The Effects of Irisin on N?-Nitro-L-arginine Methyl Ester Hydrochloride-Induced Hypertension in Rats

Background: The cause of about 95% of hypertension, an important public health problem, is unknown. Intensive studies are underway to understand the physiopathology of hypertension. Irisin, a newly discovered hormone, has been reported to dilate vascular smooth muscle and lower blood pressure acutely. Aims: To investigate the effects of chronic irisin treatment on blood pressure and renal functions in a hypertension model established by nitric oxide synthase inhibition by treatment with N?-nitro-L-arginine methyl ester hydrochloride. Study Design: Animal experimentation. Methods: Male Sprague?Dawley rats were divided into four groups (n=8). Control and irisin groups received an intravenous saline injection, hypertension and hypertension + irisin (hypertension + irisin) groups received 1.5 mg/100 g N?-nitro-L-arginine methyl ester hydrochloride. N?-nitro-L-arginine methyl ester hydrochloride (150 mg/L) was added to the drinking water of rats in groups hypertension and hypertension + irisin for three weeks. In the second week of the experiment, irisin (50 nmol/day) was given to rats in groups irisin and hypertension + irisin, and saline was administered to rats in groups control and hypertension for two weeks through subcutaneously placed osmotic minipumps. Blood pressure was measured by the tail-cuff plethysmography method. On the twenty-first day of the experiment, 24-hour urine, blood, and both kidneys of the rats were collected. Results: The hypertension group had elevated systolic, diastolic, and mean arterial blood pressure values compared with the control group, with decreased glutathione levels in tissue and serum, but an increase in serum oxidized glutathione level (p<0.05). Histopathologically, increased tubular injury, cast formation, glomerular sclerosis, and peritubular fibrosis levels were observed (p<0.05). Irisin treatment did not cause any significant change in blood pressure, renal functions, and injury scores. However, renal nitric oxide levels significantly increased, and endothelial nitric oxide synthase immunoreactivity was determined to be reduced (p<0.05). Conclusion: Treatment with chronic irisin at a physiological dose does not reduce blood pressure in an experimental model of hypertension. In different models of experimental hypertension, the effects of irisin administration at different doses and at different periods should be thoroughly investigated

Investigation of the possible role of luteolin in breast cancer

Yüksek Lisans TeziBu çalışmanın amacı in vivo Erhlich asit meme tümör modelinde, serum ve doku örneklerinde luteolinin arginaz enzim aktivitesi, ornitin ve poliamin (putresin, spermidin, spermin) düzeyleri üzerine etkilerini incelemektir. Dişi balb/c fareler, sağlıklı kontrol, sağlıklı tedavi, tümör kontrol, tümör tedavi 1 ve tümör tedavi 2 olmak üzere gruplara ayrıldı. Farelerin sol bacak iç bölgesine subkutan olarak 0.2 mL Ehrlich asit tümör hücresi enjekte edildi. Luteolin 5 mg/kg/gün ve 10 mg/kg/gün dozlarında 12 gün boyunca sağlıklı tedavi, tümör tedavi 1 ve tümör tedavi 2 gruplarına intraperitoneal olarak verildi. Luteolin hidroksile flavinoid yapısında, güçlü antioksidan, antiinflamatuvar, antikanserojen aktivitelere sahip bir flavonoiddir. Luteolin, çeşitli kanser hücrelerinin hücre sağ kalım yolaklarını baskılayarak ve apoptoz yolaklarını uyararak, tümör hücrelerinin ölümüne neden olmakla birlikte sitotoksik tedaviye duyarlı hale gelmelerini de sağlamaktadır. Daha önce yapılan birçok çalışmayı destekleyerek, sağlıklı hayvanlara tümör implantasyonumuz istatistiksel olarak artmış serum arginaz ve poliamin düzeyleri ile sonuçlanarak, bu artmış üretimin sorumlusunun tümör hücreleri olduğunu gösterdi. (p<0.05). Luteolin tedavisi ise serumdaki arginaz ve poliamin yükselişini ortadan kaldırdı (p<0.05).Tümör implantlı hayvanların serumlarındaki yükselen arginaz ve poliamin düzeyleri luteolin tedavisi ile azalırken, dokulardaki ölçümlerimiz bu parametrelerin tedavi ile arttığını göstermiştir. Sonuçlarımız dokuda artan bu arginaz ve poliamin düzeylerinin luteolinin kullanılan tümör modeli üzerindeki agonist östrojenik etkisinden olabileceğini ve tümörlü dokuda artarken serumda azalan parametrelerde tümörlü dokudan poliamin effluksunun luteolinin plazma membran poliamin transportörleri üzerinde oluşturduğu baskılayıcı etkiden meydana gelebileceğini vurgulamıştır.abstractThe aim of this study is to investigate the effects of luteolin treatment on enzymatic activity of arginase, ornithine and polyamine levels (putrescine, spermidine spermine) in serum and cancer tissues in in vivo Erhlich ascites breast cancer model. Balb/c female mice were divided randomly into following groups: healthy control, healthy treatment, cancer control, treatment 1 and treatment 2. 0.2 mL Ehrlich ascites tumor cells was inoculated subcutaneously to medial part of left hind leg. Healthy treatment and treatment 1 groups, and the treatment group 2 were given 5 mg/kg and 10 mg/kg dose of luteolin, intraperitoneally, for a 12 days period, respectively. Luteolin has a hydroxylated flavonoid structure and shows potent antioxidant, anti-inflammatory, and anticarcinogenic properties. Luteolin not only leads to cell death in various tumors by suppressing cell survival pathways and stimulating apoptotic pathways, but also sensitize them to cytotoxic therapy. Supporting various previous studies, tumor implantation to healthy mice resulted in statistically significant elevation of serum arginase and polyamine levels (p<0.05) indicating the tumor cells as the main source of this production. Furthermore, luteolin treatment abolished this increase in serum arginase and polyamine levels (p<0.05). Tissue measurements of arginase and polyamine levels indicated that luteolin treatment resulted with an increase in these parameters of tumor tissue while the serum levels of them showed a significant decrease. Our results revealed that increased tissue arginase and polyamine levels might be related with estrogenic agonistic effect of luteolin on utilized tumor model in this experiment; and decreased serum levels of these parameters while there is a significant increase of them in tissue levels might be a result of a suppression of polyamine efflux from the tumor tissue by inhibitory effect of luteolin on plasma membrane polyamine transporters

Investigation of the effects of lycopene on experimentally hypertension-induced rats

Hipertansiyon, prevalansının yüksek olması, kardiyovasküler ölümlerin başında gelmesi sebebiyle önemli bir halk sağlığı sorunudur. Domates ve ürünleriyle vücuda alınan majör karotenoidlerden biri olan likopenin, antioksidan ve kardiyovasküler hastalıklara karşı koruyucu olduğu bildirilmiştir. Çalışmamızda likopen tedavisinin N?-Nitro-L-arginine metil ester hidroklorid (L-NAME) ile oluşturulmuş hipertansiyon gelişimindeki rolünü ve böbrek fonksiyonları üzerindeki etkilerini araştırmayı amaçladık. Çalışmamızda 32 adet erkek Spraque-Dawley sıçan Kontrol (K), Kontrol + Likopen (K+L), Hipertansiyon (HT) ve Hipertansiyon + Likopen (HT+L) olmak üzere 4 gruba ayrıldı. K ve K+L gruplarına fizyolojik serum, HT ve HT+L gruplarına 15 mg/kg L-NAME intravenöz ve 150 mg/L dozunda (L-NAME) içme sularında 3 hafta boyunca verildi. K+L ve HT+L gruplarına 10 mg/kg/gün dozunda likopen, K ve HT gruplarına ise likopenin çözücüsü olan mısır yağı 1 ml/kg dozunda 2 hafta boyunca gavaj yolu ile verildi. Her hafta tail-cuff pletismografisi yöntemi ile kan basıncı ölçümü yapıldı. Deneyin 21. gününde sıçanların 24 saatlik idrarları toplandıktan sonra anestezi altında kan ve böbrekleri alınarak ötenazi uygulandı. Kontrol grubuna göre Kontrol+Likopen grubunda likopen uygulamasının; serum sodyum, üre, kreatinin, kopeptin, anjiyotensin dönüştürücü enzim ve mikroalbumin düzeylerinin azaldığı, kreatinin klirensinin arttığı ve fraksiyonel sodyum atılımının azaldığı saptandı (p<0,05). Hipertansiyon grubunda Kontrol grubuna kıyasla sistolik, diyastolik ve ortalama kan basıncı, serum aldosteron, anjiyotensin 2 düzeylerinin arttığı, likopen tedavisinin kan basıncı üzerinde anlamlı bir düşüşe neden olduğu saptandı (p<0,05). Bulgularımız; likopenin L-NAME ile oluşturulan hipertansiyon modelinde kan basıncı üzerinde potansiyel düşürücü etkilerine rağmen, likopenin dozu, veriliş yolu ve sürelerinde yapılacak düzenlemeler ile daha kapsamlı araştırılması gerektiğini düşünmekteyiz.Hypertension is an important public health problem due to the high prevalence of cardiovascular deaths. Lycopene, one of the major carotenoids taken with the tomato and tomato products, has been reported to protect against antioxidants and cardiovascular diseases. We aimed to investigate the role of lycopene treatment in the development of hypertension and its effects on renal function in our study. We aimed to investigate the role of lycopene treatment in the development of hypertension induced by N?-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and its effects on renal function. In our study, 32 male Spraque-Dawley rats were divided into 4 groups as Control (C), Control + Lycopene (C+L), Hypertension (HT) and Hypertension + Lycopene (HT+L). HT and HT+L groups were given 15 mg / kg N?-Nitro-L-arginine methyl ester hydrochloride (L-NAME) intravenously, followed by 150 mg/L L-NAME in the drinking water for 3 weeks to induce experimental hypertension; C and C + L groups were given physiological serum intravenously. Rats in groups 2 and 4 were given lycopene at a dose of 10 mg/kg/day via gavage and groups 1 and 3 were also given 1 ml/kg/day corn oil which was a vehicle for lycopene for 2 weeks. Blood pressure measurements by the tail-cuff plethysmography performed every week. The 24-hour urine, blood and both kidneys of the rats were collected on the 21st day of the experiment. Comparing to C group, serum sodium, urea, creatinine, copeptin, angiotensin converting enzyme and microalbumin levels and fractional sodium excretion decreased, and creatine clearance increased in C + L group (p<0.05). Systolic, diastolic and mean arterial blood pressure values, serum aldosterone, angiotensin 2 levels were increased in hypertension group compared to control group, and lycopene treatment caused a significant decrease blood pressure (p<0,05). Our findings; we success that lycopene should be further investigated in the model of hypertension induced by L-NAME, with the regulations to be made on the way of dosing, administration and duration of lycopene, despite the potential effects on blood pressure

Investigation of Kisspeptin Role in Experimental Kidney Ischemia/Reperfusion Injury

Introduction: Kisspeptin is biologically active peptide encoded by the KISS1 gene that is structurally found in the kidney tubule, collecting duct and vein smooth muscle cells.  Aim: We aimed to investigate the role of kisspeptin in kidney function and renal pathophysiology in experimental kidney ischemia/reperfusion (I/R) injury.  Materials and methods: Male Spraque-Dawley rats were divided into control and I/R groups (n=8). Both kidney vessels of I/R group rats were clamped and subjected to ischemia for 60 minutes and reperfusion for 48 hours. After the reperfusion period blood samples and kidney tissue were collected under anesthesia.  Results: Levels of urea, creatinine (p<0.01) in serum, Kim-1 in urine (p<0.05) were increased, creatinine clearance, aldosterone and ANG II levels in serum were decreased in the I/R group compared with the Control group (p<0.05). Kidney kisspeptin levels decreased and urine kisspeptin levels increased (p<0.05).  Conclusions: The present study has shown that the levels of kisspeptin change in kidney damage and thus the kisspeptin may play a role in the regulation of renal function and in the pathophysiology of acute kidney injury