucose Homeostasis in Rats(Wiley, 2023) Tanbek, Kevser; Yilmaz, Umit; Gul, Mehmet; Koc, Ahmet; Sandal, Suleyman[No abstract available]Öğe Effects of the genetic variants and serum levels of TIMP-1 and TIMP-2 on type 2 diabetes mellitus in the Turkish population(Bayrakol Medical Publisher, 2024) Celik, Faruk; Yilmaz, Umit; Yilmaz, Nesibe; Ozyavuz, Kerem; Basaran, Cem; Fazliogullari, Osman; Ergen, ArzuAim: Genetic and environmental factors are very important in the formation of type 2 diabetes mellitus (T2DM). Tissue inhibitors of matrix metalloproteinases (TIMPs) play central roles in inhibition of the extent of extracellular matrix degradation. The aim of this study is to investigate serum levels and gene polymorphisms of TIMP-1 and TIMP-2, and their effects on T2DM in the Turkish population. Material and Methods: One hundred seventeen patients with T2DM and 127 healthy controls were included in this study. TIMP-1 372 T>C, TIMP-2 303C>T, and TIMP-2 418 G>C polymorphisms were determined by PCR-RFLP method and serum TIMPs levels were measured by ELISA. Results: The frequencies of the TT genotype and T allele of the TIMP-2 303 C>T polymorphism were significantly higher in the patient group than in the control group. The frequency of the C allele for TIMP-2 418 G>C polymorphism was significantly higher in the control group than in patients. TIMP-1 372 T>C polymorphism was not statistically significant between patients and controls. Additionally, TIMP-1 serum levels were statistically higher in T2DM patients than in controls. Discussion: This study provides the first evidence that the TT genotype and T allele of the TIMP-2 303 C>T polymorphism significantly contribute to the risk of T2DM in the Turkish population. Also, carrying the C allele of the TIMP-2 418 G>C polymorphism had a protective effect against the development of T2DM. In addition, our results suggest that the C allele of the TIMP-1 372 T>C polymorphism may have protective effects against the development of T2DM.Öğe Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis(Wiley, 2024) Yilmaz, Umit; Tanbek, Kevser; Gul, Semir; Koc, Ahmet; Gul, Mehmet; Sandal, SuleymanHere, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.Öğe Intracerebroventricular prokineticin 2 infusion may play a role on the hypothalamus-pituitary-thyroid axis and energy metabolism(Pergamon-Elsevier Science Ltd, 2024) Yilmaz, Umit; Tanbek, KevserAim: The hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue. Material and Methods: A total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n=10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1 alpha and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR. Results: Icv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p<0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1 alpha UCP1 in the WAT and BAT (p<0.05). Conclusion: Icv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis.Öğe Investigation of the Effect of Astaxanthin on Autophagy in Renal Ischemia-reper fusion Modeled Rats(Galenos Publ House, 2024) Kisaoglu, Aysegul; Kose, Evren; Yilmaz, Nesibe; Tanbek, Kevser; Yildiz, Azibe; Yilmaz, Umit; Cirik, Rumeyza HilalObjective: The aim of this study was to investigate the effect of various astaxanthin (ATX) doses on oxidative damage and autophagy in renal ischemia-reperfusion (I/R) injury-modeled rats. Methods: The rats were divided into five groups: sham group (n=8), I/R (n=8), I/R + 5 mg/kg ATX (n=8), I/R + 10 mg/kg ATX (n=8), and I/R + 25 mg/ kg ATX (n=8) groups. ATX was dissolved in 5 mg/kg, 10 mg/kg, and 25 mg/ kg olive oil for 7 days and administered to the rats in the experimental group. Sham and I/R groups were also administered ATX solution (olive oil) via oral gavage for 7 days. Renal ischemia reperfusion was induced in all rats except the sham group after the last dose was administered on the 7 th day. Reperfusion was conducted for 24 hours after 45 minutes of ischemia. Results: Blood samples were collected, and kidney tissue were incised for biochemical and histological analyses. Superoxide dismutase (SOD) and total antioxidant status (TAS) were significantly lower in the I/R group than in the sham group (p<0.05), whereas malondialdehyde (MDA) and total oxidant status (TOS) values were higher (p<0.05). It was determined that SOD and TAS increased and MDA and TOS decreased in the ATXadministration groups compared with the I/R group, independent of the dose (p<0.05). In the 25 mg/kg ATX + I/R group, Beclin-1 and LC3 0 immunoreactivities were significantly higher than those in the other groups (p<0.05). The lowest p62 immunoreactivity was observed in the 25 mg/kg ATX + I/R group. Conclusions: ATX had a protective effect on kidney function and against oxidative damage. Furthermore, high-dose ATX administration protected kidney tissue via autophagy induction in this study.Öğe Investigation of the Effect of Astaxanthin on Oxidative Stress in Renal Ischemia-Reperfusion Modeled Rats(Wiley, 2022) Kisaoglu, Aysegul; Kose, Evren; Yilmaz, Nesibe; Tanbek, Kevser; Yilmaz, Umit; Ozbag, Davut[No abstract available]Öğe Neuroprotection by melatonin against acrylamide-induced brain damage in pinealectomized rats(Elsevier, 2022) Bicer, Yasemin; Elbe, Hulya; Karayakali, Melike; Yigitturk, Gurkan; Yilmaz, Umit; Cengil, Osman; Al Gburi, Mohammed Raed AbdullahThe current study aimed to evaluate the neuroprotective effect of exogenous melatonin against acrylamide (ACR)-induced oxidative stress and inflammatory and apoptotic responses in the brain tissues in pinealectomized rats (PINX). ACR is a toxic chemical carcinogen that occurs owing to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. The rats who underwent pinealectomy and sham pinealectomy were exposed to ACR (25 mg/kg b.w., orally) alone or with exogenous melatonin (10 mg/kg b.w., i.p.) for 21 consecutive days. Alterations of brain oxidant/antioxidant status, dopamine (DA), Brain-Derived Neurotropic Factor (BDNF) inflammatory mediator and apoptosis during exposure to ACR in pinealectomized rats were more than without pinealectomized rats. Histopathological changes were more in brain tissue of pinealectomized rats after ACR administration. Exogenous melatonin treatment in ACR-exposed rats following pinealectomy increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS) compared to PINX+ACR. Moreover, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in ACR-intoxicated brain tissues. In addition, after exposure to ACR on pinealectomized rats, melatonin treatment ameliorated BDNF and DA levels in brain tissues. Furthermore, exogenous melatonin intervention in ACR-intoxicated rats significantly rescued the architecture of neuronal tissues. In summary, the present study, for the first time, suggested that exogenous melatonin treatment could reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological alterations in the brain tissue of pinealectomized rats after ACR administration.Öğe Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by ?-naphthylthiourea(Taylor & Francis Ltd, 2023) Al Gburi, Mohammed Raed Abdullah; Altinoz, Eyup; Elbe, Hulya; Onal, Melike Ozgul; Yilmaz, Umit; Yilmaz, Nesibe; Karayakali, MelikeWe aimed to observe the possible effects of melatonin (MLT) deprivation (pinealectomy) and exogenous MLT administration on pulmonary edema induced by alpha-naphthylthiourea (ANTU), a toxic chemical agent, in rats. Seventy animals were assigned to seven groups: control, sham pinealectomy (PINX), PINX, ANTU (10 mg/kg intraperitoneal on day 30), ANTU + MLT (10 mg/kg/day i.p. for 30 days), ANTU + PINX, and ANTU + PINX + MLT. In this study, pleural effusion (PE) formation, lung weight/body weight (LW/BW) and PE/BW ratios (fluid accumulation and weight values in the lungs) increase detected. Pre-ANTU MLT administration led to significant decreases in PE, LW/BW, and PE/BW levels. The inhibited glutathione (GSH) and superoxide dismutase (SOD) levels and high malondialdehyde (MDA) levels that ANTU increase lipid peroxidation in the study. MLT administration eliminated oxidative stress by reducing MDA and ameliorating GSH and SOD levels. Pre-ANTU MLT administration led to a significant decrease in interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) levels in the lung when compared to the ANTU group without MLT administration. Post-pinealectomy ANTU administration significantly increased IL-1 beta and TNF-alpha levels when compared to ANTU and MLT administration without pinealectomy. Diffused inflammatory cell infiltration, interstitial pulmonary edema, and histopathological congestion were observed after the administration of ANTU. Severity of the damage was elevated in the ANTU + PINX group. MLT treatment regressed pulmonary effusion and edema and improves lung structure. In brief, the findings suggested that MLT inhibited proinflammatory mediators and could serve as a therapeutic agent to prevent inflammatory disorders.Öğe Protective effect of astaxanthin on testis torsion/detorsion injury through modulation of autophagy(Mre Press, 2024) Yilmaz, Nesibe; Yildiz, Azibe; Tanbek, Kevser; Kisaoglu, Aysegul; Yilmaz, Umit; Kose, EvrenA significant clinical condition known as testicular torsion leads to permanent ischemic damage to the testicular tissue and consequent loss of function in the testicles. In this study, it was aimed to evaluate the protective effects of Astaxanthin (ASTX) on testicular damage in rats with testicular torsion/detorsion in the light of biochemical and histopathological data. Spraque Dawley rats of 21 were randomly divided into three groups; sham, testicular torsion/detorsion (TTD) and astaxanthin + testicular torsion/detorsion (ASTX + TTD). TTD and ASTX + TTD groups underwent testicular torsion for 2 hours and then detorsion for 4 hours. Rats in the ASTX + TTD group were given 1 mg/kg/day astaxanthin by oral gavage for 7 days before torsion. Following the detorsion process, oxidative stress parameters and histopathological changes in testicular tissue were evaluated. Malondialdehyde (MDA) and total oxidant status (TOS) levels were significantly decreased in the ASTX group compared to the TTD group, while superoxide dismutase (SOD), glutathione (GSH) and total antioxidant status (TAS) levels were increased ( p < 0.05). Moreover, histopathological changes were significantly reduced in the group given ASTX ( p < 0.0001). It was determined that ASTX administration increased Beclin-1 immunoreactivity in ischemic testicular tissue, while decreasing caspase-3 immunoreactivity ( p < 0.0001). Our study is the first to investigate the antiautophagic and antiapoptotic properties of astaxanthin after testicular torsion/detorsion based on the close relationship of Beclin-1 and caspase-3 in ischemic tissues. Our results clearly demonstrate the protective effects of ASTX against ischemic damage in testicular tissue. In ischemic testicular tissue, ASTX contributes to the survival of cells by inducing autophagy and inhibiting the apoptosis.Öğe Spexin may induce mitochondrial biogenesis in white and brown adipocytes via the hypothalamus-pituitary-thyroid (HPT) axis(Pergamon-Elsevier Science Ltd, 2024) Yilmaz, Umit; Tanbek, KevserAim: The present study aimed to investigate the effect of the intracerebroventricular (icv) administration of spexin on the hypothalamus-pituitary-thyroid (HPT) axis (TRH, TSH, T4 and T3 hormones) and energy expenditure (PGC-1 alpha and UCP1 genes) in white adipose (WAT) and brown adipose tissues (BAT) in rats. Furthermore, the study aimed to determine the effects of spexin on food-water consumption and body weight of rats.Material and method: The study was conducted with 40 male rats that were divided into 4 groups: Control, Sham, Spexin 30 and Spexin 100 (n = 10). Spexin (1 mu l/hour) was administered to rats other than those in the control group for 7 days with osmotic minipumps intracerebroventricularly, artificial cerebrospinal fluid (vehicle) was administered to the Sham group, and 30 nMol and 100 nMol spexin was infused to the Spexin 30 and Spexin 100 groups, respectively. Food-water consumption and body weight of the rats were monitored during the experiments. After the seven-day infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined with ELISA on rat blood samples. Also, TRH gene expression levels from the hypothalamus tissues and PGC-1 alpha and UCP1 expression levels from WAT and BAT were determined by real-time PCR.Findings: It was determined that icv spexin infusion reduced daily food consumption and body weight without leading to a significant change in water consumption (p < 0.05). Icv spexin infusion significantly decreased serum TSH, and increased fT4 and fT3 levels when compared to control and sham groups (p < 0.05). Moreover, icv spexin infusion increased the TRH expressions in the hypothalamus tissues and PGC-1 alpha UCP1 in the WAT and BAT (p < 0.05).Conclusion: Icv Spexin infusion may have effects on food consumption and body weight as well as, thyroid hormones and energy metabolism.
