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    Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment
    (Springer, 2006) Cigremis, Yilmaz; Parlakpinar, Hakan; Polat, Alaadin; Colak, Cemil; Ozturk, Feral; Sahna, Engin; Ermis, Necip
    Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.
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    The effects of nitric oxide on extensive epidural fibrosis after laminectomy in rats: a preliminary study
    (İnönü Üniversitesi Sağlık Bilimleri Dergisi, 2016) Aladağ, Murat; Türköz, Yusuf; Sahna, Engin; Cengiz, Nureddin; Parlakpınar, Hakan; Cihan, Faruk; Gül, Mehmet
    Amaç: Laminektomi ve/veya diskektomi sonrası, tüm önleyici işlemlere rağmen, hastaların bir alt grubunda aşırı epidural fibrozis gelişmektedir. Bizim hipotezimiz, laminektomi sonrası aşırı fibrosis gelişen hastalarda yara iyileşmesinin geç safhasında nitrik oksit (NO) üretiminin arjinaz tarafından inhibisyonunda bir defektin olduğu şeklindedir. Amacımız, bir hayvan laminektomi modelinde aşırı fibrozis gelişmesi üzerinde NO ve arjinaz’ın etkisini araştırmaktır. Gereç ve Yöntem: Bu çalışmada, 50 erkek wistar rat beş gruba ayrıldı; tümüne lomber laminektomi yapıldı. Laminektomi sonrası 3. ve 12. gün arasında, 1. gruba (kontrol) serum fizyolojik, 2. gruba; indüklenebilir nitrik oksit sentazı (iNOS) uyarmak üzere lipopolisakkarit (LPS), 3. gruba LPS ve L-arginin (NOS substratı), 4. gruba gliseril trinitrat (NO donörü) ve 5. gruba L-valine (arjinaz inhibitörü) intraperitonal olarak verildi. Sonuçlar: Hayvanların tümü 12. gün sakrifiye edildi ve hayvanların tümünde epidural fibrozis gross ve histolojik inceleme ile değerlendirildi. 2. grupta yara iyileşmesi ve fibrozis zayıf iken, 3'üncü grupta hafif derecede kompresyon yapan bir epidural fibrozis vardı. 4. ve 5'inci gruplarda ise ciddi derecede kompresyon yapan bir epidural fibrozis vardı. Tartışma: iNOS inhibe edilerek NO üretiminin azalması ve L-arjinin’in büyük oranda arjinaz tarafından kullanılması, yara iyileşmesinin geç dönemindeki tamir ve yenilenme işlemini etkileyen en önemli faktörler olduğu kanaatindeyiz. Anahtar Kelimeler: Rat, Laminektomi, Nitrik Oksit, Arjinaz, Epidural Fibrozis, Yara Iyileşmesi.
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    Melatonin protects myocardium from ischemia-reperfusion injury in hypertensive rats: Role of myeloperoxidase activity
    (Taylor & Francis Inc, 2008) Sahna, Engin; Deniz, Esra; Bay-Karabulut, Aysun; Burma, Oktay
    Increased levels of reactive oxygen species, alterations in nitric oxide synthesis, and increased migration of neutrophils to the ischemic tissue play an important role in the pathophysiology of myocardial ischemia-reperfusion (IR) injury. In this study, we have evaluated the effects of melatonin on myeloperoxidase (MPO) activity, tissue glutathione (GSH), lipid peroxidation levels, and blood pressure in L-NAME-induced hypertensive rats with or without IR. NOS inhibitor L-NAME was administrated before inducing cardiac ischemia for 15 days intraperitoneally. For the cardiac ischemia, the left coronary artery was ligated for 30 min, and reperfusion was performed for 120 min after the ischemia. L-NAME treatment in non-ischemic animals increased blood pressure and lipid peroxidation, and decreased glutathione level in myocardial tissue significantly as compared with non-L-NAME-treated animals. Melatonin reversed L-NAME-induced blood pressure elevation and oxidative changes. Cardiac IR increased MDA levels and MPO activity and decreased GSH levels as compared with non-ischemic animals. L-NAME treatment did not change in IR-induced MDA and GSH levels as compared with ischemic control animals. However, MPO activity was significantly higher than control ischemic animals. MDA levels and MPO activity resulting from ischemic injury in melatonin-treated animals were significantly less than L-NAME-treated animals. Taken togetherthe ischemic and non-ischemic control and melatonin-treated animalsthis study shows that neutrophil migration plays an important role on the development of ischemic injury in hypertensive rats.
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    Morphological Changes and Vascular Reactivity of Rat Thoracic Aorta Twelve Months After Pinealectomy
    (Ortadogu Ad Pres & Publ Co, 2010) Kurcer, Zehra; Ozturk, Feral; Sahna, Engin; Kurus, Meltem; Olmez, Ercument
    Objective: Melatonin, a hormone produced by the pineal gland, has been suggested to protect against development of hypertension and atherosclerosis. In this study, the effects of long-term melatonin deficiency for twelve months after pinealectomy on the alpha-adrenergic-contractions induced by phenylephrine, endothelium-dependent relaxation responses to acetylcholine and the morphological changes in the rat thoracic aorta were studied. Material and Metods: Rats were pinealectomized twelve months before the beginning of the vasomotor studies. Rings of arteries were mounted in isolated tissue baths for the measurements of isometric contractile force. The contractile responses to phenylephrine and endothelium-dependent relaxation responses to acetylcholine in the vessels were evaluated. Endothelial function was evaluated by vascular relaxation to acetylcholine. Histological examinations demonstrated the alterations of tunica media in the vessels of pinealectomized rats. Results: Thick and thin areas were observed in the transverse sections of vessels and the ratio of the widest media thickness to the narrowest was found significantly increased in pinealectomized group (2.85 +/- 056) when compared to the control group (1.65 +/- 0.10). In addition, alpha-smooth muscle actin and elastic lamellae staining of the media were attenuated in pinealectomized rats. Although contractile responses of vessels to phenylephrine in pinealectomized rats were lower than control group, significant difference was found for only one concentration (3x 10-8 mol l-1) of phenylephrine. There was no difference between the relaxation responses to acetylcholine in pinealectomized and control groups. Conclusion: These results show that long-term melatonin deficiency may cause some morphological changes in the tunics media of vessels. However, the function of endothelium and vascular responsiveness to proportional to-adrenergic stimulus seem to be mostly protected.
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    Role of Propolis on Tyrosine Hydroxylase Activity and Blood Pressure in Nitric Oxide Synthase-Inhibited Hypertensive Rats
    (Taylor & Francis Inc, 2012) Gogebakan, Ayse; Talas, Zeliha Selamoglu; Ozdemir, Ilknur; Sahna, Engin
    Reduction in the synthesis or bioavailability of nitric oxide plays a significant role in the development of hypertension. Propolis is a resinous product collected by honeybees from various plant sources. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamines. The aim of this study was to examine the effect of propolis on blood pressure (BP), TH, and total RNA levels in the adrenal medulla, heart, and hypothalamus tissues in chronic nitric oxide synthase (NOS)-inhibited rats by N-w-nitro-L-arginine methyl ester (L-NAME). Rats received NOS inhibitor (L-NAME) for 15 days to produce hypertension and propolis for the last 5 days. TH activity and total RNA levels significantly increased in adrenal medulla, heart, and hypothalamus tissues in L-NAME-treated groups (P < .05). TH activity and total RNA levels of L-NAME+propolis-treated rats reduced (P < .05) compared with L-NAME-treated groups. TH activity in propolis-treated rats was reduced to the control values. L-NAME led to a significant increase in BP compared with the control group. Propolis administration to L-NAME-treated rats reduced BP but this was not statistically significant compared to L-NAME-treated groups. These results suggest that propolis decreases TH activity in NOS-inhibited hypertensive rats and thereby may modulate the synthesis of catecholamine and BP.