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Year 2021, Volume: 25 Issue: 2, 117 - 123, 27.06.2025

Saida Ibragić Emir Fehratović Damir Suljevic , Maja Mitrašinović-brulić

https://doi.org/10.29228/jrp.2
Cited By: 1

Abstract

References

  • [1] World Health Organization, 2015. WHO calls on countries to reduce sugars intake among adults and children. Press release. https://www.who.int/mediacentre/news/releases/2015/sugar-guideline/en/ (accessed March 2019).
  • [2] Mortensen A. Sweeteners permitted in the European Union: safety aspects. Food Nutr Res. 2006;50(3):104-116. [CrossRef]
  • [3] Bopp BA, Sonders RC, Kesterson JW, Renwick AG. Toxicological aspects of cyclamate and cyclohexylamine. Critical Rev Toxicol. 1986; 16(3): 213-306. [CrossRef]
  • [4] Renwick AG, Thompson JP, O'shaughnessy M, Walter EJ. The metabolism of cyclamate to cyclohexylamine in humans during long-term administration. Toxicol Appl Pharmacol. 2004; 196(3): 367-380. [CrossRef]
  • [5] Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners–a review. J Food Sci Technol. 2014; 51(4):611-621.[CrossRef]
  • [6] Taylor JD, Richards RK, Wiegand RG, Weinberg MS. Toxicological studies with sodium cyclamate and saccharin. Food Cosmetics Toxicol. 1968; 6(3): 313-327. [CrossRef]
  • [7] Brantom PG, Gaunt IF, Grasso P. Long-term toxicity of sodium cyclamate in mice. Food Cosmetics Toxicol. 1973;11(4): 735-746. [CrossRef]
  • [8] Amin KA, AlMuzafar HM. Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharine and methyl-salicylates. Int J Clin Exp Med. 2015; 6133-6144.
  • [9] Adaramoye OA, Akanni OO. Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats. J Basic Clin Physiol Pharmacol. 2016; 27(1): 29-37. [CrossRef]
  • [10] Ashok I, Poornima PS, Wankhar D, Ravindran R, Sheeladevi R. Oxidative stress evoked damages on rat sperm and attenuated antioxidant status on consumption of aspartame. Int J Impot Res. 2017; 29(4): 164-170. [CrossRef]
  • [11] Lebda MA, Sadek KM, El-Sayed YS. Aspartame and soft drink-mediated neurotoxicity in rats: implication of oxidative stress, apoptotic signaling pathways, electrolytes and hormonal levels. Metab Brain Dis. 2017; 32(5): 1639-1647.[CrossRef]
  • [12] Polyák É, Gombos K, Hajnal B, Bonyár-Müller K, Szabó S, Gubicskó-Kisbenedek A, Marton K, Ember I. Effects of artificial sweeteners on body weight, food and drink intake. Acta Physiol Hung. 2010; 97(4): 401-407. [CrossRef]
  • [13] Abdelaziz I, Ashour AERA. Effect of saccharin on albino rats’ blood indices and the therapeutic action of vitamins C and E. Hum Exp Toxicol. 2011; 30(2): 129-137. [CrossRef]
  • [14] Butterfield DA, Stadtman ER. Protein oxidation processes in aging brain. In: Advances in cell aging and grontology, Elsevier. 1997; 2: 161-191. [CrossRef]
  • [15] Mourad IM, Noor NA. Aspartame (a widely used artificial sweetener) and oxidative stress in the rat cerebral cortex. Int J Pharmd Biomed Sci. 2011; 2(1): 4-10.
  • [16] Dhabhar FS, McEwen BS. Biodirectional effects of stress and glucocorticoid hormones on immune function: Possible explanations for paradoxical observations, In: Ader, R., Felten, D.L. and Cohen, N. (Eds.). Psychoneuroimmunology. San Diego, CA: Academic Press. 2001: 301–338.
  • [17] Abdallah IZ. Physiological changes induced by long term administration of saccharin compared with aspartame to male albino rats. Egyptian J Hosp Med. 2002; 8(1): 70-81. [CrossRef]
  • [18] Naik AQ, Shrivastava VK. Effects of short-term consumption of aspartame on some biochemical and hematological parameters in female swiss albino mice. Int J Zoo Res. 2019; 15: :21-27. [CrossRef]
  • [19] Abu-Taweel GM. Effects of curcumin on the social behavior, blood composition, reproductive hormones in plasma and brain acetylcholinesterase in cadmium intoxicated mice. Saudi J Biol Sci. 2016; 23(2): 219-228. [CrossRef]
  • [20] Iroghama AA, Awo OM, Iwamo O. Haematological and haemostatic effects of aspartame and saccharin in albino Wistar rats. J Sci Technol. 2017; 3: 14-2.
  • [21] Jin Y, Zhang X, Shu L, Chen L, Sun L, Qian H, Liu W, Fu Z. Oxidative stress response and gene expression with atrazine exposure in adult female zebrafish (Danio rerio). Chemosphere. 2010; 78(7): 846-852. [CrossRef]
  • [22] Weydert CJ, Cullen JJ. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature protocols. 2010; 5(1): 51-66. [CrossRef]
  • [23] ElTerras A, Soliman MM, Alkhedaide A, Attia HF, Alharthy A, Banaja AE. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats. Mol Med Reports. 2016; 13(4): 3147-3154.[CrossRef]
  • [24] Directive C. 86/609/EEC. On the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official J Europ Comm. 1986; 29: 358.
  • [25] Rogers PJ, Hogenkamp PS, De Graaf C, Higgs S, Lluch A, Ness AR, Penfold C, Perry R, Putz P, Yeomans MR, Mela DJ. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes. 2016; 40(3): 381-394. [CrossRef]
  • [26] Suljevic D, Hamzic A, Focak M, Zahirovic A, Alijagic A. Morphological and cytochemical characterization of the sternal leukopoietic cell lineages in wistar rat. Int J Fauna Biol Stud. 2017; 4(5): 99-103.
  • [27] Balasubramaniam P, Malathi A. Comparative study of hemoglobin estimated by Drabkin’s and Sahli’smethods. J Postgrad Med. 1992; 38: 8–9.
  • [28] Aebi H. Catalase in vitro. In: Methods in enzymology. Elsevier, Academic Press.1984; 105: 121-126. [CrossRef]

Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C

Year 2021, Volume: 25 Issue: 2, 117 - 123, 27.06.2025

Saida Ibragić Emir Fehratović Damir Suljevic , Maja Mitrašinović-brulić

https://doi.org/10.29228/jrp.2
Cited By: 1

Abstract

The aim of this study was to evaluate the effects of sodium cyclamate and saccharine combination on the overall hematological parameters and brain catalase activity in Wistar rats. During a period of 8 weeks, the animals were given the artificial sweeteners in a low (L; 15,4 mg/mL) and high dose (H; 22 mg/mL). Additionally, to determine whether vitamin C can attenuate the changes induced by high doses, it was administered to a third group of animals (H + vit C; 22 mg/mL+25 mg/mL). Decreased hematocrit and hemoglobin values, low erythrocyte count and mean cell volume in the groups treated with the artificial sweeteners were the main hematological changes causing microcytic anemia. Catalase activity in brain tissue decreased with the increase of the sweeteners dose, which clearly indicates the induction of oxidative stress. Further on, catalase was significantly increased in the H + vit C group compared to the H group but there was no significant difference compared to controls. Collectively, these results suggest that sodium cyclamate and saccharine induced considerable alterations in the hematology, an increased consumption of catalase and a high efficiency of vitamin C to ameliorate the oxidative stress.

Keywords

Mamamlian model catalase activity blood cyclamates saccharine ascorbic acid

References

  • [1] World Health Organization, 2015. WHO calls on countries to reduce sugars intake among adults and children. Press release. https://www.who.int/mediacentre/news/releases/2015/sugar-guideline/en/ (accessed March 2019).
  • [2] Mortensen A. Sweeteners permitted in the European Union: safety aspects. Food Nutr Res. 2006;50(3):104-116. [CrossRef]
  • [3] Bopp BA, Sonders RC, Kesterson JW, Renwick AG. Toxicological aspects of cyclamate and cyclohexylamine. Critical Rev Toxicol. 1986; 16(3): 213-306. [CrossRef]
  • [4] Renwick AG, Thompson JP, O'shaughnessy M, Walter EJ. The metabolism of cyclamate to cyclohexylamine in humans during long-term administration. Toxicol Appl Pharmacol. 2004; 196(3): 367-380. [CrossRef]
  • [5] Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners–a review. J Food Sci Technol. 2014; 51(4):611-621.[CrossRef]
  • [6] Taylor JD, Richards RK, Wiegand RG, Weinberg MS. Toxicological studies with sodium cyclamate and saccharin. Food Cosmetics Toxicol. 1968; 6(3): 313-327. [CrossRef]
  • [7] Brantom PG, Gaunt IF, Grasso P. Long-term toxicity of sodium cyclamate in mice. Food Cosmetics Toxicol. 1973;11(4): 735-746. [CrossRef]
  • [8] Amin KA, AlMuzafar HM. Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharine and methyl-salicylates. Int J Clin Exp Med. 2015; 6133-6144.
  • [9] Adaramoye OA, Akanni OO. Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats. J Basic Clin Physiol Pharmacol. 2016; 27(1): 29-37. [CrossRef]
  • [10] Ashok I, Poornima PS, Wankhar D, Ravindran R, Sheeladevi R. Oxidative stress evoked damages on rat sperm and attenuated antioxidant status on consumption of aspartame. Int J Impot Res. 2017; 29(4): 164-170. [CrossRef]
  • [11] Lebda MA, Sadek KM, El-Sayed YS. Aspartame and soft drink-mediated neurotoxicity in rats: implication of oxidative stress, apoptotic signaling pathways, electrolytes and hormonal levels. Metab Brain Dis. 2017; 32(5): 1639-1647.[CrossRef]
  • [12] Polyák É, Gombos K, Hajnal B, Bonyár-Müller K, Szabó S, Gubicskó-Kisbenedek A, Marton K, Ember I. Effects of artificial sweeteners on body weight, food and drink intake. Acta Physiol Hung. 2010; 97(4): 401-407. [CrossRef]
  • [13] Abdelaziz I, Ashour AERA. Effect of saccharin on albino rats’ blood indices and the therapeutic action of vitamins C and E. Hum Exp Toxicol. 2011; 30(2): 129-137. [CrossRef]
  • [14] Butterfield DA, Stadtman ER. Protein oxidation processes in aging brain. In: Advances in cell aging and grontology, Elsevier. 1997; 2: 161-191. [CrossRef]
  • [15] Mourad IM, Noor NA. Aspartame (a widely used artificial sweetener) and oxidative stress in the rat cerebral cortex. Int J Pharmd Biomed Sci. 2011; 2(1): 4-10.
  • [16] Dhabhar FS, McEwen BS. Biodirectional effects of stress and glucocorticoid hormones on immune function: Possible explanations for paradoxical observations, In: Ader, R., Felten, D.L. and Cohen, N. (Eds.). Psychoneuroimmunology. San Diego, CA: Academic Press. 2001: 301–338.
  • [17] Abdallah IZ. Physiological changes induced by long term administration of saccharin compared with aspartame to male albino rats. Egyptian J Hosp Med. 2002; 8(1): 70-81. [CrossRef]
  • [18] Naik AQ, Shrivastava VK. Effects of short-term consumption of aspartame on some biochemical and hematological parameters in female swiss albino mice. Int J Zoo Res. 2019; 15: :21-27. [CrossRef]
  • [19] Abu-Taweel GM. Effects of curcumin on the social behavior, blood composition, reproductive hormones in plasma and brain acetylcholinesterase in cadmium intoxicated mice. Saudi J Biol Sci. 2016; 23(2): 219-228. [CrossRef]
  • [20] Iroghama AA, Awo OM, Iwamo O. Haematological and haemostatic effects of aspartame and saccharin in albino Wistar rats. J Sci Technol. 2017; 3: 14-2.
  • [21] Jin Y, Zhang X, Shu L, Chen L, Sun L, Qian H, Liu W, Fu Z. Oxidative stress response and gene expression with atrazine exposure in adult female zebrafish (Danio rerio). Chemosphere. 2010; 78(7): 846-852. [CrossRef]
  • [22] Weydert CJ, Cullen JJ. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature protocols. 2010; 5(1): 51-66. [CrossRef]
  • [23] ElTerras A, Soliman MM, Alkhedaide A, Attia HF, Alharthy A, Banaja AE. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats. Mol Med Reports. 2016; 13(4): 3147-3154.[CrossRef]
  • [24] Directive C. 86/609/EEC. On the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official J Europ Comm. 1986; 29: 358.
  • [25] Rogers PJ, Hogenkamp PS, De Graaf C, Higgs S, Lluch A, Ness AR, Penfold C, Perry R, Putz P, Yeomans MR, Mela DJ. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes. 2016; 40(3): 381-394. [CrossRef]
  • [26] Suljevic D, Hamzic A, Focak M, Zahirovic A, Alijagic A. Morphological and cytochemical characterization of the sternal leukopoietic cell lineages in wistar rat. Int J Fauna Biol Stud. 2017; 4(5): 99-103.
  • [27] Balasubramaniam P, Malathi A. Comparative study of hemoglobin estimated by Drabkin’s and Sahli’smethods. J Postgrad Med. 1992; 38: 8–9.
  • [28] Aebi H. Catalase in vitro. In: Methods in enzymology. Elsevier, Academic Press.1984; 105: 121-126. [CrossRef]
There are 28 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Saida Ibragić

Emir Fehratović

Damir Suljevic

Maja Mitrašinović-brulić

Publication Date June 27, 2025
Published in Issue Year 2021 Volume: 25 Issue: 2

Cite

APA Ibragić, S., Fehratović, E., Suljevic, D., Mitrašinović-brulić, M. (2025). Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C. Journal of Research in Pharmacy, 25(2), 117-123. https://doi.org/10.29228/jrp.2
AMA Ibragić S, Fehratović E, Suljevic D, Mitrašinović-brulić M. Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C. J. Res. Pharm. June 2025;25(2):117-123. doi:10.29228/jrp.2
Chicago Ibragić, Saida, Emir Fehratović, Damir Suljevic, and Maja Mitrašinović-brulić. “Artificial Sweeteners Elicit Oxidative Stress in Rat Brain and Development of Microcytic Anemia: Promising Protective Effects of Vitamin C”. Journal of Research in Pharmacy 25, no. 2 (June 2025): 117-23. https://doi.org/10.29228/jrp.2.
EndNote Ibragić S, Fehratović E, Suljevic D, Mitrašinović-brulić M (June 1, 2025) Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C. Journal of Research in Pharmacy 25 2 117–123.
IEEE S. Ibragić, E. Fehratović, D. Suljevic, and M. Mitrašinović-brulić, “Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C”, J. Res. Pharm., vol. 25, no. 2, pp. 117–123, 2025, doi: 10.29228/jrp.2.
ISNAD Ibragić, Saida et al. “Artificial Sweeteners Elicit Oxidative Stress in Rat Brain and Development of Microcytic Anemia: Promising Protective Effects of Vitamin C”. Journal of Research in Pharmacy 25/2 (June 2025), 117-123. https://doi.org/10.29228/jrp.2.
JAMA Ibragić S, Fehratović E, Suljevic D, Mitrašinović-brulić M. Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C. J. Res. Pharm. 2025;25:117–123.
MLA Ibragić, Saida et al. “Artificial Sweeteners Elicit Oxidative Stress in Rat Brain and Development of Microcytic Anemia: Promising Protective Effects of Vitamin C”. Journal of Research in Pharmacy, vol. 25, no. 2, 2025, pp. 117-23, doi:10.29228/jrp.2.
Vancouver Ibragić S, Fehratović E, Suljevic D, Mitrašinović-brulić M. Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C. J. Res. Pharm. 2025;25(2):117-23.

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