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Aim: Menopause is defined as the depletion of the ovarian follicular reserve followed by the cessation of menstrual cycles. It has been reported that gonadal steroid hormones play an important role in bladder function in women. Changes in urine pattern including overactive bladder, stress incontinence and recurrent urinary tract infections occur as a result of menopause. 1,1-dimethylbiguanide hydrochloride, metformin, (MET) is an oral anti-diabetic drug used to reduce hepatic glucose production and peripheral insulin resistance. Recent studies have revealed that MET has a protective effects in diabetes induced bladder dysfunction. The aim of this study was to test the therapeutic potential of MET in detrusor contractile function of ovariectomized (OVX) female rats. Material and Methods: Bilateral ovariectomy was performed to eliminate endogenous gonadal steroids secretion. Four groups are designed with 8 animals in each group: Control, MET-administered control, OVX, and MET-administered OVX groups. MET (25 mg/ kg) was administered daily by oral gavage for 14 days. Contractile activity of isolated bladder muscle strips were evaluated in vitro organ bath. The contractile responses of detrusor strips were determined using different doses of carbachol (10-8-10-2M) and purinergic agonist ATP. The relaxation response of strips were determined by isoproterenol Results: The contractile responses of detrusor muscle strips to carbachol at doses 10-5-10-2 M were decreased in the OVX group compared to control and MET treated control groups. MET treatment partially reversed the reduction in OVX-induced contractile responses at 10-2 and 10 -3 M carbachol doses. There were no statistically significant difference in relaxation response between the experimental groups. Conclusion: Our findings suggest that treatment with MET could be the new potential therapeutic agent against bladder dyfunction in postmenopausal women. Further studies are needed for the therapeutic potential of MET in detrusor dysfunction induced by menopause.

Amaç: Glukagon benzeri peptit-1 (GLP-1), enteroendokrin L hücrelerinden salgılanan önemli bir inkretin hormondur. GLP-1 analogları,diyabet ve obezite tedavisi için kullanılmaktadır. Ovaryan hormonların kardiyovasküler fonksiyonların düzenlenmesinde etkili roloynadığı iyi bilinmektedir. Postmenopozal kadınlarda kardiyovasküler hastalık insidansı artar. Bu çalışmanın amacı, yumurtalıklarıalınmış sıçanlarda GLP- 1 analoğu olan liraglutid uygulanmasının kardiyak fonksiyonlar ve kalp dokusu oksidatif stres üzerindekietkisini araştırmaktır.Gereç ve Yöntemler: Çalışmada otuz iki genç dişi Wistar albino sıçan kullanıldı. Denekler rastgele kontrol, liraglutid ile tedavi edilenkontrol, yumurtalıkları alınan (OVX) ve liraglutid ile tedavi edilen OVX gruplarına ayrıldı. İki aylık dişi sıçanlarda ovariektomi ve sahtecerrahi işlemler uygulandı. Ovariektomi operasyonundan beş hafta sonra liraglutid tedavisi (150μg/kg, deri altı, 14 gün) başlandı. 14günlük süre sonunda kalp atım hızı ve kan basıncı ölçümleri yapıldıktan sonra hayvanlar sakrifiye edildi, kahverengi ve beyaz yağ dokusuağırlıkları ile kalp dokusu malondialdehit (MDA), indirgenmiş glutatyon (GSH), nitrat, glikojen ve askorbik asit seviyeleri ölçüldü.Bulgular: Kalp hızı açısından tüm gruplar arasında fark bulunmazken, liraglutid uygulanan gruplarda kan basıncı istatistiksel olarakanlamlı derecede azaldı. MDA ve askorbik asit seviyeleri tüm gruplar arasında önemli bir değişim gözlenmedi. GSH seviyeleri liraglutidile tedavi edilen OVX grubunda arttı. Ovariektomi ile kalp dokusunda nitrat düzeylerinin azaldığı saptandı. Kardiyak glikojen düzeyiOVX ve liraglutid uygulanan OVX grubunda kontrol grubuna göre artmış olarak bulunmuştur. Liraglutid tedavisi kalpteki nitratmiktarını kontrol seviyelerinde korudu. Ek olarak, liraglutid uygulaması OVX sıçanlarında retroperitoneal yağ birikimini azalttı.Sonuç: Sonuçlarımız GLP-1 uygulamasının ovariektominin neden olduğu kan basıncı artışı ve kalp dokusunda azalan GSH seviyelerinikorumada etkili olduğu bulunmuştur. Bu nedenle, GLP-1 analogları, postmenopozal dönemde kan basıncının düzenlenmesindepotansiyel terapötik ajan olarak kabul edilebilir., Aim: Glucagon-like peptide 1 (GLP-1) is an important incretin hormone secreted from enteroendocrine L cells. GLP-1 analogs areused for the treatment of diabetes and obesity. Ovarian hormones are well known in playing critical roles in regulating cardiovascularfunctions. Cardiovascular disease incidence increases in postmenopausal women. The aim of this study was to investigate the effect ofadministration of liraglutide, a GLP 1 analogue, on cardiac function and cardiac tissue oxidative stress in ovariectomized rats.Material and Methods: Thirty two young female Wistar albino rats were used in the study. Subjects were randomly divided into control,liraglutide-treated control, ovariectomized (OVX), and liraglutide-treated OVX groups. Ovariectomy and sham surgical procedures wereperformed in 2-month-old female rats. Liraglutide treatment (150μg/kg, subcutaneous, 14 days) was started five weeks after the ovariectomyoperation. After measuring the heart rate and blood pressure at the end of the 14-day period, the animals were sacrificed, brown and whiteadipose tissue weights, and heart tissue malondialdehyde (MDA), reduced glutathione (GSH), nitrate, glycogen and ascorbic acid levelswere measured.Results: While there was no difference between all groups in terms of heart rate, blood pressure was statistically significantly decreasedin the liraglutide-administered groups. MDA and ascorbic acid levels did not change significantly between all groups. GSH levelswere increased in the liraglutide-treated OVX group. It was found that the cardiac glycogen level was increased in the OVX grouptreated with OVX and liraglutide compared to the control group. Nitral levels in the heart tissue were found to be decreased withovarectomy. Liraglutide treatment maintained nitrate levels in the heart at control levels. In addition, liraglutide administration reducedretroperitoneal fat deposition in OVX rats.Conclusion: Our results showed that GLP-1 administration was effective in reducing the increased blood pressure due to ovariectomyand maintaining the decreased GSH level in the heart tissue.. Therefore, GLP-1 analogs can be considered as potential therapeutic agentsin the regulation of blood pressure in the postmenopausal period.

Amaç: Diabetes mellitus (DM) kronik hiperglisemi ile karakterize metabolik bir hastalıktır. Bu çalışmanın amacı, melatoninin DM’lisıçanlarda iskelet kası ve kalp kası üzerindeki etkilerini değerlendirmektir.Gereç ve Yöntemler: 36 erkek Wistar albino rat kontrol grubu, kontrol + melatonin grubu, Diyabet grubu, Diyabet + melatonin grubuolarak 4 gruba ayrıldı. Melatonin (10 mg / kg, ip) tedavisi dört hafta süreyle uygulandı. Malondialdehit (MDA) seviyeleri ve indirgenmişglutatyon seviyeleri (GSH) ile Nrf2 ve tiyoredoksin (TRX) seviyeleri değerlendirildi.Bulgular: Diyabetik grubun iskelet ve kalp kası MDA düzeyleri kontrol gruplarına göre yüksek bulunurken, melatonin tedavisi ile budeğer anlamlı düzeyde azalmıştır (p, Aim: Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. The goal of this study was to assess the effects of melatonin on skeletal muscle and heart muscle in rats with DM.Material and Methods: 36 male Wistar albino rats were divided into 4 groups as control group, control+melatonin group, Diabetes group, Diabetes+melatonin group. Melatonin (10 mg/kg, ip) treatment was administered for four weeks. Malondialdehyde (MDA) level, reduced glutathione levels (GSH), Nrf2 and thioredoxin (TRX) levels were assessed.Results: Skeletal and heart muscle MDA levels of the diabetic group were increased than the control groups and melatonin treatment was remarkably decreased this value. (p

Aim: Chronic cerebral hypoperfusion (CCH) leads to vascular dementia with progressive hippocampal damage and cognitive impairments.CCH also causes a decrease in blood flow in the retina.The aim of this study was to investigate the effects of spironolactone on oxidativestress and glycogen levels in the eye and prefrontal cortex (PFC) tissues in ovariectomized rats with CCH.Material and Methods: 32 female Wistar Albino rats were randomly divided into 4 groups, 8 in each group: 1)Control, 2)KSH, 3)KSH+Spironolactone 25mg/kg 4)KSH+Spironolactone 50mg/kg. The rats underwent bilateral ovariectomy (OVX) at the start of theexperiment, a CCH model was created with permanent occlusion of the common carotid arteries (2VO) 5 weeks after OVX. Spironolactonewas administered by oral gavage three days before 2VO and once daily for 3 weeks after 2VO. At the end of the experiment, tissue glycogen,reduced glutathione (GSH), malondialdehyde (MDA) and ascorbic acid (AA) levels were measured. Statistical analysis was performed usingANOVA and Bonferroni tests.Results: CCH caused an increase in oxidative stress markers and a decrease in glycogen level in PFC. Similarly, CCH caused a decreasein both glycogen and AA levels in the eye tissue. In the group treated with 25mg/kg spironolactone, the AA and PFC glycogen levels of theeyes decreased, while the MDA levels in the PFC were increased compared to the CCH group(p, Amaç: Kronik serebral hipoperfüzyon (KSH), ilerleyici hipokampal hasar ve bilişsel bozukluklarlabirlikte vasküler demansa yol açar. KSH retinadaki kan akımında da azalmaya neden olmaktadır. Buçalışmanın amacı KSH oluşturulmuş overektomize sıçanlarda spironolaktonun göz ve prefrontal korteks(PFC) dokularındaki oksidatif stres ve glikojen seviyelerine etkilerini araştırmaktır.Gereç ve Yöntemler: Wistar Albino cinsi 32 adet dişi sıçan, her grupta 8 adet olacak şekilde rastgele4 gruba ayrıldı: 1)Kontrol, 2)KSH, 3)KSH+Spironolakton 25mg/kg 4)KSH+Spironolakton 50mg/kg.Sıçanlara deneyin başlangıcında bilateral ovariektomi (OVX) uygulandı, OVX’ten 5 hafta sonra ortakbilateral ortak karotid arter oklüzyonu (2VO) ile KSH modeli oluşturuldu. Spironolakton 2VO’dan üç günönce ve 2VO’dan sonra 3 hafta boyunca günde 1 kez oral gavaj yoluyla uygulandı. Deney sonundadoku glikojen, indirgenmiş glutatyon (GSH), malondialdehid (MDA) ve AA düzeyleri ölçüldü. İstatistikselanaliz ANOVA ve Bonferroni testleri kullanılarak yapıldı.Bulgular: KSH, PFC’de oksidatif stres belirteçlerinde artışa ve glikojen düzeyinde bir azalmaya nedenoldu. Benzer şekilde KSH göz dokusunda hem glikojen hem de AA düzeyinde azalmaya neden oldu.Spironolaktonun 25 mg/kg dozu ile tedavi edilen grupta KSH grubuna kıyasla göz AA ve PFC glikojendüzeyleri azalırken PFC’deki MDA düzeyi artmış olarak bulundu (p

Ovariectomized (OVX) rodents show behavioral despair and anxiety-like behaviors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) possess neuroprotective effects by reducing oxidative stress and neuroinflammation, thereby preventing synaptic loss. The objective of the present study is to evaluate the effect of GLP-1RA, namely liraglutide, on emotional behaviors, and to identify the level of oxidative stress, neuroinflammation, and BDNF signaling in the hippocampus of OVX rats. Forty female young Wistar rats were divided into 5 groups: Control, Control+liraglutide treated, OVX, OVX+fluoxetine, and OVX+liraglutide (150 µg/kg for 15 days, sc). Open field test and elevated plus-maze test were used to evaluate behaviors that are suggestive of anxiety. A forced swimming test was used to evaluate behavioral despair. At the end of the experiments, blood glucose level and body weight gain were measured. The levels of BDNF, CREB, Nrf2, and lipocalin 2 in the hippocampal tissue were measured by ELISA. Malondialdehyde (MDA) and glutathione levels were also evaluated. Statistical analysis was conducted through ANOVA and Bonferroni tests. Seven weeks post-OVX rats exhibited high anxiety related behavior and behavioral despair in comparison with the control groups. These behavioral changes were associated with increased lipocalin 2 and MDA levels in rats. Moreover, BDNF, CREB, and Nrf2 levels decreased significantly in the hippocampus of OVX rats. Liraglutide treatment limited the reduction of BDNF and Nrf2 levels in the hippocampus, maintaining them at the control levels. Liraglutide treatment also prevented the symptoms of behavioral despair and anxiety related behavior. As the main finding of the study GLP-1RA reduced behavioral despair and anxiety level and this may be related to the preservation of BDNF/Nrf2 levels and the decrease in oxidative stress and lipocalin 2 levels in the hippocampus.

Amaç: Çevresel zenginleştirmenin iskemiye veya travmaya bağlı gelişen patolojilerdehasarı azalttığı çeşitli çalışmalar tarafından gösterilmiştir. Bilateralkarotid arter oklüzyonu (2VO) kapiller damar hasarına, özellikle optik sinir veretinada dejenerasyona neden olmaktadır. Bu çalışmanın amacı çevreselzenginleştirmenin 2VO yapılan sıçanlarda retinal oksidatif stres ve C vitamini üzerineetkisini incelemektir.Gereç ve Yöntemler: Çalışmada 24 adet Wistar albino erkek sıçan(250-300 g) kullanıldı. Denekler rasgeleolmak üzere kontrol, 2VO+standart çevre (N), ve 2VO+zenginleştirilmiş çevre(EE) olarak 3 gruba ayrıldı. 2VO kalıcı bilateral karotid arter oklüzyonu ilegerçekleştirildi ve EE 4 hafta boyunca uygulandı. Deney sonunda göz dokularındamalondialdehid (MDA), indirgenmiş glutatyon (GSH) ve askorbik asit düzeyleriölçüldü. Bulgular: Çevresel zenginleştirme standart çevre grubu ilekarşılaştırıldığında retinal MDA seviyelerini azalttı. 2VO göz dokusunda,kontrol grubu ile karşılaştırıldığında GSH düzeylerini ve C vitamini miktarınıdüşürdü. (p0.05).Sonuç: Bu çalışmanın sonuçları çevresel zenginleştirmenin 2VO ile retinadaoluşan oksidatif stresi azaltmada etkili olabileceğini göstermektedir., Aim: Various studies have shown that environmental enrichment reduces the tissue damage in ischemia or trauma-related pathologies. Bilateral carotid artery occlusion (2VO) leads to capillary vessel damage, especially degeneration of the optic nerve and retina. The aim of this study was to investigate the effect of environmental enrichment on retinal oxidative stress and vitamin C in 2VO rats. Material and Methods: 24 Wistar Albino male rats (250-300 g) were used in the study. The rats were randomly separated into 3 groups as the control, 2VO+ standart environment (SE), 2VO+ environmental enrichment (EE). 2VO was induced by permanent bilateral carotid artery occlusion and EE was performed for 4 weeks. At the end of this period malondialdehyde (MDA), reduced glutathione (GSH) and ascorbic acid levels were measured in eye tissues. Results: Environmental enrichment reduced retinal MDA levels compared with the standard environmental group. 2VO decreased GSH levels and vitamin C compared with control group in eye tissues. EE ameliorated GSH levels compared to standard environmental group. However, EE did not affect retinal ascorbic acid levels. Conclusion: The results of this study show that environmental enrichment may be effective in reducing 2VO induced oxidative stress in the retina.

Aim: Diabets mellitus is associated with impaired learning and memory. Neuroinflammation is a pathophysiological hallmark of diabetes which include production of cytokines. It was suggested that nitrative injury has been implicated in the pathophysiologic mechanism of diabetes. Nod-like receptor family pyrin domain-containing (NLRP) inflammasomes are important in the development of inflammatory response through production of IL-1β and IL-18. In the present study was aimed to examine the relationship between NLRP3, IL-1 β, nitrotyrosine levels and cognitive functions in diabetic rats. Material and Methods: The rats were randomly divided into 2 groups: control and diabetic. Diabetes was induced by a single intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). Body weight and blood glucose level were measured until euthanasia. Morris water maze (MWM) was used to evaluate the cognitive function in rats. Hippocampal NLRP3, IL-1 β and nitrotyrosine levels were measured. Results: The results showed that the elevated blood glucose was obseved in diabetic group. NLRP3 and nitrotyrosine levels were found to be increased in hippocampus of diabetic rats. There was no statsitical significance in the hippocampal IL-1β level with diabetes. In the MWM, diabetic rats spent more time to find the submerged platform when compared with control rats, implying a significant impairment of learning and memory, and this impairment was found to be statistically signifcant at day 5. Conclusion: Our results indicate that STZ induced diabetes causes learning and memory impairment in rats probably by generating nitrosative stress and increasing NLRP3 level in the hippocampus.

Amac: Bu calisma cevresel zenginlestirmenin (EE) kronik serebral hipoperfuzyonla (KSH) olusturulan vaskuler demans modelinde depresyon benzeri davranis, serebral korteks ve hipokampusde beyin kaynakli norotrofik faktor (BDNF), kaspaz-1 ve IL-1β seviyeleri uzerine etkisini incelemek icin tasarlanmistir. Daha onceki calismalar EE’nin KSH modelinde oksidatif stres inhibisyonu ve endojen norokoruyucu faktorlerin artirilmasini iceren yararli etkilere sahip oldugunu gostermislerdir. Gerec ve Yontemler: KSH sicanlarda bilateral ortak karotid arterlerin okluzyonu ile olusturulmustur. Hayvanlar 3 gruba ayrilmistir: Sham, standart kafes kosullari ve 4 hafta boyunca zenginlestirilmis kosullara maruz birakilan grup. Sukroz tercih testi ve zorlu yuzme testi (FST) KSH sonrasi depresif davranisi degerlendirmek icin kullanilmistir. BDNF, IL-1β ve kaspaz-1 duzeylerindeki degisim incelenmistir. Bulgular: KSH, hipokampusde BDNF seviyesinde azalmaya, IL-1β ve kaspaz-1 duzeylerinde artis ile birlikte depresyon benzeri davranisa neden olmustur.. Sonuc: EE serebral hipoperfuzyon durumunda inflamatuar yaniti azaltarak ve BDNF seviyelerini koruyarak depresif davranisi iyilestirmede farmakolojik olmayan yeni bir strateji olabilir.

Several studies have shown that low estrogen levels can lead to an increase in the incidence of depression and anxiety during menopause. The hippocampus and prefrontal cortex are parts of the brain involved in depressive- and anxiety-like behaviors. Recent studies have revealed that metformin has neuroprotective effects mainly due to its antioxidant properties. The aim of the present study was to examine the therapeutic potential of metformin in depressive- and anxiety-like behavior as well as oxidative stress in the prefrontal cortex and hippocampus of ovariectomized rats. Young female Wistar Albino rats were distributed into four groups (n:8): control, metformin-administered control, ovariectomized and metformin administered ovariectomized groups. Metformin (25 mg/kg) was administered daily by oral gavage for 2 weeks. Forced swimming test and open field test were performed to evaluate depression- and anxiety-like behaviors, respectively. Following the treatment with metformin, the tissues of the hippocampus and prefrontal cortex were isolated for the measurement of malondialdehyde, reduced glutathione and ascorbic acid contents. Ovariectomy resulted in depressive- and anxiety-like behaviors, and besides, increased content of malondialdehyde in both prefrontal cortex and hippocampus. The levels of ascorbic acid and glutathione were found to be reduced in ovariectomized rats. Metformin treatment significantly decreased depressive behaviour and malondialdehyde content in the prefrontal cortex. Reducing oxidative stress of the prefrontal cortex was suggested as a possible mechanism implicated in the beneficial effects of metformin on ovariectomy-induced depressive-like behaviour. We believe that the therapeutic efficiency of metformin needs to be tested for potential clinical use in surgical menopause or gonadal hormone deficiency women with depression.

Cesitli deneysel calismalarda l-3,3′,5- triiodotronin (T3) veya ltiroksin (T4) onkosullanmasinin karaciger, beyin, kalp ve bobrek iskemi reperfuzyon (I/R) hasarina karsi koruyucu etkili oldugu gosterilmistir. Intestinal I/R hasari, genellikle sok, akut mezenterik iskemi, sepsis, mezenterik tromboz veya bagirsak nakli gibi bircok klinik durumun neden oldugu kritik bir tablodur. Bu calismanin amaci T3 ile olusturulan onkosullanmanin intestinal I/R ile olusan ince bagirsak ve akciger dokusundaki hasara karsi olasi koruyucu etkisini incelemektir. Erkek Wistar Albino cinsi sicanlara 30 dakika mezenterik iskemi ve sonrasinda 3 saat reperfuzyon uygulandi. Her grupta 8 hayvan olmak uzere 4 gruba ayrildilar: sham kontrol, I/R kontrol, I/R +50µg/kg T3 uygulanan ve I/R+100µg/kg T3 uygulanan grup. Intestinal ve akciger dokusundaki hasar histopatolojik olarak incelenmistir. Sonuclarimiz ince bagirsak ve akciger dokusunda 100 µg/kg dozunda T3 onkosullanmasinin I/R ile olusan patolojik degisikleri azalttigini gostermektedir. I/R grubunda hem akciger hem de intestinal dokuda histopatolojik hasar degerlendirmesinin yuksek seviyesinde oldugu bulunmustur. 100 µg I/R +T3 uygulanan grupta intestinal mukoza ve akciger hasarinin I/R ve I/R +50µg T3 uygulanan gruba gore dusuk oldugu saptanmistir. Sonuc olarak, intestinal I/R hasarindan once T3 ile olusturulan onkosullanmanin bagirsak iskemisinin neden oldugu ince bagirsak ve akciger dokusu uzerinde histopatolojik olarak koruyucu etkili oldugu gozlemlendi.

Diabetes is associated with depression and anxiety symptoms. The current investigation was designed to explore the effect of melatonin on depressive and anxiety like-behaviours, oxidative stress, levels of AGE, RAGE and S100B in streptozotocin-induced diabetic rats. The animals were divided into four groups: Normoglycemic; Normoglycemic + melatonin; diabetic; diabetic + melatonin (10 mg/kg, for 4 weeks). The malondialdehyde (MDA), reduced glutathione (GSH), AGE, RAGE and S100B were measured and the depressive and anxiety like-behaviours were assessed by forced swimming and elevated plus maze tests, respectively. Melatonin ameliorates depressive and anxiety like-behaviours. Concomitantly, melatonin reversed diabetes induced increase of MDA, AGE and decrease of GSH and S100B levels in the hippocampus and prefrontal cortex. In conclusion, our results showed that melatonin administration may exert antidepressant-like and anxiolytic effects in diabetic rats through normalising of AGE/RAGE, S100B and oxidative stress in the prefrontal cortex and hippocampus. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Intestinal iskemi/reperfuyon (I/R) akcigeri iceren coklu organ hasarina neden olmaktadir. Pulmoner doku hasari ve solunum yetmezligi intestinal iskemi sonrasi yaygin bir olaydir. Genel olarak serbest oksijen radikalleri (SOR) gibi oksidatif stres mediyatorlerinin I/R ile olusan pulmoner hasar gelisiminde rol oynadigina inanilmaktadir. Bu veriler isiginda, bu calismanin amaci, metformin tedavisinin sicanlarda intestinal I/ R ile induklenen akut akciger hasarini azaltip azaltmayacagini arastirmaktir. Intestinal I/R’nun sican modeli superior mezenterik arterin 45 dakika baglanmasi sonrasinda 3 saatlik reperfuzyonu ile olusturuldu. Metformin intestinal iskemiden 5 gun once oral olarak uygulandi (50,100 veya 200mg/kg dozunda). 40 adet Wistar Albino cinsi sican 5 gruba ayrildi: sham konrol, I/R kontrol ve metfornin uygulanan gruplar. Malondialdehid(MDA) ve indirgenmis glutatyon(GSH) seviyeleri oksidatif stresi degerlendirmek amaciyla olculdu. Hasari gozleyebilmek icin doku kesitleri hematoksilen eozin ile boyandi. Cesitli dozlarda metformin on tedavisi yapilan gruplarda tedavi edilmeyen I/R grubu ile karsilastirildiginda lipid peroksidasyon seviyesinin onemli olcude dustugu tespit edilmistir. 200mg/kg dozunda metformin on tedavisi yapilan grupta histopatolojik akciger hasar skorlari diger gruplarla karsilastirildiginda anlamli derecede azalmistir. Bunlara ek olarak metformin on tedavisi intestinal I/R sonrasinda akciger dokusunda GSH seviyelerini normalize etmistir. Bu calismanin sonuclari, metformin on tedavisinin intestinal I/R ile olusan akut akciger hasarini azaltmanin etkili bir yolu olabilecegini gostermektedir.

Intestinal iskemi reperfuzyon (I/R) hasari, cogu uzak organ sistemini etkileyen ve yuksek morbidite ve mortalite ile iliskili onemli klinik bir problemdir. Tirofiban; glikoprotein IIb/IIIa reseptor inhibitorudur ve deneysel I/R modellerinde koruyucu etkilerinin oldugu gosterilmistir. Bu calismada amacimiz tirofibanin intestinal I/R hasarindaki olasi etkilerini incelemektir. 24 adet Wistar Albino sican rasgele 3 gruba ayrildi. Kontrol grubundaki (n=8) sicanlara arter okluzyonu yapilmadan yalnizca laparotomi uygulandi. I/R grubundaki (n=8) sicanlarin superior mezenterik arterine 30 dk okluzyon ve ardindan 3 saat reperfuzyon uygulandi. I/R+Tirofiban grubundaki (n=8) sicanlara I/R uygulandi ve reperfuzyon oncesi intravenoz 200 μg/kg tirofiban verildi. Deney sonunda sicanlarin ileum dokulari alindi ve histopatolojik degisiklikler ile lipid peroksidasyon duzeyleri, indirgenmis glutatyon (GSH) duzeyleri ve miyeloperoksidaz (MPO) aktivitesi degerlendirildi. Intestinal dokunun histopatolojik hasar skoru, MPO aktivitesi, malondialdehid (MDA) duzeyleri I/R grubunda kontrol grubuna gore onemli bir artis gosterdi. GSH duzeyi I/R grubunda kontrol grubuna gore dusuk bulundu. Ancak, I/R+Tirofiban grubu ile I/R grubu karsilastirildiginda tum parametreler icin herhangi bir istatistiksel fark saptanmadi. Sonuc olarak, tirofiban tedavisi I/R nedenli intestinal hasari azaltamadi veya onleyemedi.

WOS: 000433886100005, PubMed: 29857826, Background: Intestinal ischemia and reperfusion (I/R) induces oxidative stress, inflammatory response, and acute lung injury. S-nitrosoglutathione (GSNO), a nitric oxide donor, has been documented to have protective effects on experimental ischemia models. Aim: The aim of this study was to examine the effect of GSNO on I/R-induced intestine and lung damage and detect the potential mechanisms emphasizing the protective role of GSNO. Methods: Intestinal I/R was induced by occluding the superior mesenteric artery for 30 min followed by reperfusion for 180 min. GSNO was administered intravenously before reperfusion period (0.25 mg/kg). The levels of lipid peroxidation, reduced glutathione, and myeloperoxidase (MPO), histopathological evaluation and immunohistochemical expressions of both nuclear factor KappaB (NF-kappa B) and inducible nitric oxide (iNOS) in intestine and lung tissues were assessed. Results: Histolopathologic evaluation demonstrated that intestinal I/R induced severe damages in the intestine and the lung tissues. Histopathological scores decreased with GSNO treatment. GSNO treatment reduced lipid peroxidation and MPO levels and inhibited expression of NF-kappa B and iNOS in the intestine. Conclusion: Our results suggest that GSNO treatment may ameliorate the intestinal and lung injury in rats, at least in part, by inhibiting inflammatory response and oxidative stress.

Amaç: Oksidatif stresin diyabetik komplikasyonların gelişiminde çok önemli rol oynadığı yaygın olarak kabul edilmektedir. Böylece koruyucu tedaviler hastalığın olası yan etkilerini hafifletebilir. Bu çalışmanın amacı melatonin tedavisinin diyabetik sıçanların karaciğer, böbrek, pankreas, mide ve retinal dokularındaki oksidan ve antioksidan durumuna etkisini incelemektir.Gereç ve Yöntemler: Erkek Wistar albino cinsi sıçanlar 4 gruba ayrıldılar: Kontrol, kontrol+melatonin, diyabetik ve diyabet+melatonin uygulanan grup. Sıçanlarda intraperitoneal (i.p) olarak tek doz streptozotosin (STZ) (60 mg/kg) uygulaması ile diyabet oluşturulmuştur. Melatonin 10 mg/kg dozunda günde tek doz i.p olarak 30 gün boyunca uygulanmıştır. 30 günlük tedavinin sonunda indirgenmiş glutatyon (GSH) ve malondialdehid (MDA) düzeyleri karaciğer, böbrek, pankreas, mide ve retinada ölçülmüştür.Bulgular: Sonuçlarımız diyabetik hayvanların dokularında MDA düzeylerinin arttığını ve GSH seviyelerinin azaldığını göstermiştir. Melatonin uygulaması karaciğer dışındaki dokularda MDA düzeylerini anlamlı olarak düşürmüştür. Melatonin tedavisi diyabet grubuna göre karşılaştırıldığında GSH düzeylerinde pankreas ve mide dışındaki dokularda artış bulunmuştur.Sonuç: Bu çalışmada sunulan sonuçlar, diyabete, diyabetik komplikasyonların başlıca nedeni olarak kabul edilen oksidatif stresin eşlik ettiği ortak görüşüyle uyumludur. Sonuçlarımız melatoninin diyabette artan oksidatif stres üzerinde iyileştirici etkisi ile kullanılabileceğini göstermektedir., Aim: It is commonly accepted that oxidative stress plays a crucial role in the development of diabetic complication. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of melatonin administration on the oxidant and antioxidant system in the liver, kidney, pancreas, stomach and retinal tissues of diabetic rats.Material and Methods: Male Wistar albino rats were randomly divided into 4 groups: control; control+Melatonin treatment; diabetic; diabetic+melatonin treatment. Rats were injected with a single intraperitoneal (i.p) injection of streptozotocin (STZ) (60 mg/kg) to induce diabetes mellitus. Melatonin (10 mg/kg) was given daily by i.p injection for 30 days. After 30 days of treatment, the contents of reduced glutathione (GSH) and malondialdehyde (MDA) in liver, kidney, pancreas, stomach and retina were assayed.Results: Our results showed that diabetic rats exhibited significant decreases in GSH level and exhibited a high level of MDA in tissues. Melatonin treatment significantly reduced the elevated MDA level all tissues except liver tissue. GSH levels were found to increase in all tissues except pancreas and stomach after melatonin treatment compared diabetes group.Conclusion: The results presented in this study are in agreement with the common view that diabetes is accompanied by oxidative stress, which is regarded as the main cause of diabetic complications. Our results suggests that melatonin could be used for its ameliorative effect against oxidative stress in diabetes

Aims Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Main methods Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10 mg/kg) was administered intraperitoneally before reperfusion period. After 180 min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. Key findings The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-?, and IL-1? were brought back to the sham control levels by the treatment as well. Significance Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. © 2017 Elsevier Inc., 2011-20-00-02, This work was supported by the research fund provided through Bulent Ecevit University [grant numbers 2011-20-00-02 ]. The authors express sincere gratitude to Eda Baki Zengin (Bulent Ecevit University, School of Foreign Languages) for providing language support.

Glucagon-like peptide-1(GLP-1) is a gut hormone secreted from L cells of the small intestine in response to food ingestion, and facilitates glucose-dependent insülin secretion. GLP-1 is also a neurotransmitter synthesized by a small population of neurons in the nucleus of the solitary tract in the caudal brainstem. Currently, the GLP-1 receptor agonists exendin-4, liraglutide and lixisenatide are approved for treatment of Type 2 diabetes mellitus (T2DM). The distribution of GLP-1 receptors in the brain suggests they play a central role in the regulation of neuronal activity and protect the brain tissue. Several studies have demonstrated the therapeutic effect of GLP-1 analog on animal models of Alzheimer disease, Parkinson disease and stroke. GLP-1 acts as a growth factor in the brain, and has been shown to induce neurite outgrowth and to protect against oxidative stress and reduces apoptosis. GLP-1 receptor agonists that cross the bloodbrain barrier can directly impact brain function independent of vagal afferent stimulation. It is clear that the central GLP-1 system plays a role in the regulation of food intake. Increasing evidence shows that central or peripheral GLP-1 administration reduces food intake in rodents and man. Furthermore, because of the suppression of appetite also induced by GLP‐1 and the subsequent bodyweight loss in response to the prolonged administration of the peptide, GLP‐1‐derivative drugs have also been approved for the treatment of obesity. In this review, the neuroprotective effects of GLP-1 in the nervous system and central effects on appetite were discussed, Glucagon-like peptid-1 (GLP-1) gıda alımına bağlı olarak ince bağırsaklarda bulunan L hücrelerinden salgılanır ve glukoz bağımlı insülin sekresyonuna neden olur. GLP-1 ayrıca beyin sapındaki nukleus traktus solitariusda (NTS) bulunan küçük bir nöron topluluğunda nörotransmitter olarak sentezlenmektedir. Şu anda exendin-4, liraglutide ve lixisenatide gibi GLP-1 reseptör agonitlerinin Tip 2 diabetes mellitus (T2DM) tedavisinde kullanılmaları onaylanmıştır. Beyinde dağılımı nedeniyle GLP-1 reseptörlerinin nöronal aktivitenin kontrolünde santral rol oynadığı ve beyin dokusunda koruyucu etkili olabileceğini öne sürülmüştür. Çeşitli çalışmalarda GLP-1 analoglarının deneysel Alzheimer hastalığı, Parkinson hastalığı ve inme modellerinde tedavi edici etkili olduğu bildirilmiştir. GLP-1 beyinde bir büyüme faktörü olarak etki eder ve nörit büyümesini sağlar, oksidatif stres ve apoptozisi azaltıcı etki göstermektedir. GLP-1 reseptör agonistleri kan beyin bariyerini geçebilir ve vagal affarent uyarımından bağımsız olarak beyin fonksiyonlarını etkiler. Santral GLP-1 sisteminin gıda alımının kontrolünde rol oynadığı açıktır. İnsan ve deney hayvanlarında periferal ve santral GLP-1 uygulamasının gıda alımını azalttığı artan kanıtlarla desteklenmektedir. Üstelik GLP-1 ile iştahın azaltılması ve uzun süreli bu peptid uygulamasının vücut ağırlığında azalmaya neden olması nedeniyle GLP-1 türevi ilaçların obezite tedavisinde kullanımları da onaylanmıştır. Bu derlemede GLP-1’in sinir sistemi üzerindeki koruyucu etkileri ve iştah üzerine olan santral etkileri tartışılmıştır.

WOS: 000341358100016, PubMed: 24862878, Background: Spironolactone (Sp), a mineralocorticoid receptor antagonist, protects against the ischemia reperfusion (IR) injury of retina, kidney, heart, and brain. We aimed to investigate the effects of Sp on intestinal IR injury. Methods: Male Wistar rats were randomly divided into: (1) a sham control group; (2) an IR control group, subjected to 30 min ischemia and 3 h reperfusion; (3) a group treated with Sp (20 mg/kg) for 3 d before the IR; and (4) a sham-operated control group treated with Sp (20 mg/kg). After the reperfusion, blood and intestinal tissue samples were collected to evaluate histopathologic state, neutrophil infiltration (by measuring myeloperoxidase activity), levels of the cytokines (tumor necrosis factor alpha, interleukin 1 alpha [IL-1 alpha], interferon gamma, monocyte chemotactic protein-1, granulocyte macrophage-colony stimulating factor, and IL-4), malondialdehyde (MDA) and reduced glutathione contents, and immunohistochemical expressions of nuclear factor kappa B, inducible nitric oxide synthase (iNOS), and caspase-3. Results: MDA content, myeloperoxidase activity, and plasma levels of tumor necrosis factor alpha, IL-1 alpha, and monocyte chemotactic protein-1 were all elevated in IR, indicating the oxidative stress and local and systemic inflammatory response. Sp administration markedly reduced the MDA content and the cytokine levels. The pretreatment alleviated intestinal injury, neutrophil infiltration, and the expressions of caspase-3, iNOS, and NF kappa B. Conclusions: The results implicate that Sp may have a strong protective effect against the intestinal IR injury. The effect can be mediated via suppression of both systemic inflammatory response and apoptosis through amelioration of oxidative stress and generation of proinflammatory cytokines, iNOS, caspase-3, and nuclear factor kappa B. Therefore, mineralocorticoid receptor antagonism might be of potential therapeutic benefit in cases of intestinal IR damage. (C) 2014 Elsevier Inc. All rights reserved.

Background: The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity. Materials and methods: Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation. Results: In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone. Conclusions: Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Purpose: Multiple organ failure, including acute lung injury, is a common complication of intestinal ischemia and reperfusion (I/R) injury and contributes to its high mortality rate. Activated polymorphonuclear neutrophils and reactive oxygen species contribute to the lung injury caused by intestinal I/R. Mineralokortikoid receptor antagonist spironolactone has a protective effect against I/R injury in animal models of retina, kidney, heart, and brain. The aim of the present study is to investigate the effect of aldosteron receptor blocker spironolactone on lung injury induced by intestinal I/R. Methods: Wistar albino rats were divided into four groups: (1) sham control; (2) intestinal I/R (30 min of ischemia by superior mesenteric artery occlusion followed by 3 h of reperfusion); (3) spironolactone pretreatment (20 mg/kg) + I/R; and, (4) spironolactone pretreatment without I/R. Spironolactone was given orally 3 days prior to intestinal I/R. A marker for lipid peroxidation (malondialdehyde; MDA), an indicator or oxidation state (reduced glutathione; GSH), an index of polymorphonuclear neutrophil sequestration (myeloperoxidase; MPO), inducible nitric oxide synthase (iNOS) immunoreactivity, and the histopathology of the lung tissue were analyzed. Results: Spironolactone pretreatment markedly reduced intestinal I/R-induced lung injury as indicated by histology and MDA and MPO levels. Moreover, the pretreatment decreased the iNOS immunoreactivity. Conclusion: The present study strongly suggests that spironolactone pretreatment decreased neutrophil infiltration, iNOS induction, oxidative stress, and histopathological injury in an experimental model of intestinal I/R induced-lung injury of rats.

Chronic cerebral hypoperfusion can cause learning and memory impairment and neuronal damage resembling the effects observed in vascular dementia. PPAR-γ agonists were shown to modulate inflammatory response and neuronal death following cerebral ischemia. The present study was designed to evaluate possible neuroprotective effects of rosiglitazone, a PPAR-γ agonist, in rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent bilateral occlusion of the common carotid arteries. Oral administration of rosiglitazone (1.5, 3, and 6 mg/kg/day) or vehicle was carried out for 5 weeks, starting one week before the surgery. Cognitive performance was assessed using the Morris water maze. The density of S100B protein-immunoreactive astrocytes and the OX-42-labeled microglial activation were estimated. Synaptogenesis was also evaluated by the measurement of synaptophysin, the pre-synaptic vesicular protein, level via western blotting technique. Cerebral hypoperfusion for 30 days induced a significant cognitive impairment along with hyperactivation of both microglial and astroglial cells, and reduction of synaptophysin level. Rosiglitazone treatment (3 and 6 mg/kg) not only suppressed the activation of astrocytes and microglia markedly but also alleviated the impairment of memory and increased the synaptophysin level. In conclusion, our results suggest that the chronic administration of rosiglitazone significantly prevents chronic cerebral hypoperfusion-induced brain damage, at least, partly through suppressing glial activation and preserving synaptic plasticity. Thus, it appears that rosiglitazone may be a promising pharmacological agent in the development of therapeutic approaches for the prevention or treatment of cerebrovascular diseases.

Oxidative stress is believed to contribute to functional and histopathologic disturbances associated with chronic cerebral hypoperfusion (CCH) in rats. Melatonin has protective effects against cerebral ischemia/reperfusion injury. This effect has mainly been attributed to its antioxidant properties. In the present study, we evaluate the effects of melatonin on chronic cerebral hypoperfused rats and examined its possible influence on oxidative stress, superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and heat shock protein (HSP) 70 induction. CCH was induced by permanent bilateral common carotid artery occlusion in ovariectomized female rats. Extensive neuronal loss in the hippocampus at day 14 following CCH was observed. The ischemic changes were preceded by increases in malondialdehyde (MDA) concentration and HSP70 induction as well as reductions in GSH and SOD. Melatonin treatment restored the levels of MDA, SOD, GSH, and HSP70 induction as compared to the ischemic group. Histopathologic analysis confirmed the protective effect of melatonin against CCH-induced morphologic alterations. Taken together, our results document that melatonin provides neuroprotective effects in CCH by attenuating oxidative stress and stress protein expression in neurons. This suggests melatonin may be helpful for the treatment of vascular dementia and cerebrovascular insufficiency. © 2009 John Wiley and Sons A/S.

One of common pathophysiological states associated with central nervous system is chronic cerebral hypoperfusion (CH) that frequently occurs in conditions such as vascular dementia and Alzheimer's disease. Long term blockage of angiotensin II type 1 (AT 1 ) receptor provides protection from ischemia induced injury of brain as well as reduction of cerebrovascular inflammation. Examining effect of the blockage on reduced glutathione (GSH), ascorbic acid (AA), and lipid peroxidation were of purpose in the present study. Modeling CH, rats were subjected to permanent occlusion of common carotid arteries bilaterally. AT 1 receptor antagonist, candesartan, was given daily for 14 days after surgery. CH caused a significant increase in lipid peroxidation and decrease in GSH content of cerebral hippocampal tissue with no change in AA level. Candesartan (0.5 mg/kg, oral) not only reduced lipid peroxidation but also restored GSH significantly besides elevating AA and improving histopathological alterations. In conclusion, long term AT 1 receptor blockage may be considered as novel therapeutic approach for protection from damage associated with CH. Underlying mechanism(s) may in part be related to suppressing oxidative stress and preserving brain antioxidant capacity. © 2007 Springer Science+Business Media, LLC.

Objectives: Resveratrol appears to have neuroprotective potential in various animal models of brain disorders including cerebral ischemia and neurodegenerative diseases. Chronic cerebral hypoperfusion is a well-known pathological condition contributing to the neurodegenerative diseases such as vascular dementia. Purpose of the present study is to evaluate the possible therapeutic potential of resveratrol in a model of vascular dementia of ovariectomized female rats. Assessment of the potential was based on the determination of brain oxidative status, caspase-3 level, glial fibrillary acidic protein (GFAP), and neuronal damage on hippocampus and cerebral cortex. Methods: For creating the model of chronic cerebral hypoperfusion, ovariectomized female Wistar rats were subjected to the modified two vessel occlusion method, with the right common carotid artery being occluded first and the left one a week later. Results: At the 15th day following the ligation, neuronal damage was accompanied by the increased immunoreactivities of both GFAP and caspase-3, and significant neurodegeneration was evident in the hippocampus and cortex, all of which were significantly alleviated with resveratrol treatment (10 mg/kg). Biochemical analysis revealed that the resveratrol treatment decreased lipid peroxidation and restored reduced glutathione level as well. Discussion: The collected data of the present study suggest that the administration of resveratrol may provide a remarkable therapeutic benefit for vascular dementia, which is most likely related to the prevention of both apoptotic cell death and oxidative stress. We believe that therapeutic efficacy of resveratrol deserves to be tested for potential clinical application in postmenopausal elderly women suffering from vascular dementia. © 2015 W. S. Maney & Son Ltd 2015.

Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and to damage of the nervous tissue. Melatonin, a main secretory product of the pineal gland, has free radical scavenging and antioxidant properties and has been shown to diminish I/R injury in many tissues. There are a limited number of studies related to the effects of melatonin on I/R injury in the peripheral nervous system. Therefore, in the present study, the protective effect of melatonin was investigated in rats subjected to 2 hr of sciatic nerve ischemia followed by 3 hr of reperfusion. Following reperfusion, nerve tissue samples were collected for quantitative assessment of malondialdehyde (MDA), an oxidative stress marker, and superoxide dismutase (SOD), a principal antioxidant enzyme. Samples were further evaluated at electron microscopic level to examine the neuropathological changes. I/R elevated the concentration of MDA significantly while there was a reduction at SOD levels. Melatonin treatment reversed the I/R-induced increase and decrease in MDA and SOD levels, respectively. Furthermore, melatonin salvaged the nerve fibers from ischemic degeneration. Histopathologic findings in the samples of melatonin-treated animals indicated less edema and less damage to the myelin sheaths and axons than those observed in the control samples. Our results suggest that administration of melatonin protects the sciatic nerve from I/R injury, which may be attributed to its antioxidant property.

The purpose of this study was to investigate the effects of staying at a moderate altitude (2,300 m, 7 d) on the levels of plasma nitrite, exhaled nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD). Measurements were obtained from 9 female (mean age 18.3 +/- 2) and 9 male (mean age 19.3 +/- 3.7) cross-country volunteer skiers: before, during (1st day, 7th day) and after staying at a moderate altitude. Exhaled nitric oxide levels were measured only before and after staying at the altitude. Nitrite levels increased throughout the stay at the altitude, while MDA levels decreased. In parallel with the nitrite levels, SOD activities were also found to have increased. Exhaled NO values were decreased after the stay at the moderate altitude. These results show that altitude hypoxia causes decreased in NO levels in the lung but increased systemic NO levels in the blood due to inhibition of erythrocyte lipid peroxidation.

WOS: 000231903200003, PubMed: 16176331, We investigated the combinative effects of l-arginine and melatonin on the contractile responses of terminal ileum after the intestinal ischemia-reperfusion (I/R), in vivo. Male rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (180 min). We have observed a dramatic decrease in spontaneous basal activity and Ach-induced contractile response. Our data clearly showed that the contractility decrease was ameliorated by l-arginine but not by l-NAME. Melatonin has reversed the inhibition of contractility caused by I/R injury in part. We did not observe an augmentation in the contractility of ileum when we use melatonin and l-arginine in combination, in fact, melatonin decreased the protective effect of l-arginine in intestinal I/R injury.

JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi o de investigar os efeitos da solução salina, da bupivacaína, lidocaína e da infiltração de tramadol na cicatrização de feridas em ratos. MÉTODOS: Trinta e dois ratos Wistar machos albinos foram alocados aleatoriamente em quatro grupos, que receberam 3 mL de solução salina no grupo controle (Grupo C, n = 8); 3 mL de lidocaína a 2% (Grupo L, n = 8); 3 mL de bupivacaína a 0,5% (Grupo B, n = 8) e 3 mL de tramadol a 5% (Grupo T, n = 8). As medidas de tensão de ruptura, contagem de fibras de colágeno e avaliação histopatológica foram avaliadas nas amostras de tecido retiradas dos ratos. RESULTADOS: A comparação do grupo controle com os grupos onde bupivacaína e lidocaína foram usadas para infiltração da ferida mostrou que nestes últimos a produção de colágeno foi menor e a resistência na tensão de ruptura, enquanto se observou edema mais intenso, vascularização e escores de inflamação significantes (p < 0,0125). Entre o grupo controle e o grupo tramadol não houve diferenças significativas na produção de colágeno, tensão de ruptura e edema, vascularização, e escores de inflamação (p > 0,0125). CONCLUSÃO: Neste estudo, verificou-se que tanto bupivacaína como lidocaína reduziram a produção de colágeno, resistência à ruptura da cicatriz e causaram edema, vascularização e inflamação significantes quando comparadas com o grupo controle. Não houve diferença significativa entre os grupos controle e tramadol para estas variáveis. Os resultados deste estudo experimental preliminar em ratos indicam que o tramadol pode ser utilizado para a anestesia por infiltração em incisões sem efeitos adversos sobre o processo de cicatrização cirúrgica. Estes resultados precisam ser verificados em seres humanos. BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the effects of saline solution, bupivacaine, lidocaine and tramadol infiltration on wound healing in rats. METHOD: Thirty-two male Wistar Albino rats were randomly separated into four groups, receiving 3 mL saline solution in control group (Group C, n = 8), 3 mL of 2% lidocaine in lidocaine group (Group L, n = 8), 3 mL of 0.5% bupivacaine in bupivacaine group (Group B, n = 8), and 3 mL of 5% tramadol in tramadol group (Group T, n = 8). Breaking-strength measurements, collagen bundle counting, and histopathologic evaluation were evaluated in the tissue samples taken from the rats. RESULTS: Comparing the control group with the groups where bupivacaine and lidocaine were used for wound infiltration, collagen production was lower, breaking-strength measurements showed reduced resistance while significantly high edema, vascularity, inflammation scores were found (p < 0.0125). Between the control and the tramadol group there were no significant differences in collagen production, breaking-strength measurements, and edema, vascularity, inflammation scores (p > 0.0125). CONCLUSION: In our study, we found bupivacaine and lidocaine reduced the collagen production, wound breaking strength, and caused significantly high scores for edema, vascularity, and inflammation when compared to the control group. There was no significant difference between the control and the tramadol group. Results of this experimental preliminary study on rats support the idea that tramadol can be used for wound infiltration anesthesia without adverse effect on the surgical healing process. These results need to be verified in humans. JUSTIFICATIVA Y OBJETIVOS: El objetivo de este estudio fue investigar los efectos de la solución salina, de la bupivacaína, lidocaína y de la infiltración de tramadol en la cicatrización de heridas en ratones. MÉTODOS: Treinta y dos ratones Wistar machos albinos fueron ubicados aleatoriamente en cuatro grupos que recibieron 3 mL de solución salina en el grupo control (grupo C, n = 8); 3 mL de lidocaína al 2% (grupo L, n = 8); 3 mL de bupivacaína al 0,5% (grupo B, n = 8) y 3 mL de tramadol al 5% (grupo T, n = 8). Las medidas de tensión de ruptura, conteo de fibras de colágeno y evaluación histopatológica se evaluaron en las muestras de tejido retiradas de los ratones. RESULTADOS: La comparación del grupo control con los grupos donde la bupivacaína y la lidocaína fueron usadas para la infiltración de la herida mostró que en esos últimos, la producción de colágeno fue menor, junto con la resistencia en la tensión de ruptura, mientras se observó un edema más intenso, vascularización y puntajes de inflamación significativos (p < 0,0125). Entre el grupo control y el grupo tramadol no hubo diferencias significativas en la producción de colágeno, tensión de ruptura y edema, vascularización y puntaje de inflamación (p > 0,0125). CONCLUSIÓN: En este estudio, verificamos que tanto la bupivacaína como la lidocaína redujeron la producción de colágeno, la resistencia a la ruptura de la cicatriz y causaron edema, vascularización e inflamación significativas cuando se les comparó con el grupo control. No hubo diferencia significativa entre los grupos control y tramadol para estas variables. Los resultados de este estudio experimental preliminar en ratones indican que el tramadol puede ser utilizado para la anestesia por infiltración en incisiones, sin efectos adversos sobre el proceso de cicatrización quirúrgica. Esos resultados necesitan ser verificados en los seres humanos.

Oxygen free radicals and lipid peroxidation may play significant roles in the progress of injury induced by chronic cerebral hypoperfusion of the central nervous system. Rosiglitazone, a well known activator of PPAR?, has neuroprotective properties in various animal models of acute central nervous system damage. In the present study, we evaluate the possible impact of rosiglitazone on chronic cerebral hypoperfused-rats in regard to the levels of oxidative stress, reduced glutathione, and hippocampal neuronal damage. Chronic cerebral hypoperfusion was generated by permanent ligation of both common carotid arteries of Wistar rats for one month. Animals in treatment group were given rosiglitazone orally at doses of 1.5, 3, or 6 mg/kg per day of the 1 month duration. The treatment significantly lowered the levels of both malondialdehyde and neuronal damage, while elevated the reduced glutathione level markedly. These findings suggest that the beneficial effect of rosiglitazone on hypoperfusion-induced hippocampal neuronal damage might be the result of inhibition of oxidative insult. © 2012 Elsevier Ltd. All rights reserved., SBAG-HD-303, 108S114 National Council for Scientific Research, We have gratefully acknowledged the Research Projects Fund of Turkish Scientific Research Council (TUBITAK) for providing financial support that made the present study possible (the grant # 108S114, SBAG-HD-303 ).

Chronic cerebral hypoperfusion can cause learning and memory impairment and neuronal damage resembling the effects observed in vascular dementia. PPAR-γ agonists were shown to modulate inflammatory response and neuronal death following cerebral ischemia. The present study was designed to evaluate possible neuroprotective effects of rosiglitazone, a PPAR-γ agonist, in rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent bilateral occlusion of the common carotid arteries. Oral administration of rosiglitazone (1.5, 3, and 6 mg/kg/day) or vehicle was carried out for 5 weeks, starting one week before the surgery. Cognitive performance was assessed using the Morris water maze. The density of S100B protein-immunoreactive astrocytes and the OX-42-labeled microglial activation were estimated. Synaptogenesis was also evaluated by the measurement of synaptophysin, the pre-synaptic vesicular protein, level via western blotting technique. Cerebral hypoperfusion for 30 days induced a significant cognitive impairment along with hyperactivation of both microglial and astroglial cells, and reduction of synaptophysin level. Rosiglitazone treatment (3 and 6 mg/kg) not only suppressed the activation of astrocytes and microglia markedly but also alleviated the impairment of memory and increased the synaptophysin level. In conclusion, our results suggest that the chronic administration of rosiglitazone significantly prevents chronic cerebral hypoperfusion-induced brain damage, at least, partly through suppressing glial activation and preserving synaptic plasticity. Thus, it appears that rosiglitazone may be a promising pharmacological agent in the development of therapeutic approaches for the prevention or treatment of cerebrovascular diseases.

The reasons of post-stroke infections are still incompletely understood. Bacterial translocation (BT), the passage of viable microbes across an even anatomically intact intestinal barrier, has been described in many critical illnesses. To date, it has not been studied as a source of infection in an animal stroke model. To address this, a permanent left middle cerebral artery occlusion (MCAO) model in rats was used. After 24, 48, and 72 hours (h), sham and experimental groups were sacrificed and samples were taken for BT. Similarity between bacteria detected in tissues (blood, mesenteric lymph node, liver, spleen, and lung) and intestinal microflora was shown with phenotypic methods and antibiotyping. Possible ileum tissue injuries were shown by histopathologic examination (including morphometric analysis). Although there was no bacterial proliferation in the sham groups, 55.5%, 45.4%, and 30% bacterial proliferation was detected in MCAO groups at postoperative hour 24, 48, and 72, respectively. In MCAO groups the bacterial proliferation in tissues and ileum tissue injury scores were higher over time compared to sham groups (p0.05). Our findings support the view that stroke, itself leads to mucosal damage and bacterial translocation (Tab. 5, Fig. 2, Ref. 27).

Aims: Considering the implications that arose from several recent experimental studies using recombinant human erythropoietin in rodents, erythropoietin has been regarded as a pharmacological preconditioning agent. The purpose of the present study was to evaluate whether erythropoietin has a preconditioning effect against ischemia and reperfusion injury in the small intestine of the rat. Main methods: Intestinal ischemia was induced in male Wistar rats by clamping the superior mesenteric artery for 30 min, followed by reperfusion for 180 min. Recombinant human erythropoietin (1000 or 3000 U/kg) or vehicle was administered intraperitoneally 24 h prior to ischemia. After collection of ileal tissue, evaluation of damage was based on measurements of the accumulation of polymorphonuclear neutrophils by technetium-99m-labeled leukocyte uptake, content of malondialdehyde, reduced glutathione, contractile responses to agonists, and an evaluation of histopathological features in intestinal tissue. Key findings: Treatment with erythropoietin 24 h before ischemia significantly reduced the tissue content of malondialdehyde and increased that of reduced glutathione. Pretreatment also significantly suppressed leukocyte infiltration into the postischemic tissue, as evidenced by the lower content of myeloperoxidase and technetium-99m-labeled leukocytes. Physiological and histopathological improvements were also significant with the rHuEpo treatment. Significance: Results of the present study indicate that rHuEpo is an effective preconditioning agent in ischemic injury of the small intestine. Protection provided by recombinant human erythropoietin is closely related to the inhibition of oxidative stress and leukocyte infiltration, which might be among the possible protective mechanisms of erythropoietin in intestinal ischemia and reperfusion. © 2009 Elsevier Inc. All rights reserved.

OBJECTIVES: Studies have shown that nitric oxide (NO) may play a major role in sustaining mucosal integrity; however, NO has been also implicated in the pathogenesis of ischemia/reperfusion (I/R)-related tissue injury. We investigated the effects of L-arginine and N-nitro L-arginine methyl ester (L-NAME) on the acetylcholine-induced contractile response of ileum and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Histopathological changes were also evaluated in ileal preparations. MATERIALS AND METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 hours). Four groups were designed: sham-operated control; I/R; I/R and L-arginine pretreatment; and I/R and L-NAME pretreatment. After reperfusion, ileum specimens were collected to determine the parameters mentioned above. RESULTS: Following reperfusion, a significant decrease in acetylcholine-induced contractile response, an increase in lipid peroxidation, a decrease in GSH content, and mucosal damage of the ileal preparations were observed. We showed that decreased contractility, increased lipid peroxidation, and reduced GSH content have been reversed by L-arginine but not by L-NAME. Mucosal injury was significantly lowered in the L-arginine group. CONCLUSIONS: Treatment with L-arginine exerted a protective effect in intestinal I/R injury, which was mediated in part by regulating MDA and GSH levels, consequently ameliorating impaired contractile response and mucosal injury. © 2008 Lippincott Williams & Wilkins, Inc.

WOS: 000243916200008, PubMed: 17278219, AIM: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury. METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N-6-cyclo- pentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase, malondialdehyde, and reduced glutathione levels were measured. RESULTS: Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist. CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content. (c) 2007 The WJG Press. All rights reserved.

Erythropoietin exerts hematopoietic effects by stimulating proliferation of early erythroid precursors. Nonhematopoietic effects of erythropoietin have also been shown. It may act as a new angiogenic factor in wound healing. This study aimed to investigate the effect of systemic administration of recombinant human erythropoietin on wound healing in mice. Dorsal incisional wounds were performed in mice, which were then divided into two groups; a group treated for 7 days with recombinant human erythropoietin, and a control group. Sacrificing animals on day 7, the wound tissues were collected for analysis of wound breaking strength, malondialdehyde, a marker of lipid peroxidation, hydroxyproline, an index of reparative collagen deposition, reduced glutathione levels, and for histological evaluation. The immunohistochemical determination of vascular endothelial growth factor (VEGF) which is believed to be the most prevalent angiogenic factor throughout the skin repair process, was also studied. The treatment significantly increased wound breaking strength by decreasing malondialdehyde and increasing hydroxyproline levels on day 7 after wounding. No statistically meaningful change was observed in reduced glutathione content. VEGF was immunostained significantly more on wound tissue of treated animals compared to the control group. Recombinant human erythropoietin treatment may be effective in wound healing due to inhibition of lipid peroxidation, deposition of collagen, and VEGF expression in wound area. Copyright © Taylor & Francis Group, LLC.