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Öğe Adrenomedullin administration alters vascular endothelial growth factor levels in rats in cold stress(Chulalongkorn Univ, Fac Med, 2010) Yildirim, Nuran Cikcikoglu; Yurekli, MuhittinBackground: Many endogenous peptides play important regulatory roles in angiogenesis by modulating endothelial cell behavior. Adrenomedullin (AdM) is one of such factors. Angiogenesis and vascular endothelial growth factor (VEGF) are indistinguishable. Exposure to cold environment stimulates capillary angiogenesis. Objectives: Examine the effect of the bioactive peptide AdM on VEGF levels in rat liver, lung, brain, and heart tissues after cold stress treatment. Methods: Male wistar rats were divided into four groups as control, AdM treatment, cold stress and AdM+cold stress treated groups. In AdM-treated group, animals received intraperitoneal injection of AdM (2000 ng/kg body weight) once a day during a week. For the cold stress exposure, the rats were kept in separate cages at 10 degrees C for a week. Results: The administration of AdM increased VEGF levels in all tissues in cold exposed rats. Conclusion: AdM may be a major regulatory factor in angiogenesis by modulating VEGF levels that is closely associated with cold exposure-related metabolic stimulation.Öğe Adrenomedullin has a role in angiogenic effects of resveratrol in adipose tissues of obese female rats(Springer, 2020) Culum, Ayse Asiye; Yurekli, MuhittinObesity is a complex, chronic disease that arises according to the interaction between genetic and environmental factors. The expansion and growth of white adipose tissue (WAT) could be related to angiogenesis. Resveratrol and adrenomedullin (AdM) were used for the inhibition of angiogenesis in metabolically passive WAT for inhibiting the expansion of this tissue, and the activation of angiogenesis in metabolically active brown adipose tissue (BAT) for increasing daily energy consumption as a way of reducing obesity. Rats were divided into eight groups. Four obese groups were fed with a high-fat diet containing 60% fat as energy for three months. After obtaining obesity, 2.5 nmol/kg AdM and 10 mg/kg resveratrol were treated to experiment groups intraperitoneally (i.p.) every other day for four weeks. AdM and vascular endothelial growth factor A (VEGF-A) mRNA levels were detected with semi-quantitative PCR; protein levels were detected with Western Blotting. AdM and resveratrol are multifactorial molecules, thus, this study has revealed a few novel evidence. The results were distinct in the group and treatment levels. The results showed that resveratrol has a role in angiogenesis in obesity and contributed to AdM production. It is observed that AdM has regulated its expression and increased the effect of resveratrol in WAT. AdM and VEGF-A gene expressions could not be detected in BAT; however, it is suggested that resveratrol may have a pro-angiogenic effect in BAT of obese rats according to the protein levels. AdM also has regulated VEGF-A level according to the metabolic situation of the organism.Öğe Adrenomedullin Reduces Antioxidant Defense System and Enhances Kidney Tissue Damage in Cadmium and Lead Exposed Rats(Wiley, 2009) Yurekli, Muhittin; Esrefoglu, M.; Dogru, M. Ilker; Dogru, Arzu; Gul, M.; Whidden, M.Adrenomedullin (AdM) is synthesized and secreted by a number of cells and tissue. AdM is a potent vasodilator but it is also considered a neuromodulator, an angiogenic factor, and a hormone regulator. AdM possess antiapoptotic, antioxidant, and antimicrobial properties. Heavy metals such as cadmium and lead are found widely in the environment and they have important biological functions. Lead (Pb) and cadmium (Cd) can accumulate in the lungs, liver, bone, and kidneys and cause serious organ damage. In the present study, we investigated the effect of AdM, Pb + AdM, and Cd + AdM treatments on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as the level of malondialdehyde (MDA) in the kidney. Heavy metal accumulation was determined in kidney with and without AdM infusion and kidney damage was evaluated by light and electron microscopy. Increased heavy metal accumulation was observed in the heavy metal and AdM treated groups. SOD, CAT, GSH-Px activities, and MDA levels were significantly different in the treatment groups when compared with the control group. Tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles were observed in the kidney following treatment. Therefore, AdM infusion has no beneficial and/or compensatory role in cadmium and lead toxicity in the kidney. We conclude that heavy metal accumulation in the kidney in conjunction with AdM infusion is cytotoxic despite the known beneficial effects of adrenomedullin. (C) 2008 Wiley Periodicals, Inc. Environ Toxicol 24: 279-286, 2009.Öğe Circulating adrenomedullin levels in ankylosing spondylitis and Familial Mediterranean Fever(Elsevier France-Editions Scientifiques Medicales Elsevier, 2008) Ureten, Kemal; Ozbek, Mustafa; Ozturk, Mehmet Akif; Dogru, Ilker; Dogru, Arzu; Yurekli, Muhittin; Karakurt, FeridunIntroduction: Adrenomedullin (AM) is a 52-amino acid peptide with vasorelaxant properties. Apart from its roles on vascular tonus, AM can also contribute to inflammatory events. Plasma AM levels were elevated in connective tissue diseases and vasculitic disorders. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine initiating in the sacroiliac joints. Familial Mediterranean Fever (FMF) is a hereditary disorder characterized by self-limiting acute attacks of fever and the presence of sustained subclinical inflammation in the attack-free periods. In this study, we investigated plasma AM levels in patients with AS and patients with FMF. Methods: Twenty AS patients with active disease manifestations (mean age: 41.6 +/- 10.9 years, female/male: 7/13), 28 FMF patients with acute attack (mean age: 27.4 +/- 10.7 years, female/male: 17/11), and 26 healthy controls (mean age: 39.9 +/- 5.5 years, female/male: 16/10) were enrolled in this study. AM levels were also measured in 11 FMF patients 2 months after the cessation of their attacks. AM levels of those 11 patients during their FMF attacks and attack-free periods were also compared. Results: Median plasma AM levels were 23.86 (17.24-40.09) pmol/mL, 27.33 (17.24-38.52) pmol/mL, and 26.11 (17.05-37.42) pmol/mL in AS patients, FMF patients with acute attack, and healthy controls, respectively (p > 0.05). AM levels were also similar in the attack-free periods of FMF patients [26.35 (24.35-34.14) pmol/mL]. There was no correlation between plasma AM levels and C-reactive protein, or between plasma AM levels and erythrocyte sedimentation rate. Conclusions: AM does not seem to have any role in the pathogenesis of AS and FMF. Previous reports of elevated levels of AM in connective tissue disorders and vasculitic diseases are probably disease specific, and AM does not seem to be a common component of inflammatory rheumatic disorders. (C) 2008 Elsevier Masson SAS. All rights reserved.Öğe The effect of adrenomedullin on rats exposed to lead(Wiley, 2008) Dogru, Mehmet Ker; Dogru, Arzu Kocagun; Gul, Mehmet; Esrefoglu, Mukaddes; Yurekli, Muhittin; Erdogan, Selim; Ates, BurhanAdrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The antioxidative properties of AdM have been reported recently. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by stressors. Lead, commonly detected in air, soil, water and food, is a major source of oxidative stress. The effect of AdM in the liver of rats exposed to lead was investigated. Twenty-four female Wistar rats were divided into four groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead + adrenomedullin (Ph + AdM) group. In the Pb-treated groups, the animals were exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1) body weight) in the third week of lead treatment for I week. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the level of malondialdehyde (NIDA) were determined in the liver of rats. Histological changes in the liver were examined by light and electron microscopy as well. The NIDA levels were increased significantly in the Pb-treated groups, but in the Ph + AdM group the NIDA levels were decreased significantly when compared with the Ph group. AdM reduced hepatic damage in the Pb + AdM group, but the difference in the total histopathological scores between the Pb and Ph + AdM groups was not significant. When the results are taken together, it can be concluded that AdM may have protective or compensating effects in lead toxicity. Copyright (c) 2007 John Wiley & Sons, Ltd.Öğe THE EFFECT OF BOTULINUM TOXIN A ON LEPTIN, GHRELIN, INSULIN, GLUCAGON, AND OXIDATIVE STRESS IN DIET-INDUCED OBESITY RAT MODEL(Springer, 2023) Cinar, Saffet; Guler, Sertac Ata; Simsek, Turgay; Yurekli, Muhittin; Posteki, Gokhan; Utkan, Nihat Zafer; Canturk, Nuh Zafer[Abstract Not Available]Öğe EFFECT OF PHYSICAL ACTIVITY ON PLASMA ADRENOMEDULLIN CONCENTRATION AND ITS RELATIONSHIP WITH NITRIC OXIDE IN ATHLETES(Aves, 2012) Dursun, Nurcan; Yurekli, Muhittin; Ozdogan, KalenderObjective: The aim of this study was to determine whether regular physical activity or acute exercise influenced plasma adrenomedullin (AM) concentration and whether it was related to gender, blood pressure and nitric oxide (NO) production. Material and Methods: Sixty healthy students participated in this study. They were divided into two groups. The first group consisted of 30 students, 16 female, 14 male athletes carrying out regular exercise. The second group was made up of 15 females, 15 males nonathletes. All students submitted to a cycle exercise test until volitional exhaustion. Heart rate (HR), blood pressure, maximal oxygen uptake (VO2 max) and carbon dioxide production (VCO2) were measured continously. Before starting, at the 1st min and at the 30th min of exercise, venous blood samples were taken to determine AM and NO production. Results: AM in the female and male athletes were significantly higher than in the female and male non-athletes. The plasma AM concentration in female athletes was found be significantly higher than in male athletes. Acute exercise did not affect AM concentration in subjects. We did not find any relationship between AM/BMI (Body mass index) and other variables such as systolic, diastolic pressure, heart rate, VO2 max and VCO2 but there was a negative relationship with NO production. Conclusion: The present data suggest that an increase in AM during prolonged physical activity may be a compensatory mechanism against further elevation of blood pressure.Öğe The Effects and Angiogenic Features of Adrenomedullin in Obese Rats(Federation Amer Soc Exp Biol, 2015) Yurekli, Muhittin; Culum, Ayse[Abstract Not Available]Öğe The effects of adrenomedullin and methylated-adrenomedullin treatments on some antioxidative enzyme activities and malondialdehyde levels in rat liver(Federation Amer Soc Exp Biol, 2009) Yurekli, Muhittin; Esrefoglu, Mukaddes; Tumer, Nihal; Dogru, Ilker Mehmet; Gul, Mehmet; Dogru, Arzu; Yyldyrym, Nuran[Abstract Not Available]Öğe Plasma adrenomedullin, serum nitric oxide and leptin levels in obese children(Karger, 2006) Bideci, Aysun; Erbas, F. Baris; Camurdan, Orhun; Yesilkaya, Ediz; Demirel, Fatma; Yurekli, Muhittin; Erbas, Deniz[Abstract Not Available]Öğe THE ROLE OF METHYLATED ADRENOMEDULLIN IN ENZYMATIC ANTIOXIDANT DEFENSE RESPONSE TO COLD STRESS(Parlar Scientific Publications (P S P), 2010) Yildirim, Nuran Cikcikoglu; Yurekli, MuhittinThe aim of our study was to investigate the effects of methylated adrenomedullin (met-AdM) on some antioxidant enzymes, such as catalase (CAT), glutathione peroxidase (GSH-P-X) and superoxide dismutase (SOD) in rat kidney and heart tissues after cold stress treatment. Male Wistar rats were divided into 4 groups (control, met-AdM, cold stress and cold stress + met-AdM treatments). The rats were kept at room temperature, exposed to a 16/8-hours light/dark cycle. The rats were maintained at ad libitum (free) feeding habit. In met-AdM treated group, animals received intraperitoneal injection of met-AdM (2 mg/g body weight) once a day during a week. For the cold stress exposure, the rats were kept in separate cages at 10 degrees C for a week. Control group rats were kept at laboratory conditions. CAT, GSH-P-X and SOD enzyme activities were investigated in kidney and heart tissues. In kidney tissue compared to control, CAT and GSH-P-X enzyme activity was decreased but SOD was increased in met-AdM-treated group. In met-AdM+cold stress group, only the SOD enzyme activity was significantly increased but CAT and GSH-P-X decreased. SOD and GSH-P-X enzyme activities were increased by cold stress but CAT was decreased in kidney. In heart tissue, CAT and GSH-P-X activities were decreased but SOD was increased in met-AdM-treated group compared to control. All enzyme activities were decreased in met-AdM+cold stress group as well as by cold stress in heart, with regard to control. Cold stress can disrupt the balance in an oxidant/antioxidant system and cause oxidative damage to kidney and heart tissues by altering the enzymatic and non-enzymatic antioxidant status. We can suggest that met-AdM has possible roles in regulation of stress but we need further studies revealing responses of met-AdM in different tissues.Öğe Stress-Induced Changes in Tyrosine Hyroxylase Enzyme Activity and Adrenomedullin Levels in Rat Hypothalamus, Adrenal Medulla and Heart Tissues(Academic Journals Inc, 2010) Yildirim, Nuran Cikcikoglu; Yurekli, MuhittinIn this study, it was aimed to investigate the effects of chronic cold stress on adrenomedullin levels and tyrosine hydroxylase enzyme activities in some rat tissues. In this study, 12 female Sprague Dawley rats weighing 200 to 250 g were used. Rats were housed under diurnal lighting conditions (12-12 h) with free access to food and water. For this study, rats were divided into two groups, namely control group and cold stress treated group. Adrenomedullin levels were measured by high performance liquid chromatography. Tyrosine hydroxylase enzyme activities was spectrometrically measured. Tyrosine hydroxylase activity was found to be increased significantly (p<0.05) in adrenal medulla, hypothalamus and heart tissues depending on cold stress treatment. Adrenomedullin levels were determined to be decreased in the cold stress treatment group. The differences of between control and cold stress treatment groups were significant (p<0.05). The results suggested that adrenomedullin may play a possible role in adaptation to stress. Exposure to cold increases the synthesis and release of catecholamines. Tyrosine hydroxylase is the rate limiting step in the biosynthesis of catecholamines for this reason cold stress increased tyrosine hyroxylase enzyme activities. Further studies are needed to reveal correlation between adrenomedullin, tyrosine hydroxylase and cold stress.
