Browsing by Author "Bağdaş, Deniz"
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Item Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain(Blackwell Publishing, 2018-01) Ergün, D.; Jackson, A.; Toma, W.; Schulte, M. K.; Damaj, M. I.; Bağdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; 15062425700BackgroundNeuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. The 42 subtype of nAChRs plays an important role in the mediation of pain and several nicotine-evoked responses. Agonists and partial agonists of 42 nAChRs show efficacy in animal pain models. In addition, the antinociceptive properties of nicotine, a non-selective nAChR agonist with a high affinity for 42 nAChRs, is well-known. There is a growing body of evidence pointing to allosteric modulation of nAChRs as an alternative treatment strategy in experimental pain. Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) at 42 nAChRs that enhances agonist responses without activating receptors. We hypothesized that dFBr may enhance nicotine-induced antinociception. MethodsThe present study investigated whether dFBr could attenuate mouse chronic constriction injury (CCI)-induced neuropathic pain by increasing endogenous cholinergic tone or potentiating the nicotine-evoked antiallodynic response. ResultsWe found that subcutaneous administration of dFBr failed to reduce pain behaviour on its own. However, the combination of dFBr with nicotine significantly reversed neuropathic pain behaviour dose- and time-dependently without motor impairment. Our data revealed that this effect was mediated by the 42 nAChRs by using competitive 42 antagonist dihydro--erythroidine. In addition, dFBr failed to potentiate the antiallodynic effect of morphine, which shows the effect of dFBr is unique to 42 nAChRs. ConclusionsThe present results suggest that allosteric modulation of 42 nAChR may provide new strategies in chronic neuropathic pain. Significance42 nAChRs are involved in pain modulation. dFBr, a PAM at 42 nAChRs, potentiates the nicotine response dose-dependently in neuropathic pain. Thus, the present results suggest that allosteric modulation of 42* nAChR may provide new strategies in chronic neuropathic pain.Item The antihyperalgesic effect of cytidine-5 '-diphosphate-choline in neuropathic and inflammatory pain models(Lippincott Williams & Wilkins, 2011-09) Bağdaş, Deniz; Sonat, Füsun Ak; Hamurtekin, Emre; Sonal, Songül; Gürün, Mine Sibel; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Veterinerlik Fakültesi/Farmakoloji ve Toksikoloji Anabilim Dalı; Uludağ Üniversitesi/Veterinerlik Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0001-9018-1842; K-3299-2019; ABI-4237-2020; AAG-8716-2019; 15062425700; 26428428000; 8717648500; 7801642676; 55664349700This study was designed to test the effects of intracerebroventricularly (i.c.v.) administered CDP-choline (cytidine-5'-diphosphate-choline; citicoline) and its metabolites in rat models of inflammatory and neuropathic pain. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 mu mol) produced a dose and time-dependent reversal of mechanical hyperalgesia in both carrageenan-induced inflammatory and chronic constriction injury-induced neuropathic pain models in rats. The antihyperalgesic effect of CDP-choline was similar to that observed with an equimolar dose of choline (1 mu mol). The CDP-choline-induced antihyperalgesic effect was prevented by central administration of the neuronal high-affinity choline uptake inhibitor hemicholinium-3 (1 mu g), the nonselective nicotinic receptor antagonist mecamylamine (50 mu g), the alpha 7-selective nicotinic ACh receptor antagonist, alpha-bungarotoxin (2 mu g) and the gamma-aminobutyric acid B receptor antagonist CGP-35348 (20 mu g). In contrast, i.c.v. pretreatment with the nonselective opioid receptor antagonist naloxone (10 mu g) only prevented the CDP-choline-induced antihyperalgesic effect in the neuropathic pain model while the nonselective muscarinic receptor antagonist atropine (10 mu g) did not alter the antihyperalgesic effect in the two models. These results indicate that CDP-choline-elicited antihyperalgesic effect in different models of pain occurs through mechanisms that seem to involve an interaction with supraspinal alpha 7-selective nicotinic ACh receptors, and gamma-aminobutyric acid B receptors, whereas central opioid receptors have a role only in the neuropathic pain model. Behavioural Pharmacology 22:589-598 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.Item The antinociceptive and antiinflammatory properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of α7 nicotinic acetylcholine receptors in mice(Lippincott Williams & Wilkins, 2015-11) Targowska-Duda, Katarzyna M.; Lopez, Jhon J.; Perez, Edwin G.; Arias, Hugo R.; Damaj, M. Imad; Bağdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme Uygulama Merkezi.; 0000-0002-7353-0155; 15062425700BACKGROUND: Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective 7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative 7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS: We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant-induced inflammatory pain, and the chronic constriction injury-induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective 7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid-induced aversion by using the conditioned place aversion test. RESULTS: We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by 7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective 7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid-induced aversion in the conditioned place aversion assay. CONCLUSIONS: These findings suggest that the administration of PAM-2, a new 7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain.Item Antinociceptive effect of chlorogenic acid in rats with painful diabetic neuropathy(Mary Ann Liebert, 2014-06) Bağdaş, Deniz; Özbölük, Hasret Yücel; Çinkılıç, Nilüfer; Gürün, Mine Sibel; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Birimi.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-3595-6286; AAG-8716-2019; AAH-5296-2021; 15062425700; 55890590200; 26533892300; 55664349700The present study aimed to evaluate possible antinociceptive effects of chlorogenic acid in streptozotocin-induced diabetic neuropathic pain in rats. Chlorogenic acid (100 mg/kg) was administered daily for 14 days. Our study showed for the first time that both single and chronic chlorogenic acid treatments produced significant antinociceptive effects in diabetic rats. In contrast, single dose of chlorogenic acid showed no signs of an antinociceptive effect, but chronic treatment exerted antinociceptive potential in nondiabetic rats. Additionally, chronic treatment effectively reduced hyperglycemia that induced by diabetes. In conclusion, chlorogenic acid has beneficial effects for the management of diabetic neuropathic pain.Item Chlorogenic acid enhances abdominal skin flap survival based on epigastric artery in nondiabetic and diabetic rats(Lippincott Williams & Wilkins, 2014-06-06) Bağdaş, Deniz; Etöz, Betül Çam; Gül, Zülfiye; Özyiğit, Musa Özgür; Çinkılıç, Nilüfer; İnan, Sevda; Büyükcoşkun, Naciye İsbil; Özlük, Kasım; Gürün, Mine Sibel; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Eczacılık Anabilim Dalı.; Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-3595-6286; 0000-0001-8138-5851; 0000-0002-8872-0074; AAF-9939-2020; AAH-5296-2021; E-3364-2018; AAR-6478-2021; AAH-1692-2021; AAG-8716-2019; AAH-2873-2021; 15062425700; 56427863700; 56086542900; 6507338060; 26533892300; 56320836200; 6603128152; 6602676331; 55664349700Previous studies showed that chlorogenic acid (CGA) accelerates wound healing via its antioxidant activity. We aimed to investigate the effect of CGA in an experimental epigastric abdominal skin flap model in nondiabetic and diabetic rats. Rats were firstly divided into 2 groups: nondiabetic and diabetic. Diabetes was induced by streptozotocin. Then, 4 subgroups were created for each group: vehicle as well as 0.2 mg/0.5 mL, 1 mg/0.5 mL, and 5 mg/0.5 mL CGA treatments. Right epigastric artery-based abdominal skin flaps were elevated and sutured back into their original position. Chlorogenic acid or vehicle was injected once into the femoral arteries by leaving the epigastric artery as the single artery feeding the flaps during the injection. On postoperative day 7, flap survivals were evaluated, and the rats were killed. Distal flap tissues were collected for histopathological and biochemical assays. Chlorogenic acid showed greater flap survival in both nondiabetic and diabetic rats. Capillary density was increased, and necrosis was reduced in the CGA-treated rats. Chlorogenic acid decreased malondialdehyde levels as well as increased reduced glutathione and superoxide dismutase levels in the flap tissues. This study showed that CGA significantly improved flap survival by its antioxidant activities with intra-arterial local injections.Item Cyanide poisoning deaths in dogs(Wiley-Blackwell Publishing, 2006) Oruç, Hasan Hüseyin; Yılmaz, Rasime; Bağdaş, Deniz; Özyiğit, Musa Özgür; Uludağ Üniversitesi/Veteriner Fakültesi/Farmakoloji ve Toksikoloji Anabilim Dalı.; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü.; Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; 0000-0002-5399-2395; AAR-6478-2021; AAI-2212-2021; 55944769400; 15057258600; 15062425700; 6507338060In 2005, the deaths of three dogs were reported in Erdek, Turkey. Examining appropriate historical and clinical signs, postmortem findings and the discovery of cyanide in their stomachs and intestinal contents and livers supported a diagnosis of cyanide poisoning.Item Deneysel inflamatuvar ağrı modelinde CDP-kolinin analjezik etkisi ve etki mekanizması(Uludağ Üniversitesi, 2008) Bağdaş, Deniz; Sonal, Songül; Gürün, M. Sibel; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Farmakoloji ve Toksikoloji Anabilim Dalı.CDP-kolin, vücutta endojen üretilen nükleotid yapısında bir bileşik olup, sıçanlarda akut ağrı modellerinde analjezik etkisi gösterilmiştir. Çalışmada; deneysel inflamatuvar ağrı modelinde CDP-kolin’in, carrageenan uygulamasına bağlı gelişen hiperaljezi ve pençe ödemi üzerine etkisi araştırıldı; analjezik etkileri değerlendirildi. Deneylerde Sprague-Dawley erkek sıçanlar kullanıldı. İlaçlar, tuzlu su içinde hazırlanarak intraserebroventriküler yolla 10 µl hacimde uygulandı. İnflamasyon, sıçanların sağ arka pençelerine intraplantar % 2’lik λ-carrageenan enjeksiyonu (100 µl) yapılarak oluşturuldu. İnflamatuvar ağrı duyarlılığı termal ve mekanik pençe çekme testleriyle, carrageenana bağlı gelişen pençe ödeminde pençe genişliği dijital mikrometreyle ölçülerek değerlendirildi. CDP-kolin (0.5, 1 ve 2 µmol) her iki testte doza ve zamana bağlı olacak şekilde antihiperaljezik etki oluşturdu. Antihiperaljezik etki eşmolar dozlardaki (1 µmol) kolin ve CDP-kolin uygulamasında benzer şekilde ortaya çıkarken; sitidin için aynı etki termal pençe çekme testinde görülmeyip, mekanik pençe çekme testinde 5. dakikada saptandı. CDP-kolin’in antihiperaljezik etkisi her iki testte de, uygulanan hemikolinium-3 (yüksek afiniteli kolin geri alım blokörü,1 µg), mekamilamin (seçici olmayan nikotinik reseptör antagonisti,50 µg), alfa-bungarotoksin (α7 nöronal nikotinik reseptör antagonisti, 2 µg) ve CGP-35348 (GABAB reseptör antagonisti, 20 µg) ön tedavileri ile baskılandı. Atropin (seçici olmayan muskarinik reseptör antagonisti, 10 µg) ve nalokson (seçici olmayan opioid reseptör antagonisti,10 µg) ön tedavileri ise CDP-kolin’in antihiperaljezik etkisini değiştirmedi. CDP-kolin’in (2µmol, intraserebroventriküler) carrageenana bağlı gelişen pençe ödemini azaltmadığı gözlemlendi. Elde edilen bulgular, sıçanlarda inflamatuvar ağrı modelinde CDP-kolin’in antihiperaljezik etki yaptığını ortaya koymuştur. Presinaptik kolinerjik mekanizmaların aktivasyonu aracılığıyla santral α7 nikotinik kolinerjik reseptörlerin uyarılması CDPkolin’in antihiperaljezik etkisindeki muhtemel mekanizma olarak görünmektedir. Santral GABAB reseptörler, CDP-kolin’in antihiperaljezik etkisinde rol oynarken; opioid reseptörlerin rolü görülmemiştir.Item (E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation(Taylor and Francis, 2021-07-27) Rabha, Younis; Han-Shen, Tae; Ortells, Marcelo O.; Arias, Hugo R.; Bağdaş, Deniz; Gül, Zülfiye; Sevdar, Gülce; Cavun, Sinan; Gürün, Mine Sibel; Uludağ Üniversitesi/Tıp Fakültesi/Sinir Bilimleri ve Nöroloji; 0000-0003-0307-3486; 0000-0001-5050-095X; JCN-7924-2023; AAC-9702-2019; DVX-8040-2022; 57226240379; 6507468595; 55664349700Clinical intervention of pain is often accompanied by changes in affective behaviors, so both assays of affective and sensorial aspects of nociception play an important role in the development of novel analgesics. Although positive allosteric modulation (PAM) of alpha 7 nicotinic acetylcholine receptors (nAChRs) has been recognized as a novel approach for the relief of sensorial aspects of pain, their effects on affective components of pain remain unclear. Therefore, we investigated whether PAM-4, a highly selective alpha 7-nAChR PAM, attenuates inflammatory and neuropathic pain, as well as the concomitant depressive/anxiety comorbidities. The anti-nociceptive activity of PAM-4 was assessed in mice using the formalin test and chronic constriction injury (CCI)-induced neuropathic pain model. The anxiolytic- and antidepressant-like activity of PAM-4 was evaluated using the marble burying test and forced swimming test. Acute systemic administration of PAM-4 dose-dependently reversed formalin-induced paw licking behavior and CCI-induced mechanical allodynia without development of any motor impairment. PAM-4 reversed the decreased swimming time and number of buried marbles in CCI-treated mice, suggesting that this ligand attenuates chronic pain-induced depression-like behavior and anxiogenic-like effects. The effects of PAM-4 were inhibited by the alpha 7-selective antagonist methyllycaconitine, indicating molecular mechanism mediated by alpha 7-nAChRs. Indeed, electrophysiological recordings showed the PAM-4 enhances human alpha 7 nAChRs with higher potency and efficacy compared to rat alpha 7 nAChRs. These findings suggest that PAM-4 reduces both sensorial and affective behaviors induced by chronic pain in mice by alpha 7-nAChR potentiation. PAM-4 deserves further investigations for the management of chronic painful conditions with comorbidities.Item Effect of high fructose corn sirup on pancreatic ductal adenocarcinoma induced by dimethyl benzantracene (DMBA) in rats(Routledge Journals, 2020-05-12) İnan, Sevda; Akgül, Mustafa Barış; Bağdaş, Deniz; Sinir-Özcan, Gülşah; Suna, Senem; Tamer, Canan Ece; Sönmez, Gürsel; Evrensel, Türkkan; Kaya, Ekrem; Sarandöl, Emre; Dündar, Halit Ziya; Tarım, Ömer Faruk; Ercan, İlker; Sığırlı, Deniz; İncedayı, Bige; Çopur, Ömer Utku; Bursa Uludağ Üniversitesi/Ziraat Fakültesi/Gıda Mühendisliği Bölümü.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Endokrinolojisi Anabilim Dalı.; 0000-0003-3954-0058; 0000-0002-6947-2167; 0000-0003-0441-1707; 0000-0003-1840-1825; 0000-0002-9732-5340; 0000-0002-9562-4195; 0000-0002-2593-7196; 0000-0002-7346-7440; 0000-0002-5322-5508; 0000-0002-2382-290X; 0000-0001-5871-8769; 0000-0001-6128-7453; 0000-0002-1951-7937; AAG-8277-2021; ABE-1716-2020; AAQ-8178-2020; AAJ-1027-2021; AAG-7319-2021; AAG-8503-2021; AAG-8336-2021; AAA-7472-2021; ABF-2367-2020; 57194441710; 55512747500; 8228159500; 55167435000; 6603942124; 7004568109; 55943324800; 55453773300; 6701427186Increased risk of pancreatic cancer may be associated with consumption of sugar containing foods. The aim of this study was to evaluate the effect of peach nectar containing high fructose corn sirup (HFCS) consumption in a pancreatic carcinogenesis rat model induced by 7,12-Dimethyl benzanthracene (DMBA). Fifty-day-old male Sprague Dawley rats were fed with peach nectar containing HFCS + chow, peach nectar containing sucrose + chow and only chow. After 8 mo, feeding period, each group was divided into two subgroups, in which the rats were implanted with DMBA and no DMBA (sham). Histologic specimens were evaluated according to the routine tissue processing protocol. The animals withad libitumaccess to pn-HFCS, pn-sucrose and chow (only) showed significant differences in chow consumption and glucose level. Necropsy and histopathologic findings showed tumor formation in the entire group treated with DMBA. Excluding one rat in chow group, which was classified as poorly differentiated type, the others were classified as moderately differentiated pancreatic ductal adenocarcinoma (PDAC). This study demonstrated that daily intake of HFCS did not increase body weight and there was no effect of peach nectar consumption on the development of PDAC induced by DMBA in rats.Item Effects of adrenomedullin and glucagon-like peptide on distal flap necrosis and vascularity: The role of receptor systems and nitric oxide(H. M. P. Commjnications, 2017-06) Cam, Betül; Bağdaş, Deniz; Özyiğit, Musa Özgür; Sağdilek, Engin; Büyükcoşkun, Naciye İsbil; Özlük, Kasım; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyofizik Anabilim Dalı.; AAH-1692-2021; AAH-2873-2021; AAR-6478-2021; AAH-4397-2021; 56427863700; 15062425700; 6507338060; 16835756600; 6603128152; 6602676331Objective. Flap necrosis in the distal area due to the deficiency of blood circulation is a major complication in flap treatment. In many previous studies, some natural substances such as chlorogenic acid, adrenomedullin (ADM), and glucagon-like peptide-1 (GLP-1) have been used to improve flap viability via their vasodilator, angiogenic, and antioxidant effects. The aim of this study is to clarify the mechanism through the use of selective antagonists for calcitonin gene-related peptide (CGRP) receptors and GLP-1,receptors such as CGRP-(8-37), exendin-(9-39), respectively, in the flap healing effects of ADM and GLP-1. The role of nitric oxide (NO) was investigated in the mechanism as well. Materials and Methods. Seventy adult female Wistar rats (200 g-250 g) were used in the study. The cutaneous skin flap (8 cm x 3 cm) on the abdominal wall was raised based on the superficial inferior epigastric artery (SIEA). Single-dose substance injections were administered into the SIEA. Necrosis in the flap area was evaluated on postoperative day 7. The proportion of the necrosis area (necrosis area % = [necrosis area/ flap area] x 100) and vascularity (vascular number/cm(2)) in the distal area were calculated. Results. The administrations of ADM or GLP-1 increased the vascularity and decreased the necrosis area in the distal flap region. The ADM receptor antagonist, CGRP-(8-37), did not prevent the positive effects of ADM on flap healing and vascularity. A GLP-1 receptor antagonist, exendin-(9-39), prevented the effect of GLP-1 on flap healing and vascularity. Nitric oxide mediated the beneficial effects of both peptides on flap healing. Conclusion. The CGRP receptors have no direct role, but NO acts as a mediator in the beneficial effect of ADM on flap healing. The GLP-1 specific receptors and NO act as important interagents for the effects of GLP-1 on flap healing.Item Effects of long-term consumption of high fructose corn syrup containing peach nectar on body weight gain in sprague dawley rats(Soc Brasileira Ciencia Tecnologia Alimentos, 2016-10-23) Sinir, Gülşah Özcan; Suna, Senem; İnan, Sevda; Bağdaş, Deniz; Tamer, Canan Ece; Çopur, Ömer Utku; Sığırlı, Deniz; Sarandöl, Emre; Sönmez, Gürsel; Ercan, İlker; Evrensel, Türkkan; Tarım, Ömer Faruk; Eren, Erdal; Uylaser, Vildan; İncedayı, Bige; Uludağ Üniversitesi/Ziraat Fakültesi/Gıda Mühendisliği Bölümü.; Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Endokrinolojisi Anabilim Dalı.; 0000-0003-3954-0058; 0000-0002-1684-1053; 0000-0001-8138-5851; 0000-0002-9732-5340; 0000-0002-2593-7196; 0000-0002-6947-2167; AAF-3324-2020; AAH-1155-2021; AAG-8336-2021; AAM-1734-2020; E-3364-2018; AAG-8503-2021; AAG-8277-2021; AAG-8241-2021; AAJ-1027-2021; ABE-1716-2020; AAG-8410-2021; AAQ-8178-2020; AAP-7233-2020; ABF-2367-2020; AAA-7472-2021; 57194441710; 55512747500; 56320836200; 15062425700; 8228159500; 8228159600; 24482063400; 55943324800; 55167435000; 6603789069; 6603942124; 6701427186High fructose corn syrup (HFCS) is one of the most used sweeteners in the food industry. Health concerns regarding the consumption of HFCS-containing foods have developed in parallel with the increasing amount of people who become overweight. This study was conducted to investigate whether HFCS-containing peach nectar (pn-HFCS) consumption has more detrimental effects on anthropometrical and biochemical parameters compared with sucrose-containing peach nectar (pn-sucrose). Fifty-day-old Sprague Dawley rats were divided into three groups and were fed (A) pn-HFCS + ad libitum chow, (B) pn-sucrose + ad libitum chow and (C) only ad libitum chow for 7 months. The percentage change in body weight (PCBW), body mass index (BMI), and Lee index were calculated, and serum triglyceride, glucose, insulin and leptin concentrations were measured. The PCBW, BMI, Lee index, serum triglyceride, glucose, insulin and leptin concentrations were insignificant among the three groups. We can suggest that peach nectar consumption resulted in more energy intake than the control and since pn-HFCS group consumed more chow than the pn-sucrose group. The results show that long term daily HFCS or sucrose consumption in peach nectar is not associated with weight gain and does not stimulate metabolic changes in Sprague Dawley rats.Item The effects of menthol-nicotine usage on gastric mucosal damage and the investigation of possible mechanisms(Wiley, 2016-09) Şahintürk, Serdar; Gül, Zülfiye; Çam, Betül; Bağdaş, Deniz; Büyükcoşkun, Naciye İsbil; Özlük, Kasım; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Birimi.; AAH-1692-2021; AAF-9939-2020; CGO-3719-2022; DQA-8365-2022; EOB-5882-2022Item Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice(Pergamon-Elsevier, 2014-10) Zhu, Andy Z.X; Muldoon, Pretal P.; Tyndale, Rachel F.; Damaj, Mohamad Imad; Bağdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Birimi.; 15062425700Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the principal pathway by which active nicotine is removed from circulation. We therefore hypothesized that inhibition of mouse CYP2A5, the ortolog of human CYP2A6, by methoxsalen (8-methoxypsoralen) alter dependence-related behaviors of nicotine in the mouse. Conditioned place preference (CPP) test was used to assess the appetitive reward-like properties and precipitated nicotine withdrawal to assess physical (somatic and hyperalgesia) and affective (anxiety-related behaviors) measures. The nicotine plasma levels were also measured with or without methoxsalen pretreatment. Methoxsalen (15 and 30 mg/kg, intraperitoneally) pretreatment enhanced nicotine-induced preference in mice (p < 0.05). However, there was a lack of enhancement of nicotine in the CPP test after the highest dose of the CYP-2A5 inhibitor. Similarly to the CPP results, repeated administration of methoxsalen increased the intensity of mecamylamine-precipitated withdrawal signs. The potentiation of nicotine preference and withdrawal intensity by methoxsalen was accompanied by significant increase in nicotine plasma levels in mice (p < 0.05). Finally, methoxsalen enhanced the ability of a very low dose of nicotine (0.05 mg/kg) to reverse withdrawal signs in mice undergoing spontaneous withdrawal after chronic nicotine infusion (p < 0.05). In conclusion, inhibition of nicotine metabolism by methoxsalen alters the behavioral effects of nicotine in the mouse. Combining CYP2A6 inhibitors with low dose nicotine replacement therapies may have a beneficial role in smoking cessation because it will decrease the drug elimination rate and maintain plasma and brain nicotine levels.Item Effects of nicotine metabolites on nicotine withdrawal behaviors in mice(Oxford University, 2017-06) Elhassan, Sagi; Damaj, M.Imad; Bağdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; 15062425700Introduction: Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Methods: Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Results: Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. Implications: The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence.Item Effects of systemic chlorogenic acid on random-pattern dorsal skin flap survival in diabetic rats(Pharmaceutical Soc Japan, 2014-03) Bağdaş, Deniz; Çam, Betül Etöz; İnan, Sevda; Çinkılıç, Nilüfer; Özyiğit, Musa Özgür; Gül, Zülfiye; Büyükcoşkun, Naciye; Özlük, Kasım; Gürün, Mine Sibel; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Birimi.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Veterinerlik Fakültesi/Klinik Öncesi Bilimler Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı.; 0000-0002-3595-6286; 0000-0001-8138-5851; 0000-0002-8872-0074; AAF-9939-2020; AAH-5296-2021; AAH-2873-2021; AAH-1692-2021; E-3364-2018; AAG-8716-2019; 15062425700; 24179406800; 56320836200; 26533892300; 6507338060; 56086542900; 55665951400; 6602676331; 55664349700There has been considerable interest in understanding the effects of antioxidants in flap survival during diabetes. Previous studies showed that chlorogenic acid (CGA) exhibits potent antioxidant effects. We aimed to determine the effects of systemic CGA treatment on skin flap survival in an experimental random-pattern dorsal skin flap model in diabetic rats. Twenty-eight male Wistar rats were divided into four groups: phosphate buffered saline (PBS)-treated or CGA-treated nondiabetic rats, PBS-treated or CGA-treated diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg). Caudally based bipedicled dorsal skin flaps were elevated. CGA (100 mg/kg) or PBS (mL/kg; as vehicle) was administered intraperitoneally once daily. On postoperative day 7, flap survival, regional blood perfusion and microangiography were evaluated. The malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated from the flap tissue. Capillary density and vascular endothelial growth factor (VEGF) expression were assessed. Harmful effects of diabetes on flap survival were observed. CGA attenuated these effects and allowed greater survival and blood perfusion. CGA decreased MDA and NO levels and increased GSH and SOD levels. CGA elevated capillary density and VEGF expression. This study showed that peripherally administered CGA significantly improved flap survival in diabetic and nondiabetic rats.Item Expression and pharmacological modulation of visceral pain-induced conditioned place aversion in mice(Elsevier, 2016-03) Muldoon, Pretal P.; AiSharari, Shakir; Carroll, F. Ivy; Negus, S. Stevens; Damaj, M. Imad; Bağdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; 15062425700Pain encompasses both a sensory as well as an affective dimension and these are differentially processed in the brain and periphery. It is therefore important to develop animal models to reflect the non-reflexive assays in pain. In this study, we compared effects of the mu opioid receptor agonist morphine, the nonsteroidal anti-inflammatory drug ketoprofen and the kappa receptor opioid agonist U50,488H and antagonist JDTic on acetic acid-induced stretching and acetic acid-induced aversion in the condition place aversion (CPA) test in male ICR mice. Intraperitoneal administration of acetic acid (0.32-1%) was equipotent in stimulating stretching and CPA. Ketoprofen, morphine and U50,488H all inhibited the acid induced stretching. Ketoprofen and morphine also blocked the acid-induced CPA but U50,488H failed to do so. The reversal ability of ketoprofen and morphine on acid-induced CPA is unique to pain-stimulated place aversion since these drugs failed to reduce non-noxious LiCl-induced CPA. Overall, this study characterized and validated a preclinical mouse model of pain-related aversive behavior that can be used to assess genetic and biological mechanisms of pain as well as improving the predictive validity of preclinical studies on candidate analgesics.Item Expression and pharmacological modulation of visceral pain-induced conditioned place aversion in mice(Wiley, 2016-04) AlSharari, Shakir; Muldoon, Pretal; Carroll, Ivy; Negus, Stevens; Damaj, Imad; Bağdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Toksikoloji Anabilim Dalı.; EOB-5882-2022Item Genotoxic and anti-genotoxic effects of vanillic acid against mitomycin c-induced genomic damage in human lymphocytes In vitro(Asian Pacific Journal of Cancer Prevention, 2012) Erdem, Merve Güler; Cinkılıç, Nilüfer; Vatan, Özgür; Yılmaz, Dilek; Bağdaş, Deniz; Bilaloğlu, Rahmi; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; 0000-0002-7687-3284; 0000-0002-3595-6286; O-7508-2015; AAH-5296-2021; 57084393100; 26533892300; 16235098100; 6701369462; 15062425700; 6505804122Vanillic acid, a vegetable phenolic compound, is a strong antioxidant. The aim of the present study was to determine its effects on mitomycin C-induced DNA damage in human blood lymphocyte cultures in vitro, both alone and in combination with mitomycin C (MMC). The cytokinesis block micronucleus test and alkaline comet assay were used to determine genotoxic damage and anti-genotoxic effects of vanillic acid at the DNA and chromosome levels. MMC induced genotoxicity at a dose of 0.25 mu g/ml. Vanillic acid (1 mu g/ml) significantly reduced both the rates of DNA damaged cells and the frequency of micronucleated cells. A high dose of vanillic acid (2 mu g/ml) itself had genotoxic effects on DNA. In addition, both test systems showed similar results when tested with the negative control, consisting of dimethyl sulfoxide (DMSO) in combination with vanillic acid (1 mu g/ml)+MMC. In conclusion, vanillic acid could prevent oxidative damage to DNA and chromosomes when used at an appropriately low dose.Publication Genotoxic and cytotoxic effects of the aglepristone, a progesteron antagonist, in mid-gestation pregnancy termination in rabbits(Kafkas Univ, Veteriner Fakultesi Dergisi, 2015-03-01) Vatan, Özgür; Bağdaş, Deniz; Çinkılıç, Nilüfer; Wehrend, Axel; Özalp, Gözde Rabia; VATAN, ÖZGÜR; Bagdas, Deniz; ÇİNKILIÇ, NİLÜFER; ÖZALP, RABİA GÖZDE; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; Uludağ Üniversitesi/Veteriner Fakültesi/Jinekoloji Anabilim Dalı.; 0000-0002-7687-3284; 0000-0002-3595-6286; 0000-0003-4694-6937; ISV-0209-2023; O-7508-2015; AAH-5296-2021; AAE-3607-2019; EOB-5882-2022Aglepristone is an antiprogestin using for pregnancy termination in veterinary medicine. The information about side effects of aglepristone is limited. The aim of the study was to investigate cytotoxicity and genotoxicity of aglepristone in mid-gestation pregnancy termination in rabbits. Fifteen New Zealand White rabbits were used and pregnant does were randomly divided into three groups. Group I (n=5) was treated with saline as the control. The does in group II (n=5) and group III (n=5) were treated with aglepristone (10 mg/kg) on 15th day and 15th-16th days of pregnancy, respectively. The rabbits were sacrificed by guillotine 24 h after last treatment. Bone marrow and blood samples were immediately collected. Cytotoxic and genotoxic potential were tested by micronucleus and Comet assays. No genotoxicity and cytotoxicity were found in micronucleus test with single aglepristone administration. In contrast, two consecutive treatments of aglepristone showed high genotoxic and cytotoxic effects on bone marrow in animals. While comet assay of blood samples did not show any significant difference between groups; the results from comet assay of bone marrow cells showed the single injection of aglepristone did not induce any DNA damage but two injections group increased the DNA damage.Item Impact of menthol on oral nicotine consumption in female and male sprague dawley rats(Oxford University Press, 2019-02-05) Bağdaş, Deniz; Gül, Zülfiye; Scott, Michael M.; Tyndale, Rachel F.; Damaj, M. Imad; Cam, Betül; Büyükuysal, Levent; Gürün, Mine Sibel; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; AAH-1657-2021; CGO-3719-2022; DVX-8040-2022; 56427863700; 6602686612; 55664349700Introduction: One of the preferable flavors in oral nicotine delivery systems is menthol which masks the harshness of tobacco. However, possible interactions between oral menthol and nicotine on intake and preference remain unclear. Therefore, we aimed to determine the impact of menthol on oral nicotine consumption. Methods: Adult Sprague Dawley female and male rats (n = 8 per group) were given a choice of water or drug solution by using two-bottle free choice paradigm for 2 weeks: vehicle (5% ethanol), nicotine (20 mg/L), menthol (1 g/L) and mentholated nicotine groups. At the end of the study, plasma nicotine levels were determined. Results: When rats were given a choice of nicotine or water, nicotine intake was similar between female and male rats. Menthol addition to nicotine solution significantly increased nicotine intake and preference in male but not female rats without a considerable effect on total fluid intake and body weight change in either sex. The average nicotine intake in male rats was 0.5 +/- 0.05 and 1.4 +/- 0.12 mg/kg/day for nicotine and menthol-nicotine combination (p <.05), respectively. The average nicotine intake in female rats was 0.6 +/- 0.05 and 0.6 +/- 0.03 mg/kg/day for nicotine and mentholnicotine combination (p >.05), respectively. Plasma nicotine levels were not significantly different between the groups in either male (nicotine group: 20.8 +/- 4.9, mentholated nicotine group: 31.9 +/- 3.2 ng/mL) or female (nicotine group: 24.0 +/- 3.3, mentholated nicotine group: 17.8 +/- 2.9 ng/mL) rats (p >.05). Conclusions: Menthol increases oral nicotine consumption in male, but not female, rats.