Tip 2 Diyabetli Ratlarda Doğal ve Yapay Tatlandırıcıların Glukoz İntoleransı, Karaciğer Enzimleri ve Oksidatif Stres Üzerine Etkisi

Yıl 2024, Cilt: 13 Sayı: 4, 1518 - 1526, 25.12.2024

Merve Pehlivan , Eda Köksal

Öz

Bu çalışmanın amacı, doğal ve yapay tatlandırıcıların glukoz intoleransı, karaciğer enzimleri ve oksidatif stres üzerine etkisini araştırmaktır.
Altmış adet erişkin erkek Wistar rat, rastgele her grupta 30 adet olacak şekilde 2 gruba ayrılmştır. İlk grup streptozosin ile diyabetik yapılmış, ikinci grup ise sağlıklı kontrol grubu olarak adlandırılmıştır. Daha sonrasında bu gruplar kendi aralarında tekrar 3 farklı gruba ayrılmış ve bu gruplaraAspartam ve Stevia günlük 250 mg/kg şeklinde verilmiş ve etkilerini karşılaştırmak için 5 hafta boyunca takip edilmiştir
Diyabetik aspartam grubu ile karşılaştırıldığında diyabetik stevia grubunun alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), kan glukoz seviyeleri ve HbA1c değerleri diyabetik aspartam grubuna göre düşük bulunmuştur (p<0,001). Stevia kontrol grubuna göre diyabetik aspartam grubunda tümör nekroz faktörü-alfa (TNF-alfa) değeri yüksek saptanmıştır (p<0,001). Sağlıklı kontrol grubuna göre, aspartam kontrol grubunun interlökin 1 (IL-1) değeri yüksek bulunmuştur (p<0,001). Diyabetik aspartam grubunun interlökin-6 (IL-6) değeri ise sağlıklı kontrol grubundan anlamlı derecede yüksek saptanmıştır (p<0,001). Diyabetik, sağlıklı kontrol ve stevia gruplarının toplam antioksidan kapasitesi (TAS), diyabetik ve kontrol aspartam gruplarından anlamlı derecede yüksek çıkmıştır (p<0,001). Diyabetik ve kontrol aspartam gruplarının toplam oksidan kapasitesi (TOS), kontrol stevia grubundan anlamlı derecede yüksek bulunmuştur (p<0,001).
Bu çalışmanın sonucuna göre aspartam ALT, AST, kan glukozu, HbA1c, TNF-alfa, IL-1, IL-6 ve TOS değerlerini steviaya göre anlamlı derecede yükseltirken, TAS değerlerini anlamlı derecede düşürmektedir.

Anahtar Kelimeler

Tatlandırıcılar, Glukoz İntoleransı, Karaciğer Enzimleri, Oksidatif Stres

Proje Numarası

47/2019-05

The Effects of Natural and Artifical Sweeteners on Glucose Intolerance, Liver Enzymes and Oxidative Stress in Rats with Type 2 Diabetes

Öz

The impacts of artificial and sweeteners on liver enzymes, glucose intolerance, and oxidative stress were investigated in the present research.
Sixty adult male Wistar rats were indiscriminately distributed to two groups, involving 30 in each. The first group was made diabetic with streptozocin, and the second group was called the healthy control group. Then, these groups were divided into 3 different groups again and these groups were given 250 mg/kg daily of Aspartame and Stevia and followed for 5 weeks to compare their effects.
A comparison between the groups indicated that the diabetic stevia group had lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood glucose, and HbA1c values than the diabetic aspartame group (p<0.001). The diabetic aspartame group had higher levels of tumor necrosis factor-alpha (TNF-alpha) value than the stevia control (p<0.001). The aspartame control group had higher levels of interleukin 1 (IL-1) than the healthy control group (p<0.001). The interleukin-6 (IL-6) value of the diabetic aspartame group was found to be noticeably higher than the healthy control group (p<0.001). The total antioxidant capacity (TAS) of the diabetic, healthy control and stevia groups was found to be considerably higher than the diabetic and control aspartame groups (p<0.001). The total oxidant capacity (TOS) of the diabetic and control aspartame groups was notably high when compared to the value of the control stevia group (p<0.001).
As a result, aspartame significantly increases AST, HbA1c, blood glucose, TNF-alpha, ALT, TOS, IL-1, and IL-6 figures compared to stevia but radically decreases TAS values.

Anahtar Kelimeler

Sweeteners, Glucose Intolerance, Liver Enzymes, Oxidative Stress

Etik Beyan

This study was conducted in accordance with the ethical rules of experimental animal studies at Gazi University Laboratory Animal Breeding and Experimental Research Center (GUDAM) after the approval of Gazi University Animal Experiments Local Ethics Committee (code number: G.U. ET-18.078)

Destekleyen Kurum

This study is supported by Gazi University Scientific Research Projects Unit

Proje Numarası

47/2019-05

Teşekkür

We would like to thank Gazi University Scientific Research Project Unit for supporting this study

Kaynakça

• 1. Kim, E, Shin, J. H, Seok, P.R, Kim, M.S, Yoo, S. H. and Kim, Y. (2018). “Phyllodulcin, a natural functional sweetener, improves diabetic metabolic changes by regulating hepatic lipogenesis, inflammation, oxidative stress, fibrosis, and gluconeogenesis in db/db mice”. Journal of Functional Foods, 42, 1-11. https://doi.org/10.1016/j.jff.2017.12.038
• 2. Khan, T. A, Ayoub-Charette, S, Sievenpiper, J. L. and Comelli, E. M. (2019).“Non-Nutritive Sweeteners and their effects on human health and the gut microbiome”. in Reference Module in Biomedical Science, 2-21. https://doi.org/10.1016/b978-0-12-801238-3.62162-1
• 3. Pepino, M. Y. (2015).“Metabolic effects of non-nutritive sweeteners”. Physiology & Behavior, 152, 450-455. https://doi.org/10.1016/j.physbeh.2015.06.024
• 4. Pepino, M. Y. and Bourne, C. (2011). “Non-nutritive sweeteners, energy balance, and glucose homeostasis”. Current Opinion in Clinical Nutrition & Metabolic Care, 14(4), 391-395. https://doi.org/10.1097/MCO.0b013e3283468e7e
• 5. Spencer, M, Gupta, A, Van Dam, L, Shannon, C, Menees, S. and Chey, W. D. (2016). “Artificial sweeteners: a systematic review and primer for gastroenterologists”. Journal of Neurogastroenterology and Motility, 22(2), 168. https://doi.org/10.5056/jnm15206
• 6. Abhilash, M, Paul, M. S, Varghese, M. V. and Nair, R. H. (2011). “Effect of long term intake of aspartame on antioxidant defense status in liver”. Food and Chemical Toxicology, 49(6), 1203-1207. https://doi.org/10.1016/j.fct.2011.02.019
• 7. Alkafafy, M. E. S, Ibrahim, Z. S, Ahmed, M. M. and El-Shazly, S. A. (2015). “Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach”. International journal of immunopathology and pharmacology, 28(2), 247-255. https://doi.org/10.1177/0394632015586134
• 8. Palmnäs, M. S, Cowan, T. E, Bomhof, M. R, Su, J, Reimer, R. A, Vogel, H. J, Hittel, D. S. and 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. https://doi.org/10.1371/journal.pone.0109841
• 9. Ashok, I, Wankhar, D, Sheeladevi, R. and Wankhar, W. (2014). “Long-term effect of aspartame on the liver antioxidant status and histopathology in Wistar albino rats”. Biomedicine & Preventive Nutrition, 4(2), 299-305. https://doi.org/10.1016/j.bionut.2013.10.002
• 10. AbdElwahab, A. H, Yousuf, A. F, Ramadan, B. K. and Elimam, H. (2017). “Comparative Effects of Stevia rebaudiana and Aspartame on hepato-renal function of diabetic rats: Biochemical and Histological Approaches”. Journal of Applied Pharmaceutical Science, 7(8), 034-042. https://doi.org/ 10.7324/JAPS.2017.70806
• 11. Othman, S. I. and Bin-Jumah, M. (2019). “Histopathological effect of aspartame on liver and kidney of mice”. International Journal of Pharmacology, 15(3), 336-342. https://doi.org/10.3923/ijp.2019.336.342
• 12. Janssens, S, Ciapaite, J, Wolters, J. C, Van Riel, N. A, Nicolay, K. and Prompers, J. J. (2017). “An in vivo magnetic resonance spectroscopy study of the effects of caloric and non-caloric sweeteners on liver lipid metabolism in rats”. Nutrients, 9(5), 476. https://doi.org/10.3390/nu9050476
• 13. Choudhary, A. K. and Devi, R. S. (2015). “Longer period of oral administration of aspartame on cytokine response in Wistar albino rats”. Endocrinología y Nutrición (English Edition), 62(3), 114-122. https://doi.org/10.1016/j.endoen.2015.02.010
• 14. Singh, S, Garg, V. and Yadav, D. (2013). “Antihyperglycemic and antioxidative ability of Stevia rebaudiana (Bertoni) leaves in diabetes induced mice”. International Journal of Pharmacy and Pharmaceutical Sciences, 5(2), 297-302.
• 15. Shivanna, N, Naika, M, Khanum, F. and Kaul, V. K. (2013). “Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana”. Journal of Diabetes and its Complications, 27(2), 103-113. https://doi.org/10.1016/j.jdiacomp.2012.10.001
• 16. Akbarzadeh, S, Eskandari, F, Tangestani, H, Bagherinejad, S. T, Bargahi, A, Bazzi, P, Daneshi, A, Sahrapoor, A, O'Connor, W. J. and Rahbar, A. R. (2015). “ The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ-induced diabetic rats”. Journal of Dietary Supplements, 12(1), 11-22. https://doi.org/10.3109/19390211.2014.901999
• 17. Latha, S, Chaudhary, S. and Ray, R. S. (2017). “Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats”. Biomedicine & Pharmacotherapy, 95, 1040-1050. https://doi.org/10.1016/j.biopha.2017.08.082
• 18. European Food Safety Authority (2019). Aspartame Web: https://www.efsa.europa.eu/en/topics/topic/aspartame. Retrieved from the address on 16.07.2019.
• 19. World Health Organization (2019). Web: http://apps.who.int/food-additivescontaminants-jecfa/database/chemical.aspx?chemID=62. Retrieved from the address on 16.07.2019.
• 20. Nair, A. B. and Jacob, S. (2016). “A simple practice guide for dose conversion between animals and human”. Journal of Basic and Clinical Pharmacy, 7, 27-31. https://doi.org/10.4103/0976-0105.177703
• 21. Erel, O. (2004). “A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation”. Clinical Biochemistry, 37(4), 277-285. https://doi.org/10.1016/j.clinbiochem.2003.11.015
• 22. Erel, O. (2005). “A new automated colorimetric method for measuring total oxidant status”. Clinical Biochemistry, 38(12), 1103-1111. https://doi.org/10.1016/j.clinbiochem.2005.08.008
• 23. Kılıç, E, Toprak, A. E, Ayhan, S. K, Alper, B. A. Ş. and Duruyen, S. (2015). “Şizofrenik hastaların atak ve remisyon dönemlerinde oksidatif stress”. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi, 7(4), 286-298.
• 24. Lebda, M. A, Tohamy, H. G. and El-Sayed, Y. S. (2017). “Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status”. Nutrition Research, 41, 47-55. https://doi.org/10.1016/j.nutres.2017.04.002
• 25. Elnaga, N. A, Massoud, M. I, Yousef, M. I. and Mohamed, H. H. (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 Sciences, 61(1), 155-163. https://doi.org/doi: 10.1016/j.aoas.2015.11.008
• 26. Holvoet, P, Rull, A, García-Heredia, A, López-Sanromà, S, Geeraert, B, Joven, J. and Camps, J. (2015). “Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study”. Food and Chemical Toxicology, 77, 22-33. https://doi.org/10.1016/j.fct.2014.12.017
• 27. Rotimi, S. O, Rotimi, O. A, Adelani, I. B, Onuzulu, C, Obi, P. and Okungbaye, R. (2018). “Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats”. Heliyon, 4(5). https://doi.org/10.1016/j.heliyon.2018.e00640
• 28. Sharma, R, Yadav, R. and Manivannan, E. (2012). “Study of effect of Stevia rebaudiana bertoni on oxidative stress in type-2 diabetic rat models”. Biomedicine & Aging Pathology, 2(3), 126-131. https://doi.org/10.1016/j.biomag.2012.07.001
• 29. Ilić, V, Vukmirović, S, Stilinović, N, Čapo, I, Arsenović, M. and Milijašević, B. (2017). “Insight into anti-diabetic effect of low dose of stevioside”. Biomedicine & Pharmacotherapy, 90, 216-221. https://doi.org/10.1016/j.biopha.2017.03.045
• 30. Food and Agriculture Organization (2022). Steviol Glycosides from Stevia rebaudiana Bertoni [online]. Website https://www.fao.org/3/BU297en/bu297en.pdf [accessed 04.11.2022].
• 31. Ahmad, U. and Ahmad, R. S. (2018). “Anti diabetic property of aqueous extract of Stevia rebaudiana Bertoni leaves in Streptozotocin-induced diabetes in albino rats”. BMC complementary and alternative medicine, 18, 1-11. https://doi.org/10.1186/s12906-018-2245-2
• 32. Choudhary, A. K. and Devi, R. S. (2014). Serum biochemical responses under oxidative stress of aspartame in wistar albino rats”. Asian Pacific Journal of Tropical Disease, 4, S403-S410. https://doi.org/10.1016/S2222-1808(14)60478-3
• 33. Finamor, I, Pérez, S, Bressan, C. A, Brenner, C. E, Rius-Pérez, S, Brittes, P. C, Cheiran, G, Rocha, M. I, da Veiga, M, Sastre, J. and Pavanato, M. A. (2017). “Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice”. Redox Biology, 11, 701-707. https://doi.org/10.1016/j.redox.2017.01.019
• 34. Ramos-Tovar, E, Flores-Beltrán, R. E, Galindo-Gómez, S, Camacho, J, Tsutsumi, V. and Muriel, P. (2019). “An aqueous extract of Stevia rebaudiana variety Morita II prevents liver damage in a rat model of cirrhosis that mimics the human disease”. Annals of Hepatology, 18(3), 472-479. https://doi.org/10.1016/j.aohep.2018.10.002
• 35. Ashok, I, & Sheeladevi, R. (2015).“Oxidant stress evoked damage in rat hepatocyte leading to triggered nitric oxide synthase (NOS) levels on long term consumption of aspartame. Journal of Food and Drug Analysis, 23(4), 679-691. https://doi.org/10.1016/j.jfda.2014.07.011
• 36. Saleh, A. A. S. (2015). “Anti-neuroinflammatory and antioxidant effects of N-acetyl cysteine in long-term consumption of artificial sweetener aspartame in the rat cerebral cortex”. The Journal of Basic & Applied Zoology, 72, 73-80. https://doi.org/10.1016/j.jobaz.2015.05.001
• 37. Ramos-Tovar, E. and Muriel, P. (2019). “Phytotherapy for the liver”. In Dietary interventions in liver disease (pp. 101-121). Academic Press. https://doi.org/10.1016/B978-0-12-814466-4.00009-4
• 38. .Boonkaewwan, C, Toskulkao, C. and Vongsakul, M. (2006). “Anti-inflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells”. Journal of Agricultural and Food Chemistry, 54(3), 785-789. https://doi.org/10.1021/jf0523465
• 39. Onaolapo, A. Y, Abdusalam, S. Z. and Onaolapo, O. J. (2017). “Silymarin attenuates aspartame-induced variation in mouse behaviour, cerebrocortical morphology and oxidative stress markers”. Pathophysiology, 24(2), 51-62. https://doi.org/10.1016/j.pathophys.2017.01.002
• 40. Alavala, S, Sangaraju, R, Nalban, N, Sahu, B. D, Jerald, M. K, Kilari, E. K. and Sistla, R. (2019). “Stevioside, a diterpenoid glycoside, shows anti-inflammatory property against Dextran Sulphate Sodium-induced ulcerative colitis in mice”. European Journal of Pharmacology, 855, 192-201. https://doi.org/10.1016/j.ejphar.2019.05.015