Person: YEGEN, BERRAK
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YEGEN
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BERRAK
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Publication Open Access Ghrelin Treatment Improves Lipid Metabolism and Hepatic Degeneration in Ovariectomized Rats(GAZI UNIV, FAC MED, 2020-01-01) YEGEN, BERRAK; Gurler, Esra Bihter; Ozbeyli, Dilek; Kaya, Ozlem Tugce Cilingir; Ercan, Feriha; Yegen, Berrak C.Objective: Metabolic disorders occurring in post-menopausal period increase the risk for development of fatty liver disease in women. Aim of the study was to evaluate possible effects of ghrelin on metabolic biomarkers and hepatic morphology in ovariectomized (OVT) rats. Methods:Under ketamine-chlorpromazine anesthesia (100 mg/kg, 0.75 mg/kg), Sprague-Dawley rats (n=12) underwent bilateral OVT, while control group had sham-surgery (n=6). Four weeks after surgery, half of OVT rats were treated intraperitonally with ghrelin (1 mg/kg/hafta) for 4 weeks, while others were not treated. Rats were euthanized by cardiac puncture at the end of 8th weeks, and serum levels of glucose, insulin, aspartate aminotransferase (AST), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, estradiol and progesterone were measured by an automated analyzer. Results: Increased body weights in OVT rats (p<0.001) recorded at the end of 2 months was not changed with ghrelin. Serum estradiol and progesterone levels were reduced (p<0.05) verifying altered gonadal hormone status, but insulin and glucose levels were not changed. Reduced HDL and increased LDL levels (p<0.0.5) were evident in non-treated OVX rats, while ghrelin treatment depressed LDL levels (p<0.0.5), but did not change HDL levels. However, ghrelin in OVT rats depressed triglycerides, VLDL and AST levels significantly (p<0.05). Moderate sinusoidal congestion, activated Kupffer cells and hepatocytes with ballooning degeneration was observed in non-treated OVT rats, while significant improvements were present in livers of ghrelin-treated rats. Conclusion: In conclusion, mild dyslipidemia and hepatic degeneration in early post-menopausal period appear to be attenuated by ghrelin treatment, and require further investigation.Publication Open Access High-fat Diet Enhances Gastric Contractility, but Abolishes Nesfatin-1-induced Inhibition of Gastric Emptying(KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY, 2021-04-30) YEGEN, BERRAK; Ozdemir-Kumral, Zarife N.; Koyuncuoglu, Turkan; Arabaci-Tamer, Sevil; Cilingir-Kaya, Ozlem T.; Koroglu, Ayca K.; Yuksel, Meral; Yegen, Berrak C.Neither HFD nor NES-1 changed methylcellulose emptying, but NES-1 delayed saline emptying in cannulated ND-rats. Inhibitory effect of NES-1 on gastric emptying in ND-rats was reversed by all antagonists, and abolished in HFD-rats. In HFD-rats, carbachol-induced contractility was enhanced in gastric, but inhibited in ileal strips. HFD increased body weight, while serum triglycerides, alanine transaminase, aspartate aminotransferase, glucose, and levels of malondialdehyde, glutathione, myeloperoxidase activity, and luminolchemiluminescence in hepatic, ileal, and adipose tissues were similar in ND- and HFD-rats, but only lucigenin-chemiluminescence was Background/Aims Gastrointestinal motility changes contribute to development and maintenance of obesity. Nesfatin-1 (NES-1) is involved in central appetite control. The aim is to elucidate effects of NES-1 and high-fat diet (HFD) on gastrointestinal motility and to explore myenteric neuron expressions of tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), and neuronal nitric oxide synthase (nNOS) in HFDinduced oxidative injury. Methods Sprague-Dawley rats were fed with normal diet (ND) or HFD. Gastric emptying rate was measured following NES-1 (5 pmol/rat, intracerebroventricular) preceded by subcutaneous injections of glucagon-like peptide 1 (GLP-1), cholecystokinin 1 (CCK-1), and gastrin/CCK-2 receptor antagonists. In carbachol-contracted gastric and ileal strips, contractile changes were recorded by adding NES1 (0.3 nmol/L), GLP-1, CCK-1, and gastrin/CCK-2 antagonists. Results Neither HFD nor NES-1 changed methylcellulose emptying, but NES-1 delayed saline emptying in cannulated ND-rats. Inhibitory effect of NES-1 on gastric emptying in ND-rats was reversed by all antagonists, and abolished in HFD-rats. In HFD-rats, carbachol-induced contractility was enhanced in gastric, but inhibited in ileal strips. HFD increased body weight, while serum triglycerides, alanine transaminase, aspartate aminotransferase, glucose, and levels of malondialdehyde, glutathione, myeloperoxidase activity, and luminolchemiluminescence in hepatic, ileal, and adipose tissues were similar in ND-and HFD-rats, but only lucigenin-chemiluminescence was increased in HFD-rats. Vasoactive intestinal peptide (VIP) and TH immunoreactivities were depressed and nNOS immunoreactivity was increased in gastric tissues of HFD-rats, while VIP and TH were enhanced, but nNOS was reduced in their intestines. Conclusions HFD caused mild systemic inflammation, disrupted enteric innervation, enhanced gastric contractility, inhibited ileal contractility, and eliminated inhibitory effect of NES-1 on gastric motility. (J Neurogastroenterol Motil 2021;27:265-278)Publication Open Access The gastroprotective effect of obestatin on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism(AKADEMIAI KIADO ZRT, 2020-06) YEGEN, BERRAK; Sen, Leyla Semiha; Kumral, Zarife Nigar Ozdemir; Memi, Gulsun; Ercan, Feriha; Yegen, Berrak C.; Yegen, CumhurIn order to investigate the role of the vagus nerve in the possible gastroprotective effect of obestatin on the indomethacin-induced acute oxidative gastric injury, Sprague-Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg, 5% NaHCO3) followed by obestatin (10, 30 or 100 mu g/kg). In other sets of rats, surgical vagotomy (Vx) or selective degeneration of vagal afferent fibers by perivagal capsaicin was performed before the injections of indomethacin or indomethacin + obestatin (30 mu g/kg). Gastric serosal blood flow was measured, and 4 h after ulcer induction gastric tissue samples were taken for histological and biochemical assays. Obestatin reduced the severity of indomethacin-induced acute ulcer via the reversal of reactive hyperemia, by inhibiting ulcer-induced neutrophil infiltration and lipid peroxidation along with the replenishment of glutathione (GSH) stores, whereas Vx abolished the inhibitory effect of obestatin on blood flow and lipid peroxidation, and worsened the severity of ulcer. On the other hand, serosal blood flow was even amplified by the selective denervation of the capsaicin-sensitive vagal afferent fibers, but obestatin-induced reduction in ulcer severity was not altered. In conclusion, the gastroprotective effect of obestatin on indomethacin-induced ulcer appears to involve the activation of the vagovagal pathway.Publication Open Access A 10-day mild treadmill exercise performed before an epileptic seizure alleviates oxidative injury in the skeletal muscle and brain tissues of the rats(2022-01-01) KAYA, ÖZLEM TUĞÇE; YEGEN, BERRAK; YÜKSEL, MERAL; YILDIRIM, ALPER; Arabaci -Tamer S., KAYA Ö. T., YÜKSEL M., YILDIRIM A., YEGEN B.© 2022 Marmara University Press, All Rights Reserved.Objective: Epileptic seizures may cause skeletal muscle injury and memory dysfunctions. The present study was aimed to investigate the possible protective effects of exercising prior to seizure on seizure-induced oxidative injury in the skeletal muscle and brain. Materials and Methods: Sprague-Dawley male rats were assigned as non-exercise (n=16) and exercise groups (n=16). Following a 3-day exercise training, exercise protocol (30 min) was performed on a treadmill for 10 days, while control rats had no exercise. On the 11th day, the epileptic seizure was induced by a single intraperitoneal injection of pentylenetetrazol (PTZ) (45 mg/kg), while the control groups were injected with saline. Passive-avoidance test was initially performed before PTZ/saline injection and repeated 72 h later for the assessment of memory function. Brain and gastrocnemius muscles were taken for histological assessments and to determine the levels of malondialdehyde (MDA) and glutathione (GSH), myeloperoxidase (MPO) activity and luminal – and lucigenin – enhanced chemiluminescence levels. Results: Exercise training alone increased the formation of reactive oxygen species and elevated the antioxidant GSH capacity of the muscle tissue in the control rats, but these effects were not observed in the muscles of the exercised rats induced with a PTZ-seizure. On the other hand, short-term exercise alone had no effect on the basal oxidative parameters of the brain tissues. Prior exercise did not alter the average seizure scores or memory performances when compared to non-exercised groups, but suppressed the PTZ-induced elevations in MDA and chemiluminescence levels as well as MPO activity in the brain. Conclusion: A 10-day mild treadmill exercise reduced the oxidative brain damage due to a single seizure-induced excitotoxicity and exerted a preconditioning effect on the skeletal muscles exposed to tonic-clonic contractions.Publication Open Access Punica Granatum Peel Extract Protects Against Ionizing Radiation-Induced Enteritis And Leukocyte Apoptosis In Rats(OXFORD UNIV PRESS, 2009) YEGEN, BERRAK; Toklu, Hale Z.; Sehirli, Oezer; Ozyurt, Hazan; Mayadagli, A. Alpaslan; Eksioglu-Demiralp, Emel; Cetinel, Sule; Sahin, Huelya; Yegen, Berrak C.; Dumlu, Melek Ulusoylu; Gokmen, Vural; Sener, GoekselApoptosis/Cytokine/Enteritis/Ileum/Irradiation/Punica granatum/Pomegranate/Radioprotective. Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a potential to support a Successful radiotherapy by protecting against radiation-induced enteritis.Publication Open Access Nicorandil preserves blood-brain barrier and improves memory impairment in hypertensive rats(MARMARA UNIV, 2019-11-15) YEGEN, BERRAK; Cevikelli Yakut, Zatiye Ayca; Ertas, Busra; Koyuncuoglu, Turkan; Yegen, Berrak C.; Sener, GokselIn renovascular hypertension (RVH), oxidative stress and inflammation due to high blood pressure and elevated levels of angiotensin 2 are mainly responsible of cerebrovascular complications and impaired cognitive functions. Since the nicorandil has been shown to exert neuroprotective, anti-inflammatory and antioxidant effects, we investigated the effect of nicorandil against vascular dementia and blood brain barrier damage in a rat model of angiotensin-dependent hypertension. Wistar albino rats, were divided as sham-operated control, renovascular hypertension (RVH) and Nicorandil-treated RVH groups. Silver clip was implanted onto the left renal artery. Using the tail-cuff method, blood pressure of rats was measured before the surgery and at the end of the post-surgical 3rd and 12th weeks. Nicorandil (4mg/kg, orally) or vehicle was administered for 9 weeks. Twelve weeks after RVH surgery, a new object recognition test was performed. Following the determination of blood brain barrier integrity, serum samples were taken for the evaluation of proinflammatory cytokines tumor necrosis alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Levels of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), as a marker of endothelial damage, were evaluated in the hippocampal tissues. RVH resulted in significant increases in TNF-alpha and IL-1 beta levels and decreases in Na+/K+-ATPase levels, along with impairment in blood brain barrier integrity and memory performance. In the nicorandil treatment group, these indices were reversed back to control levels. The present data demonstrated that nicorandil attenuates RVH-induced memory impairment and blood brain barrier damage in rats with RVH.