Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması

ÜNÜBOL AYPAK, Serap; Tunca, Recai; ünübol, mustafa

Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması

Yürütücü

Serap ÜNÜBOL AYPAK (Adnan Menderes Üniversitesi, Veteriner Fakültesi, Biyokimya Anabilim Dalı, Aydın)

Araştırmacı(lar)

Mustafa ÜNÜBOL, (Adres Yazılmamış)

Recai TUNCA (Adres Yazılmamış)

39 14

Proje Grubu: SBAG Sayfa Sayısı: 95 Proje No: 117S796 Proje Bitiş Tarihi: 15.05.2019 Metin Dili: Türkçe İndeks Tarihi: 09-03-2020

Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması

Öz:

Bu çalışmada tatlandırıcıların metabolizma üzerine olan etkilerinin, obezite, tip 2 diyabet ve benzeri hastalıkları oluşturma potansiyelinin bazı metabolik parametrelerin araştırılması suretiyle belirlenmesi amaçlanmıştır. Bu amaçla, 40 adet dişi, 40 adet erkek Sprague Dawley rat kullanıldı. Gruplar; Grup I: Kontrol dişi grubu, (n=8). Grup II: Kontrol erkek grubu (n= 8). Grup III: % 0,4 aspartam dişi grubu (n=8). Grup IV: % 0,4 aspartam erkek grubu (n=8), Grup V: % 0,8 aspartam dişi grubu (n=8), Grup VI: % 0,8 aspartam erkek grubu (n=8), Grup VII: 4 mg/kg/gün Stevia dişi grubu (n=8), Grup VIII: 4 mg/kg/gün Stevia erkek grubu (n=8), Grup IX:8 mg/kg/gün: Stevia dişi grubu (n=8), Grup X: 8 mg/kg/gün Stevia erkek grubu (n=8 ) olacak şekilde düzenlendi. Ratlar standart ışık ve ısı da yeteri kadar su ve yem ile toplam 16 hafta süreyle beslendiler ve haftalık olarak kilo takipleri yapıldı. Tatlandırıcı kullanımının genel olarak kilo artışına sebep olduğu tespit edildi. Deneme sonunda otopsileri yapılan hayvanlardan kan ve doku örnekleri alınarak, serumda insülin, leptin, PYY, irisin, betatropin ve GLP-1 düzeyleri araştırıldı. Bu peptid ve hormon düzeylerinin erkeklerde dişilerden daha yüksek olduğu tespit edildi. Tatlandırıcıların analiz edilen peptid ve hormonlara etkisi değerlendirildiğinde, 4 mg/kg stevia verilen tüm ratların PYY, GLP-1 ve betatropin düzeylerinin kontrol gruplarından yüksek olduğu ve bu farkın istatistiksel olarak önemli olduğu tespit edildi.8 mg/kg stevianın karaciğer dokusunda mitoz ve apoptoz düzeylerini arttırdığı ve yaygın dejenerasyona sebep olduğu görüldü. Kabul edilebilir dozlarda stevia ve aspartamın da mitotik ve apoptotik değişikliklere neden olduğu tespit edildi. Bulgularımız, tatlandırıcıların, özellikle de stevianın kabul edilebilir limitlerinin tekrar gözden geçirilmesi gerektiğine işaret etmektedir. Bununla ilgili daha yapılmasıgerekmektedir.

Anahtar Kelime: stevia. PYY GLP-1 betatropin Aspartam

Konular: Endokrinoloji ve Metabolizma

Erişim Türü: Erişime Açık

Abdel-Salam, O.M., Salem, N.A., Hussein, J.S. 2012. “Effect of aspartame on oxidative stres and monoamine neurotransmitter levels in lipopolysaccharide-treated mice”, Neurotoxicity Research, 21, 245–255.
Abhilash, M., Paul, M.S., Varghese, M.V., Nair, H. 2011. “Effect of long term intake of aspartame on antioxidant defense status in liver”, Food and Chemical Toxicology, 49, 1203– 1207.
Abhilash, M., Sauganth Paul, M., Varghese, M.V., Nair, H. 2013. “Long-term consumption of aspartame and brain antioxidant defense status”, Drug and Chemical Toxicology, 36,135– 140.
Abou-Arab, E.A., Abu-Salem, F.M. 2010. “Evaluation of bioactive compounds of Stevia rebaudiana leaves and callus”, African Journal of Food and Science, 4, 627–634.
Alkafafy, M.E.S., İbrahim, Z.S., Ahmed, M.M., El-Shazly, S.A. 2015. “Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach”, International Journal ofImmunopathology and Pharmacology,28, 2, 247–255.
Alleva, R., Borghi, B., Santarelli, L., Strafella, E., Carbonari, D., Bracci, M., Marco Tomasetti, M. 2011. “In vitro effect of aspartame in angiogenesis induction”, Toxicology in Vitro, 25, 286–293.
Altuğ, T., Elmacı, Y. 2001. Sayfa 209-232. Tatlandırıcılar. In: Gıda Katkı maddeleri. Editör: Altuğ, T. İzmir: Bornova.
Amor, S., Puentes, F., Baker, D., Van Der Valk, P. 2010. “Inflammation in neurodegenerative diseases”, Immunology, 129, 54–169.
Arora, S., Anubhuti. 2006. “Role of neuropeptides in appetite regulation and obesity – a review”, Neuropeptides, 40, 375–401.
Ashok, I., Sheeladevi, R. 2014. “Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain”, Redox Biology, 2, 820– 831.
Ashok, I., Sheeladevi,R. 2015. “Neurobehavioral changes and activation of neurodegenerative apoptosis on long-term consumption of aspartame in the rat brain”, Journal of Nutrition & Intermediary Metabolism, 2, 76–85.
Ashok, I., Sheeladevi, R., Wankhar, D. 2013. “Long term effect of aspartame (artificial sweetener) on membrane homeostatic imbalance and histopathology in the rat brain”, Free Radicals and Antioxidants, 3, 42–49.
Ashok, I., Sheeladevi, R., Wankhar, D. 2014. “Effect of long-term aspartame (artificial sweetener) on anxiety, locomotor activity and emotionality behavior in Wistar albino rats”, Biomedicine and Preventive Nutrition, 4, 39–43.
Avena, N.M., Gold, M.S. 2011. “Food and addiction - sugars, fats and hedonic overeating”, Addiction, 106, 1214-1215.
Azeez, O., Alkass, S. 2018. “Effect of long-term consumption of aspartame on body weight, blood glucose, lipid profile, and kidney and liver fuction in rats”,International Journal of Current Advanced Research, 7, 7, 14464-14474.
Barceloux, D., Bond, G., Krenzelok, E., Cooper, H., Vale, J.A. 2002. “American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning”, Journal of Toxicology: Clinical Toxicology, 40, 415–446.
Barriocanal, L.A., Palacios, M., Benitez, G., Benitez, S., Jimenez, J.T., Jimenez, N., Rojas, V. 2008. “Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics”, Regulatory Toxicology Pharmacology, 51, 37-41.
Bell, L.N., Labuza, T.P. 1991. “Aspartame degradation kinetics as affected by pH in intermediate and low moisture food systems”, Journal of Food Science, 56,17–2.
Bender, C., Graziano, S., Zimmermann, B.F. 2015. “Study of Stevia rebaudiana Bertoni antioxidant activities and cellular properties”, International Journal of Food Science and Nutrition, 66, 5, 553–558.
Bergstrom, B.P., Cummings, D.R., Skaggs, T.A. 2007. “Aspartame decreases evoked extracellular dopamine levels in the rat brain: an in vivo voltammetry study”, Neuropharmacology, 53, 967–974.
Bernal, J., Mendiola, J., Ibanez, E., Cifuentes, A. 2011. “Advanced analysis of nutraceuticals”, Journal of Pharmaceutical and Biomedical Analysis, 55, 758–774.
Berthoud, H. R., Morrison, C. 2008. “The brain, appetite, and obesity”, Annual Review of Psychology, 59, 55–92.
Berthoud, H.R., Münzberg, H., Morrison, C. D. 2017. “Blaming the brain for obesity: integration of hedonic and homeostatic mechanisms”, Gastroenterology, 152, 1728–1738.
Blackburn, G.L., Kanders, B.S., Lavin, P.T., Keller, S.D., Whatley, J. 1997. “The effect of aspartame aspart of a multidisciplinary weight-control program on short- and long-term control of body weight”, The American Journal of Clinical Nutrition, 65, 409-18.
Blundell, J. 1991. “Pharmacological approaches to appetite suppression”, Trends in Pharmacological Sciences, 12, 147–157.
Blundell, J.E., Finlayson, G. 2011. “Food addiction not helpful: the hedonic component - implicit wanting - is important”, Addiction, 106, 1216-1218.
Boakes, R.A., Kendig, M.D., Martire, S.I., Rooney, K.B. 2016. “Sweetening yoghurt with glucose, but not with saccharin, promotes weight gain and increased fat pad mass in rats”, Appetite, 105, 114-128.
Boughton, C. K., Murphy, K. G. 2013. “Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity”, British Journal of Pharmacology, 170, 1333–1348.
Braz de Oliveira, A. J., Correia Goncalves, R. A., Cantuaria Chierrito, T. P., Muller dos Santos, M., Mera de Souza, L., Gorin, P. A. J.,Sassaki, L.G., Iacomini, M. 2011. “Structure and degree of polymerisation of fructooligosaccharides present in roots and leaves of Stevia rebaudiana (Bert.) Bertoni”, Food Chemistry, 129, 305–311.
Brown, R.J., Walter M., Rother, I. K. 2009. “Ingestion of Diet Soda Before a Glucose Load Augments Glucagon-Like Peptide-1 Secretion”,Diabetes Care, 32, 2184–2186.
Butchko, H.H., Kotsonis, F.N. 1991. “Acceptable daily intake vs actual intake: the aspartame example”, Journal of American College of Nutrition, 10, 258–266.
Butchko, H.H., Stargel, W.W., Comer, C.P., et al. 2002. “Aspartame: review of safety”, Regulatory Toxicology and Pharmacology, 35, 1-93.
Carakostas, M.C., Curry, L.L., Boileau, A.C., Brusick, D.J. 2008. “Overview: The history, technical function and safety of rebaudioside A, a naturally occurring steviol glycoside, for use in food and beverages”, Food Chemical Toxicology, 2008, 46, 1- 10.
Cecchini, M., Warin, L. 2016. “Impact of food labelling systems on food choices and eating behaviours: a systematic review and meta-analysis of randomized studies”, Obesity Reviews, 17, 201–210.
Cederbaum, A.I. 2012. “Alcohol metabolism”, Clinics in liver disease, 16, 667–685. Chambers, A. P., Sandoval, D. A., Seeley, R. J. 2013. “Integration of satiety signals by the central nervous system”, Current Biology, 23, 379–388.
Chan, P., Tomlinson, B., Chen, Y.J., Liu, J.C., Hsieh, M.H., Cheng, J.T. 2000. “A double blind placebo- controlled study of the effectiveness and tolerability of oral stevioside in human hypertension”, British Journal of Clinical Pharmacology, 50, 215-220.
Chatsudthipong, V., Muanprasat, C. 2009. “Stevioside and related compounds: Therapeutic benefits beyond sweetness”, Pharmacology & Therapeutics, 121, 41-54.
Choi, T.B., Pardridge, W.M. 1986. “Phenylalanine transport at the human blood-brain barrier. Studies with isolated human brain capillaries”, Journal of Biologycal Chemistry, 261, 6536– 6541.
Choudhary, A.K., Devi, R.S. 2014. “Serum biochemical responses under oxidative stress of aspartame in wistar albino rats”, Asian Pacific Journal of Tropical Disease, 4, 403–410.
Choudhary, A.K., Devi, R.S. 2015. “Longer period of oral administration of aspartame on cytokine response in Wistar albino rats”, Endocrinología y Nutrición, 62, 114–122.
Choudhary, A.K., Pretorius, E. 2017. “Revisiting the safety of aspartame”, Nutrition Reviews, 75(9), 718–730.
Choudhary, A.K., Rathinasamy, S.D. 2014. “Aspartame induces alteration in electrolytes homeostasis of immune organs in wistar albino rats”, Biomedicine & Preventive Nutrition, 4, 181–187.
Choudhary, A.K., Sundareswaran, L., Devi, R.S. 2016. “Effects of aspartame on the evaluation of electrophysiological responses in Wistar albino rats”, Journal of Taibah University for Science, 10, 505–51.
Christian, B., McConnaughey, K., Bethea, E.,Brantley, S., Coffey, A., Hammond, L., Harrell, S., Metcalf, K., Muehlenbein, D., Spruill, W., Brinson, L., McConnaughey, M. 2004. “Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na + , K + -ATPase in rats”, Pharmacology Biochemistry and Behavior, 78, 121–127.
Chunchai, T., Chattipakorn, N., Chattipakorn, S. C. 2018. “The possible factors affecting microglial activation in cases of obesity with cognitive dysfunction”, Metabolic Brain Disease, 33, 615–635.
Cieślińska-Swider J. 2015. “Physiotherapy in the comprehensive treatment of obesity”, Physiotherapy and Health Activity, 23, 34–43.
Cifre, M., Palou, A., Oliver, P. 2018. “Cognitive impairment in metabolically-obese, normal- weight rats: identification of early biomarkers in peripheral blood mononuclear cells”, Molecular Neurodegeneration, 13, 14.
Collipp, P.J., Chen, S.Y., Maitinsky, S. 1983. “Manganese in infant formulas and learning disability”, Annals of Nutrition and Metabolism, 27, 6, 488-94.
Contreras-Zentella, M.L., Hernandez-Munoz, R. 2016. “Is liver enzyme release really associated with cell necrosis induced by oxidant stress?”, Oxidative Medicine and Cellular Longevity, 3529149. doi:10.1155/2016/3529149
Curi, R., Alvarez, M., Bazotte, R.B. 1986. “Effect of Stevia rebaudiana on glucose tolerance in normal adult humans”, Brazilian Journal of Medical and Biological Research, 19, 6, 771– 774.
Curry, L.L., Roberts, A. 2008. “Subchronic toxicity of rebaudioside A”, Food and Chemical Toxicology, 46, 11–20.
D’Alessio, D. A., Prigeon, R. L., Ensinck, J.W. 1995. “Enteral enhancement of glucose disposition by both insulin-dependent and insulin-independent processes. A physiological role of glucagon-like peptide I”, Diabetes, 44, 1433–1437.
Dailey, J., Lasley, S., Burger, R., Bettendorf, A.F., Mishra, P.K., Jobe, P.C. 1991. “Amino acids, monoamines and audiogenic seizures in genetically epilepsy-prone rats: effects of aspartame”, Epilepsy Research, 8, 122–133.
Daubner, S.C., Melendez, J., Fitzpatrick, P.F. 2000. “Reversing the substrate specificities of phenylalanine and tyrosine hydroxylase: aspartate 425 of tyrosine hydroxylase is essential for L-DOPA formation”, Biochemistry, 39, 9652–9661.
Davidson, T.L., Martin, A.A., Clark, K., Swithers, S.E. 2011. “Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation”, The Quarterly Journal of Experimental Psychology (Hove), 64, 1430–41.
Davoli, E., Cappellini, L., Airoldi, L., Fanelli, R. 1986. “Serum methanol concentrations in rats and in men after a single dose of aspartame”, Food and Chemical Toxicology, 24, 187–189.
Denina, I., Semjonovs, P., Fomina, A., Treimane, R., Linde, R. 2014. “The influence of stevia glycosides on the growth of Lactobacillus reuteri strains”, Letters in Applied Microbiolgy, 58, 278–84.
Di Pasquale, M. 1998. “Use of nutritive and nonnutritive sweeteners”, Journal of American Dietetic Association, 98, 580–587.
Duggett, A. “Medications that contain aspartame” Drugsdb.com website. Güncellenme tarihi: 2012. http:// www.drugsdb.com/cib/aspartame/medications-that-contain-aspartame/ Erişim tarihi: 11.03.2019.
Duncan, D.B. 1955. “Multiple Range and Multiple F Tests”, Biometrics, 11, 1-42.
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). 2010. “Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive”, EFSA Journal, 8(4), 1537.
Elnaga, N.I.E. A., Massoud, M.I., Yousef, M.I, Mohamed, H.H.A. 2016. “Effect of stevia sweetener consumption as non-caloric sweetening on body weight gain and biochemical’s parameters in overweight female rats”, Annals of Agricultural Science, 61, 1, 155–163.
El-Samad, A.A. 2010. “Light and electron microscopic study on the effect of aspartame on the cerebellar cortex of male albino rat”, The Egyptian Journal of Histology, 33, 419–430.
Euston, D.R., Gruber, A.J., McNaughton, B.L. 2012. “The role of medial prefrontal cortex in memory and decision making” , Neuron, 76, 1057–1070.
Feijó, F.M.,Ballard C.R.,Foletto, K.C., Batista, B.A.M., Neves, A.M., Ribeiro, M.F.M.,Bertoluci, M.C. 2013. “Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels”, Appetite, 60, 203-207.
FM Biro, M.W. 2010. “Childhood obesity and adult morbidites”, American Journal of Clinical Nutrition, 91,1499–1505.
Foletto, K.C., Batista, B.A.M., Neves, A.M., Feijó, F.M.,Ballard, C.R., Ribeiro, M.F.M., Bertoluci, M.C. 2016. “Sweet taste of saccharin induces weight gain without increasingcaloric intake, not related to insulin-resistance in Wistar rats”, Appetite, 96, 604-610.
Fowler, S.P. 2016. “Low-calorie sweetener use and energy balance: results from experimental studies in animals, and large-scale prospective studies in humans”, Physiology & behavior, 164, 517–523.
Fowler, S.P., Williams, K., Resendez, R.G., Hunt, K.J., Hazuda, H.P., Stern, M.P. 2008. “Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain”, Obesity (Silver Spring), 16 (8), 1894–1900.
Gardana, C., Scaglianti, M., Simonetti, P. 2010. “Evaluation of steviol and its glycosides in Stevia rebaudiana leaves and commercial sweetener by ultra-high-performance liquid chromatography-mass spectrometry”, Journal of Chromatography A, 1217, 9, 1463–1470.
Gardana, C., Simonetti, P., Canzi, E., Zanchi, R., Pietta, P. 2003. “Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora”, Journal of Agricultural Food and Chemistry, 51, 6618–22.
Geliebter, A. 1988. “Gastric and capacity in relation to food intake in humans”, Physiology & Behavior, 44, 665–668.
Gerlach, M., Ben-Shachar, D., Riederer, P., Youdim, M.B. 1994. “Altered brain metabolism of iron as a cause of neurodegenerative diseases?”, Journal of Neurochemistry, 63, 3, 793-807. Geuns, J.M., Buyse, J., Vankeirsbilck, A., Temme, E.H. 2007. “Metabolism of stevioside by healthy subjects”, Experimental Biology and Medicine, 232, 164-73.
Ghanta, S. Banerjee, A., Poddar A., Chattopadhyay S. 2007. “Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (Bertoni) Bertoni, a natural sweetener”, Journal of Agricultural and Food Chemistry, 55, 10962-10967.
Goerss, A.L., Wagner, G.C., Hill, W.L. 2000. “Acute effects of aspartame on aggression and neurochemistry of rats”, Life Sciences, 67, 1325–1329.
Goldstone, A. P., Prechtl de Hernandez, C., Beaver, J. D., Muhammed, K., Croese, C., Bell, G., Durighel, G., Hughes, E., Waldman, A. D., Bell, J. D. 2009. “Fasting biases brain reward systems towards high-calorie foods”, European Journal of Neuroscience, 30, 1625–1635.
Goldstone, A. P., Prechtl, C. G., Scholtz, S., Miras, A. D., Chhina, N., Durighel, G., Deliran, S. S., Beckmann, C., Ghatei, M. A., Ashby,D. R., Waldman, A. D., Gaylinn, B. D., Thorner,M. O., Frost, G. S., Bloom, S. R., Bell, J. D. 2014. “Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food”, The American Journal of Clinical Nutrition, 99, 1319–1330.
Gombos, K., Varjas, T., Orsόs, Z., Polyak, E., Peredi, J., Varga, Z., Nowrasteh, G., Tettinger, A., Mucsi, G., Ember, I. 2007. “The effect of aspartame administration on oncogene and suppressor gene expressions”, In Vivo, 21, 89–92.
Goyal, S. K., Samsher, Goyal, R. K. 2010. “Stevia (Stevia rebaudiana) a bio-sweetener: areview”, International Journal of Food Sciences and Nutrition, 61, 1, 1-10.
Gregersen, S., Jeppesen, P. B., Holst, J. J., Hermansen, K. 2004. “Antihyperglycemic Effects of Stevioside in Type 2 Diabetic Subjects”, Metabolism, 53, 1, 73-76.
Gu, Y., Dee, C., Shen, J. 2010. “Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability”, Frontiers in Bioscience, 3, 1216–1231.
Gu, Y., Zheng, G., Xu, M.,Chen, X., Zhu, W., Tong, Y., Chung, S.K., Liu, K.J., Shen, J. 2012. “Caveolin-1 regulates nitric oxide-mediated matrixmetalloproteinases activity and blood–brain barrier permeability in focal cerebral ischemia and reperfusion injury”, Journal of Neurochemistry, 120, 147–156.
Gudadhe, D.R., Talhar, S.S., Bokariya, P., Shende, M.R., Tarnekar, A.M. 2013. “Histo- morphometric demonstration of cardiotoxic effects of aspartame on mice”, IOSR Journal Of Pharmacy, 3, 30–33.
Hansen, J.M., Contreras, K.M., Harris, C. 2005. “Methanol, formaldehyde, and sodium formate exposure in rat and mouse conceptuses: a potential role of the visceral yolk sac in embryotoxicity”, Birth Defects Research (Part A), 73, 72–82.
Haorah, J., Ramirez, S.H., Schall, K., Smith D., Pandya R. Persidsky, Y. 2007. “Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood–brain barrier dysfunction”, Journal of Neurochemistry, 101, 566–576.
Harrold, J. A., Dovey, T.M., Blundell, J. E., Halford, J. C. 2012. “CNS regulation of appetite”, Neuropharmacology, 63, 3–17.
Özdamar, K. 1999. Sayfa 353-355. SPSS ile Biyoistatistik (3. Basım) Eskişehir: Kaan Kitap.
Higgins, K.A., Considine, R.V., Mattes, R.D. 2018. “Aspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body Weight of Healthy, Lean Adults in a Randomized Controlled Trial”, The Journal of Nutrition Ingestive Behavior and Neurosciences, 148, 650–657.
Horwitz, D.L., McLane, M., Kobe, P. 1988. “Response to single dose of aspartame or saccharin by NIDDM patients”, Diabetes Care, 11, 230-4.
Hsieh, H.M.,Chan ,P., Sue, Y.M., Liu, J.C., Liang, T.H., Huang, T.Y., Tomlinson, B., Pharm, M.S.S.C., Kao, P.F., Chen, Y.J. 2003. “Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: A two-year, randomized, placebo-controlled study”, Clinical Therapeutics, 25,11, 2797-2808.
Humphries, P., Pretorius, E., Naude, H. 2008. “Direct and indirect cellular effects of aspartame on the brain”, European journal of Clinical Nutrition, 62, 451–462.
Hussain, S., Bloom, S. 2013. “The regulation of food intake by the gut-brain axis: 431 implications for obesity”, International Journal of Obesity, 37, 625–633.
Iman, M.M. 2011. “Effect of aspartame on some oxidative stress parameters in liver and kidney of rats”, African Journal of Pharmacy and Pharmacology, 5, 678–682.
Iyyaswamy, A., Rathinasamy, S. 2012. “Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats”, Journal of Biosciences, 37, 679–688.
Jeppesen, P.B., Gregersen, S., Alstrup, K.K., Hermansen, K. 2002. “Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: Studies in the diabetic Goto-Kakizaki (GK) rats”, Phytomedicine, 9, 9-14.
Johlin, F.C., Fortman, C.S., Nghiem, D., Tephly, T.R. 1987. “Studies on the role of folic acid and folate-dependent enzymes in human methanol poisoning”, Molecular Pharmacology, 31, 557–561.
Karagöz, Ş., Demirdöven, A. 2018. “Stevia rebaudiana Bitkisinin Tatlandırıcı, Antioksidan ve Antimikrobiyal Özellikleri”, Akademik Gıda, 16, 4, 431-438.
Karaköse, H., Müller, A., Kuhnert, N. 2015. “Profiling and quantification of phenolics in Stevia rebaudiana leaves”, Journal of Agricultural and Food Chemistry, 63, 9188–9198.
Karatay, C.E. 2011. Sayfa 201-225. Şeker, neden tatlı tatlı zehirler. In: Kansere çözüm var. İstanbul.
Kawaratani, H., Tsujimoto, T., Douhara, A., Takaya, H., Moriya, K., Namisaki, T., Noguchi, Hitoshi Yoshiji, R., Fujimoto, M., Fukui, H. 2013. “The effect of inflammatory cytokines in alcoholic liver disease”, Mediators of Inflammation, 495156. doi:10.1155/ 2013/495156
Kelmer Bracht, A., Alvarez, M., Bracht, A. 1985. “Effects of Stevia rebaudiana natural products on rat liver mitochondria”, Biochemical Pharmacology, 34, 6, 873–882.
Khiraoui, A., Bakha, M., Amchra, F., Ourouadi, S., Boulli, A., Al-Faiz, C., Hasib, A. 2017. “Nutritional and biochemical properties of natural sweeteners of six cultivars of Stevia rebaudiana Bertoni leaves grown in Morocco”, Journal of Materials and Environmental Sciences, 8, 3, 1015-1022.
Kim, J., Seok, Y.M., Jung, K-J., Park, K.M. 2009. “Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice”, American Journal of Physiology Renal Physiology, 297, 461–470.
Kim, J.Y., Seo, J., Cho, K.H. 2011. “Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia”, Food and Chemical Toxicology, 49, 2899–2905.
Knight, J.A. 2000. “Review: free radicals, antioxidants, and the immune system”, Annals of Clinical & Laboratory Science, 30,145–158.
Koeppen, B.M. 2009. “The kidney and acid-base regulation”, Advences in Physiology Education, 33, 275–281.
Koyuncu Ünsal, B. 2013. Sayfa 79. Prediabetiklerde Aspartam ve Diyet Değişikliklerinin Kan Şekeri Üzerine Etkisi. Yan Dal Uzmanlık Tezi, Akdeniz Üniversitesi Tıp Fakültesi İç Hastalıkları Anabilim Dalı, Antalya.
Kubrak, O.I., Husak, VV., Rovenko, B.M., Storey, J.M., Storey, K.B., Lushchak, V.I. 2011. “Cobalt-induced oxidative stress in brain, liver and kidney of goldfish Carassius auratus”, Chemosphere, 85, 6, 983-9.
Kumar Choudhary, A., Selvaraj, S., Sheela Devi, R. 2014. “Aspartame induce modification in membrane bound and antioxidant enzymes in liver and kidney of Wistar albino rats”, Current Nutrition & Food Science, 10, 275–287.
Kunová, G., Rada, V., Vidaillac, A., Lisova, I. 2014. “Utilisation of steviol glycosides from Stevia rebaudiana (Bertoni) by lactobacilli and bifidobacteria in in vitro conditions”, Folia Microbiologica (Praha), 59, 251–5.
Kushner, R. F. 2014. “Weight loss strategies for treatment of obesity”, Progress in Cardiovascular Diseases, 56, 465–472.
Larhammar, D. 1996. “Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide”, Regulatory Peptides, 65, 165–174.
Larsson, L. I., Sundler, F., Håkanson, R. 1975. “Immunohistochemical localization of human pancreatic polypeptide (HPP) to a population of islet cells”, Cell and Tissue Research, 156, 167–171.
Mace, O.J., Affleck, J., Patel, N., Kellett, G.L. 2007. “Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2”, The Journal of Physiology, 582(Pt 1), 379–392.
Macedo, I.C., Medeiros, L.F., Oliveira, C., Oliveira, C.M., Rozisky, J.R., Scarabelot, V.L., Souza, A., Silva, F.R., Santos, V.S., Cioato, S.G., Caumo, W., Torres, I.L.S. 2012. “Cafeteria diet-induced obesity plus chronic stress alter serum leptin levels”, Peptides, 38, 1, 189-96.
Magnuson, B., Burdock, G., Doull J., Kroes, R.M., Marsh, G.M., Pariza, M.W., Spencer, P.S., Waddell, W.J., Walker, R., Williams, G. M. 2007. “Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies”, Critical Reviews in Toxicology, 37, 629–727.
Maki, K.C., Curry, L.L., Carakostas, M.C., Tarka, S.M., Reeves, M.S., Farmer, M.V., McKenney, J.M., Toth, P.D., Schwartz, S.L., Lubin, B.C., Dicklin, M.R., Boileau, A.C., Bisognano, J.D. 2008. “The hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure”, Food and Chemical Toxicology, 46 (Suppl. 7), 40-46.
Manchanda, S., Kaur, G. 2017. “Withania somnifera leaf alleviates cognitive dysfunction by enhancing hippocampal plasticity in high fat diet induced obesity model”, BMC Complementary and Alternative Medicine, 17, 136.
Marchesi, J.R., Adams, D.H., Fava, F., Hermes, G.D.A., Hirschfield, G.M., Hold, G., Quraishi, M.N., Kinross, J., Smidt, H., Tuohy, K.M., Thomas, L.V., Zoetendal, E.G., Hart, A. 2016. “The gut microbiota and host health: a new clinical frontier”, Gut, 65, 330–9.
Mariani, E., Polidori, M., Cherubini, A., Mecocci, P. 2005. “Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview” Journal of Chromatography B, 827, 65–75.
Martins, M.R.I., Azoubel, R. 2007. “Effects of aspartame on fetal kidney: a morphometric and stereological study”, International Journal of Morphology, 25, 689–694.
McArdle, W.D., Katch, F.I., Katch, V.L. 2010. Page 3-17. Section I. Essentials of exercise physiology. Philadelphia: Lippincott Williams and Wilkins.
McBain, C., Mayer, M. 1994. “N-methyl- D-aspartic acid receptor structure and function”, Physiological Reviews, 74, 723–760.
Mediesse-Kengne, F., Woguia, A.L., Fogue, P., Atogho-Tiedeu, B., Simo, G., Boudjeko, T. 2014. “Antioxidant properties of cell wall polysaccharides of Stevia rebaudiana leaves”, Journal of Coastal Life Medicine, 2, 12, 962–9.
Melis, M.S. 1992. “Stevioside effect on renal function of normal and hypertensive rats”, Journal of Ethnopharmacology, 36, 213–217.
Melis, M.S. 1996. “A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats”. Brazilian Journal of Medical and Biological Research, 29, 669–675.
Mishra, N. 2011. “An Analysis of antidiabetic activity of Stevia rebaudiana extract on diabetic patient”, Journal of Natural Sciences Research, 1, 3, 1-9.
Montalvo-Jave, E.E., Escalante-Tattersfield, T., Ortega-Salgado, J.A., Pina, E., Geller, D.A. 2008. “Factors in the pathophysiology of the liver ischemia-reperfusion injury”, Journal of Surgical Research, 147, 153–159.
Morris, J. S., Dolan, R. J. 2001. “Involvement of human amygdala and orbitofrontal cortex in hunger-enhanced memory for food stimuli”, Journal of Neuroscience, 21, 5304-5310.
Muriel, P., Gordillo, K.R. 2016. “Role of oxidative stress in liver health and disease”, Oxidative Medicine and Cellular Longevity, 2016:9037051. doi:10.1155/2016/9037051
Nakanishi, K., Kamikubo, T., Matsuno, R. 1985. “Continuous synthesis of N- (benzyloxycarbonyl)- L aspartyl-L-phenylalanine methyl ester with immobilized thermolysin in an organic solvent”, Natura Biotechnology, 3, 459–464.
Narayanaswami, V., Dwoskin, L. P. 2017. “Obesity: Current and Potential Pharmacotherapeutics and Targets”, Pharmacology & Therapeutics, 170, 116–147.
National PKU News website. Drug products containing phenylalanine. https://pkunews.org/drug-products-containing-phenylalanine/. Güncelleme tarihi: 2007. Erişim tarihi: 11.03.2019.
Noitem, R., Yuajit, C., Soodvilai, S., Muanprasat, C., Chatsudthipong, V. 2018. “Steviol slows renal cyst growth by reducing AQP2 expression and promoting AQP2 degradation”, Biomedicine & Pharmacotherapy, 101, 754–762.
Nordentoft, I., Jeppesen, P.B., Hong, J., Abudula, R., Hermansen, K. 2008. “Isosteviol increases insulin sensitivity and changes gene expression of key insülin regulatory genes and transcription factors in islets of the diabetic KKAy Mouse”, Diabetes Obesity and Metabolism, 10, 939−949.
Olanow, C.W., Obeso, J.A., Stocchi, F. 2006. “Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications”, The Lancet Neurology, 5, 8, 677-87.
Oppermann, J.A. 1984. Aspartame metabolism in animals. In: Stegink LD, Filer Jr LJ, eds. Aspartame: Physiology and Biochemistry. New York, NY: Marcel Dekker. 141–159.
Paixao, J.A., Rodrigues, J.B., Esmerino, E.A., Cruz A.G., Bolini H.M.A. 2014. “Influence of temperature and fat content on ideal sucrose concentration, sweetening power, and sweetness equivalence of different sweeteners in chocolate milk beverage”, Journal of Dairy Science, 97, 7344–7353.
Palmnas, M.S., Cowan, T.E., Bomhof, M.R., Su, J., Reimer, R.A., Vogel, H.J., Hittel, D.S., Shearer, J. 2014. “Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat”, PLoS One, 9(10), e109841.
Park, C.H., Choi, S.H., Piao, Y., Kim, S.H., Lee,Y.J., Kim, H.S., Jeong, S.J., Rah, J.C., Seo, H.J., Lee, J.H., Chang, K.A., Jung, Y.J., Suh, Y.H. 2000. “Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice”, Toxicology Letters, 115, 117–125.
Pepino, M. Y. 2015. “Metabolic effects of non-nutritive sweeteners”, Physiology & Behavior, 152, 450-455.
Pepino, M.Y., Bourne, C. 2011. “Non-nutritive sweeteners, energy balance, and glucose homeostasis”, Current Opinion in Clinical Nutrition and Metabolic Care, 14, 391–395.
Piloni, N.E., Fermandez, V., Videla, L.A., Puntarulo, S. 2013. “Acute iron overload and oxidative stress in brain”, Toxicology, 314,1, 174-82.
Piñero, D.J., Connor, J.R. 2000. “Iron in the brain: an important contributor in normal and diseased states”, Neuroscientist, 6, 6, 435-53.
Prashant, G., Patil, R.B., Nagaraj, T., Patel, V.B. 2012. “The antimicrobial activity of the three commercially available intense sweeteners against common periodontal pathogens: an in vitro study”, The Journal of Contemporary Dental Practice, 13, 749–752.
Preiss, K., Brennan, L., Clarke, D. 2013. “A systematic review of variables associated with the relationship between obesity and depression”, Obesity Reviews, 14, 906–918.
Quinlan, M., Mialon, V., Everitt, M. 1999. Page 58-63. Effect of storage on the flavours of cola drinks sweetened with different sweetener systems. In: Corti, ed: Low-Calorie Sweeteners: Present and Future. Basel, Switzerland: Karger Publishers.
Rencüzoğulları, E., Tüylü, B.A., Topaktaş, M., İla, HB., Kayraldız, A., Arslan, M., Diler, S.B. 2004. “Genotoxicity of Aspartame”, Journal Drug and Chemical Toxicology, 27, 3, 257-268.
Renwick, A., Nordmann, H. 2007. “First European conference on aspartame: putting safety and benefits into perspective Synopsis of presentations and conclusions”, Food and Chemical Toxicology, 45, 1308–1313.
Roberts, A., Renwick, A.G. 2008. “Comparative toxicokinetics and metabolism of rebaudioside A, stevioside, and steviol in rats”, Food and Chemical Toxicology, 46, 31-9.
Samuel, P., Ayoob, K.T., Magnuson, B.A., Wölwer-Rieck, U., Jeppesen, P.B., Rogers, P.J., Rowland, I., Mathews, R. 2018.“Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential”, The Journal of Nutrition, 148, 1186–1205.
Savita, S.M., Sheela, K., Sunanda, S., Shankar, A.G., Ramakrishna, P. 2004. “Stevia rebaudiana A: functional component for food industry”, Journal of Human Ecology, 15, 261– 264.
Schwartz, M.W., Baskin, D. G., Bukowski, T. R., Kuijper, J. L., Foster, D., Lasser, G., Prunkard, D. E., Porte, D., Jr.,Woods, S. C., Seeley, R. J., Weigle, D. S. 1996. “Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice”, Diabetes, 45, 531–535.
Schwartz, M.W., Figlewicz, D. P., Baskin, D. G., Woods, S. C., Porte, D. 1992. “Insulin in the brain: a hormonal regulator of energy balance”, Endocrine Reviews, 13, 387-414.
Sehar, I., Kaul, A., Bani, S., Pal, H.C., Saxena, A.K. 2008. “Immune up regulatory response of a non-caloric natural sweetener, stevioside”, Chemico-Biological Interaction, 173, 115–121.
Selzner, N., Rudiger, H., Graf, R., Clavien, P.A. 2003. “Protective strategies against ischemic injury of the liver”, Gastroenterology, 125, 917–936.
Shen, M.J., Zipes, D.P. 2014. “Role of the autonomic nervous system in modulating cardiac arrhythmias”, Circulation Research, 114,1004–1021.
Shivanna, N., Naika, M., Khanum, F., Kaul, V.K. 2013. “Antioxidant, antidiabetic and renal protective properties of Stevia rebaudiana”, Journal of Diabetes and its Complication, 27, 103–113.
Shukla, S., Mehta, A., Bajpai, V.K., Shukla, S. 2009. “In vitro antioxidant activity and total phenolic content of ethanolic leaf extract of Stevia rebaudiana Bert”, Food Chemical Toxicology, 47, 2338-43.
Simintzi, I., Schulpis, K.H., Angelogianni, P., Liapi, C., Tsakiris, S. (a). 2007. “The effect of aspartame on acetylcholinesterase activity in hippocampal homogenates of suckling rats”, Pharmacological Research, 56, 155–159.
Simintzi, I., Schulpis, K.H., Angelogianni, P., Liapi, C., Tsakiris, S. (b) 2007. “The effect of aspartame metabolites on the suckling rat frontal cortex acetylcholinesterase. An in vitro study”, Food and Chemical Toxicology, 45, 2397–2401.
Soffritti, M., Belpoggi, F., Tibaldi, E., Esposti, D.D., Lauriola, M. 2007. “Life span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats”, Environmental Health Perspectives, 115, 1293–1297.
Soffritti, M., Padovani, M., Tibaldi, E. Falcioni, L., Manservisi, F. Belpoggi, F.2014. “The carcinogenic effects of aspartame:the urgent need for regulatory re-evaluation”, American Journal of Industrial Medicine, 57, 383–397.
Sonnen, J.A., Larson, E.B., Gray, S.L., Wilson, A., Kohama, S.G., Crane, P.K., Breitner, J.C.S., Montine, T.J. 2009. “Free radical damage to cerebral cortex in Alzheimer’s disease, microvascular brain injury, and smoking”, Annals of Neurology, 65, 226–229.
Södersten, P., Bergh, C., Leon, M., Brodin, U., Zandian, M. 2017. “Cognitive behavior therapy for eating disorders versus normalization of eating behavior”, Physiology &. Behavior, 174, 178–190.
Spanel, P., Dryahina, K., Vicherkova, P., Smith, D. 2015. “Increase of methanol in exhaled breath quantified by SIFT-MS following aspartame ingestion”, Journal of Breath Research, 9(4), 047104.
Stanley, S., Wynne, K., McGowan, B., Bloom, S. 2005. “Hormonal Regulation of Food Intake”, Physiological Reviews, 85, 1131–1158.
Steele, C. A., Cuthbertson, D. J., MacFarlane, I. A., Javadpour, M., Das, K. S., Gilkes, C., Wilding, J. P., Daousi, C. 2013. “Hypothalamic obesity: prevalence, associations and longitudinal trends in weight in a specialist adult neuroendocrine clinic”, European Journal of Endocrinology, 168, 501–507.
Stegink, L.D., Filer, L., Bell, E.F., Ziegler, K.E., Tephly, T.R., Krause, W.L. 1990. “Repeated ingestion of aspartame-sweetened beverages: further observations heterozygous for phenylketonuria”, Metabolism, 39, 1076–1081.
Stice, E., Burger, K., Yokum, S. 2013. “Caloric deprivation increases responsivity of attention and reward brain regions to intake, anticipated intake, and images of palatable foods”, Neuroimage, 67, 322–330.
Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C.A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Kuperman, Y., Harmelin, A., Kolodkin-Gal, I., Shapiro, H., Halpern, Z., Segal, E., Elinav, E. 2014. “Artificial sweeteners induce glucose intolerance by altering the gut microbiota”, Nature, 514, 181–186.
Sun, J.P., Han, Q., Zhang, X.Q., Ding M.Y. 2014. “Investigation on the degradation of aspartame using high-performance liquid chromatography/tandem mass spectrometry”, Chinese Chemical Letters, 25, 1259–1264.
Sureshbabu, A., Ryter, S.W., Choi, M.E. 2015. “Oxidative stress and autophagy: crucial modulators of kidney injury”, Redox Biology, 4, 208–214.
Swithers, S.E., Laboy, A.F., Clark K., Cooper, S., Davidson, T.L. 2012. “Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats”, Behavioural Brain Research, 233, 1–14.
Sylvetsky, A., Rother, K.I., Brown, R. 2011. “Artificial sweetener use among children: epidemiol,recommendations, metabolic outcomes, and future directions”, Pediatric clinics of North America, 58, 6, 1467–1480.
Tadhani, M.B., Patel, V.H., Subhash, R. 2007. “In vitro antioxidant activities of Stevia rebaudiana leaves and callus”, Journal of Food Composition and Analysis, 20, 323–329.
Tolle, V., Kadem, M., Bluet-Pajot, M.T., Frere, D., Foulon, C., Bossu, C., Dardennes, R., Mounier, C., Zizzari, P., Lang, F., Epelbaum, J., Estour, B. 2003. ”Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women”, The Journal of Clinical Endocrinology and Metabolism, 88, 109–116.
Trebotic, L.K., Klimek, P., Thomas, A., Fenzl, A., Leitner, K., Springer, S, Kiefer, F.W., Kautzky-Willer, A. 2015. “Circulating Betatrophin Is Strongly Increased in Pregnancy and Gestational Diabetes Mellitus”, PLoS ONE, 10, 9, e0136701. https://doi.org/10.1371/journal.pone.013670
Turton, M. D., O’Shea, D., Gunn, I., Beak, S. A., Edwards, C. M., Meeran, K., Choi, S. J., Taylor, G.M., Heath, M.M., Lambert, P. D.,Wilding, J. P., Smith, D.M., Ghatei, M. A., Herbert, J., Bloom, S. R. 1996. “A role for glucagon-like peptide-1 in the central regulation of feeding”, Nature, 379, 69–72.
Türk Gıda Kodeksi. 2002. Sayfa 2-7. Gıdalarda Kullanılan Tatlandırıcılar Tebliğinde Değişiklik Yapılması Hakkında Tebliğ. Resmi Gazete, 11.10.2002 – 24903.
US Food and Drug Administration. 2006. “Artificial sweetwners: no calories...sweet!” FDA Consumer Magazine, 40, 4, 27-28.
USDA Nutrient Data Laboratory, Food and Nutrition Information Center, and Information Systems Division of the National Agricultural Library. USDA Food Compostion Databases. https://ndb.nal.usda.gov/ndb/. Erişim Tarihi: 11.03.2019.
Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T.D., Mazur, M., Telser, J. 2007. “Free radicals and antioxidants in normal physiological functions and human disease”, The International Journal of Biochemistry and Cell Biology, 39, 44–84.
Vaško, L.,Vašková, J., Fejerčáková, A., Mojžišová, G., Poráčová, J. 2014. “Comparison of some antioxidant properties of plant extracts from Origanum vulgare, Salvia officinalis. Eleutherococcus senticosus and Stevia rebaudiana”, In Vitro Cellular & Development Biology Animal, 50, 614–622.
Vences-Mejı, A., Labra-Ruı ́z, N., Herna ́ndez-Martı ́nez, N., Dorado-Gonza ́lez, V., Go ́mez- Gardun ̃o, J., Pe ́rez-Lo ́pez, I., Nosti-Palacios, R., Camacho Carranza, R., Espinosa-Aguirre, J.J. 2006. “The effect of aspartame on rat brain xenobiotic-metabolizing enzymes”, Human & Experimental Toxicology, 25, 453–459.
Vianna, H.R., Soares, C.M.B.M., Tavares, M.S., TeixeiraM.M., Silva, A.C.S. 2011. “Inflammation in chronic kidney disease: the role of cytokines”, Brazilian Journal of Nephrology, 33, 351–364.
Victor, V.M., De La Fuente, M. 2003. “Immune cells redox state from mice with endotoxin induced oxidative stres Involvement of NF-kB”, Free Radical Research, 37, 19–27.
Villareal, L.M.A., Cruz, R.A.M., Ples, M.B., Vitor, R.J.S. 2016. “Neurotropic effects of aspartame, stevia and sucralose on memory retention and on the histology of the hippocampus of the ICR mice (Mus musculus)”, Asian Pacific Journal of Tropical Biomedicine, 6, 114–118.
von Borell, E., Langbein, J., Despre ́s, G.,Hansen S., Leterrier, C., Marchant-Forde, J., Marchant-Forde, R., Minero, M.,Mohr, E., Prunier, A., Valance, D., Veissier I. 2007. “Heart rate variability as a measure of autonomic regulation of cardiac activity for assessing stress and welfare in farm animals—a review”, Physiology Behavior, 92, 293–316.
Weglage, J., Wiedermann, D., Denecke, J.,Feldmann, R., Koch, H.G., Ullrich, K., Harms, E., Möller, H.E. 2001. “Individual blood–brain barrier phenylalanine transport determines clinical outcome in phenylketonuria”, Annals of Neurology, 50, 463–467.
Weihrauch, M.R., Diehl, V. 2004. “Artificial sweeteners do they bear a carcinogenic risk?”, Annals of Oncology, 15, 1460-1465.
Welsh, P., Lowe, G.D., Chalmers, J., Campbell, D.J., Rumley, A., Neal, B.C., MacMahon, S.W., Woodward, M. 2008. “Associations of proinflammatory cytokines with the risk of recurrent stroke”, Stroke, 39, 2226–2230.
Wetzel, C.R., Bell, L.N. 1998. “Chemical stability of encapsulated aspartame in cakes without added sugar”, Food Chemistry, 63, 33–37.
Wheeler, A., Boileau, A.C., Winkler, P.C., Compton, J.C., Prakash, I., Jiang, X., Mandarino, D.A. 2008. “Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men”, Food and Chemical Toxicology, 46, 54−60.
Wheeler, M.D. 2003. “Endotoxin and Kupffer cell activation in alcoholic liver disease”, Alcohol research and Health, 27, 300–306.
WHO 2016. WHO Report 2016. http://www.who.int/mediacentre/factsheets/fs311/en/ Erişim tarihi: 02.05.2018.
Xiong, X.Q., Chen, D., Sun, H.J., Ding, L., Wang, J.J., Chen, Q., Li, Y.H., Zhou, Y.B., Han, Y., Zhang, F., Gao, X.Y., Kang, Y.M., Zhu, G.Q. 2015. “FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity”, Biochimica BiophysicaActa, 1852, 9,1867-75.
Yasukawa, K., Kitanaka, S., Seo, S. 2002. “Inhibitory effect of stevioside on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis”, Biological and Pharmceutical Bulletin, 25, 1488−1490.
Yılmaz, S., Uçar, A. 2014. “A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?”, Cytotechnology, 66, 875–881.
Yuajit, C., Chatsudthipong, V. 2016. “Nutraceutical for Autosomal Dominant Polycystic Kidney Disease Therapy”, Journal of Medical Association of Thailand, 99, 1, 97–103.
Yuajit, C., Muanprasat, C., Gallagher, A.R., Fedeles, S.V. Kittayaruksakul, S., Homvisasevongsa, S., Somlo, S., Chatsudthipong, V. 2014. “Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a Mouse model of polycystic kidney disease”, Biochemical Pharmacology, 88, 412–421.
Yurttagül, M., Ayaz, A. 2008. Sayfa 12-13. Katkı maddeleri; Yanlışlar ve Doğrular. Sağlık Bakanlığı Yayınları. ISBN: 978-975-590-243-2. Ankara.
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., Friedman, J. M. 1994. “Positional cloning of the mouse obese gene and its human homologue”, Nature, 372, 425– 432.

APA	ÜNÜBOL AYPAK S, ünübol m, Tunca R (2019). Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. , 1 - 95.
Chicago	ÜNÜBOL AYPAK Serap,ünübol mustafa,Tunca Recai Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. (2019): 1 - 95.
MLA	ÜNÜBOL AYPAK Serap,ünübol mustafa,Tunca Recai Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. , 2019, ss.1 - 95.
AMA	ÜNÜBOL AYPAK S,ünübol m,Tunca R Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. . 2019; 1 - 95.
Vancouver	ÜNÜBOL AYPAK S,ünübol m,Tunca R Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. . 2019; 1 - 95.
IEEE	ÜNÜBOL AYPAK S,ünübol m,Tunca R "Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması." , ss.1 - 95, 2019.
ISNAD	ÜNÜBOL AYPAK, Serap vd. "Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması". (2019), 1-95.

APA	ÜNÜBOL AYPAK S, ünübol m, Tunca R (2019). Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. , 1 - 95.
Chicago	ÜNÜBOL AYPAK Serap,ünübol mustafa,Tunca Recai Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. (2019): 1 - 95.
MLA	ÜNÜBOL AYPAK Serap,ünübol mustafa,Tunca Recai Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. , 2019, ss.1 - 95.
AMA	ÜNÜBOL AYPAK S,ünübol m,Tunca R Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. . 2019; 1 - 95.
Vancouver	ÜNÜBOL AYPAK S,ünübol m,Tunca R Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması. . 2019; 1 - 95.
IEEE	ÜNÜBOL AYPAK S,ünübol m,Tunca R "Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması." , ss.1 - 95, 2019.
ISNAD	ÜNÜBOL AYPAK, Serap vd. "Diyetlerine Tatlandırıcı İlave Edilen Ratlarda Bazı Peptid ve Hormon Düzeylerinin Araştırılması". (2019), 1-95.