The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study
Al-Moatasem, M., Abdelaziz Helmy, D., Mostafa, S., Gaeidy, A. (2024). The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study. EKB Journal Management System, 2(1), 58-91. doi: 10.21608/ejctr.2024.259445.1011
Mai Amin Al-Moatasem; Dalia Hussein Abdelaziz Helmy; Salwa Khaled Mostafa; Amira Shaban Gaeidy. "The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study". EKB Journal Management System, 2, 1, 2024, 58-91. doi: 10.21608/ejctr.2024.259445.1011
Al-Moatasem, M., Abdelaziz Helmy, D., Mostafa, S., Gaeidy, A. (2024). 'The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study', EKB Journal Management System, 2(1), pp. 58-91. doi: 10.21608/ejctr.2024.259445.1011
Al-Moatasem, M., Abdelaziz Helmy, D., Mostafa, S., Gaeidy, A. The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study. EKB Journal Management System, 2024; 2(1): 58-91. doi: 10.21608/ejctr.2024.259445.1011

The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study

Egyptian Journal of Cell and Tissue Research
Volume 2, Issue 1, January 2024, Page 58-91  XML PDF (2.03 MB)
Document Type: Original articles
DOI: 10.21608/ejctr.2024.259445.1011
View on SCiNiTO View on SCiNiTO
Authors
Mai Amin Al-Moatasem1; Dalia Hussein Abdelaziz Helmy2; Salwa Khaled Mostafa email 3; Amira Shaban Gaeidy1
1Lecturer of Medical Histology & Cell Biology, Faculty of Medicine, Beni-Suef University
2Professor of Medical Histology & Cell Biology, Faculty of Medicine, Beni-Suef University
3Demonstrator of Medical Histology & Cell Biology, Faculty of Medicine, Beni-suef University
Abstract
Background:Aspartame is widely consumed worldwide. Its metabolites can be toxic to various body organs. L-Arginineis widely available in daily food products and it has an antioxidant property. Aim:This study was done to evaluate the protective effect of L-arginine on aspartame treated adrenal gland in a rat model using histological, immunohistochemical, biochemical, and morphometric studies. Material and Methods: Fifty adult male albino rats five-sixmonthold, weighing180-200 grams were used. They were divided into five groups. Group I(Control). Group II(L-arginine): each rat received 0.3mg/ gm/dayfor 4 weeks. Group III (Aspartame group): each rat received 250mg/Kg/day for 4 weeks. Group IV (Aspartame+L-arginine treated group) each rat received L-arginine & aspartame as in groups II & III respectively.  Group V (Recovery group): each rat received aspartame as in group III, then, rats were left for another 4 weeksbefore they were sacrificed. Adrenal glands were dissected and subjected to Hematoxylin&Eosin andMasson’s Trichromestains, Caspase-3, biochemical and morphometric studies.  Results: In aspartame group, the adrenal cortex revealed decreased capsular thicknesswith complete shedding in some areas byMasson’s Trichrome,disorganization of the cellular arrangement in adrenal cortex.Some cells revealed vacuolated cytoplasm, others appeared with pyknotic nuclei by Hematoxylin&Eosin.ACTH, cortisol, aldosterone, and MDA concentrations were significantly increased while GSH concentration was significantly decreased in aspartame group. Aspartame group showed significant increase in positive immunoreactivity for Caspase-3, compared to other groups. L-arginine treatment improved the histological, immunohistochemical, biochemical, and morphometric results. Recovery group (V) revealed incomplete improvement.  Conclusion: L-arginineprotects the adrenal cortex from the aspartame induced toxicity inadult male albino rats.
Keywords
Adrenal Cortex; L-arginine; Aspartame; immunohistochemistry; Biochemistry
References

  1. Mahar, Y., Qamar, A., Hidayat, M., Salman, S., Chaudhry, S., & Saeeduddin, M. F. (2021). Effect Of L-Arginine And Insulin On Adrenal Gland Damaged By Streptozotocin In Albino Rats. Journal of Ayub Medical College, Abbottabad: JAMC, 33(1): 134-138.
  2. Getabalew, M., Alemneh, T., & Zewdie, D. (2020).Review on hormonal metabolic adaptations of farm animals. stress, 8(9): 1037–1042.
  3. Olukole, S. G., Lanipekun, D. O., Ola-Davies, E. O., & Oke, B. O. (2019).Melatonin attenuates bisphenol A-induced toxicity of the adrenal gland of Wistar rats. Environmental Science and Pollution Research, 26, 5971-5982.
  4. Anbara, H., Sheibani, M. T., & Razi, M. (2020). Long-term effect of aspartame on male reproductive system: Evidence for testicular histomorphometrics, Hsp70-2 protein expression and biochemical status. International journal of fertility & sterility, 14(2), 91-101.
  5. Czarnecka, K., Pilarz, A., Rogut, A., Maj, P., Szymańska, J., Olejnik, Ł., & Szymański, P. (2021). Aspartame—true or false? Narrative review of safety analysis of general use in products. Nutrients, 13(6), 1957-1974.
  6. Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020).Oxidative stress in cancer. Cancer cell, 38(2), 167-197.
  7. Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., ... & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical interventions in aging, 13, 757-772.
  8. Vona, R., Gambardella, L., Cittadini, C., Straface, E., & Pietraforte, D. (2019). Biomarkers of oxidative stress in metabolic syndrome and associated diseases. Oxidative medicine and cellular longevity, 2019: 1-19.
  9. Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of toxicology, 94(3), 651-715.
  10. Zhang, P., Li, T., Wu, X., Nice, E. C., Huang, C., & Zhang, Y. (2020).Oxidative stress and diabetes: antioxidative strategies. Frontiers of medicine, 14, 583-600.
  11. Ross Phan, P. (2023).L-arginine: Uses, side effects, and more, Very well Health. Available at: https://www.verywellhealth.com/using-l-arginine-for-health-88322 (Accessed: 15 January 2024).
  12. Elbassuoni, E. A., Ragy, M. M., & Ahmed, S. M. (2018). Evidence of the protective effect of l-arginine and vitamin D against monosodium glutamate-induced liver and kidney dysfunction in rats. Biomedicine & pharmacotherapy, 108: 799–808.
  13. Abdel Malak, H. W., & Amin, M. A. (2018). Protective Role of L-arginine on the Suprarenal Gland of Adult Male Albino Rats Subjected to Recurrent Acute Restraint Stress: A Histological and Immunohistochemical Study. The Egyptian Journal of Anatomy, 41(1), 156-171.
  14. Abdelhaliem, N. G., & Mohamed, D. S. (2017).Comparative Study on The Safety of Aspartame and Stevia on The Adrenal-Pituitary Axis of Adult Male Albino Rats: Histological and Immunohistochemical Study. Egyptian Journal of Histology, 40(2), 216-225.
  15. Bekheet, E. A., & Rady, H. Y. (2020). Neurotoxic effect of aspartame on the sciatic nerve of adult male albino rat and the possibility of spontaneous recovery: light and electron microscopic study. Ain Shams Medical Journal, 71(1), 15-30.
  16. Suvarna, K. S., Layton, C., & Bancroft, J. D. (2018).Bancroft's theory and practice of histological techniques, 8th edition. Chapter 9,Elsevier Health Sciences Publishing(pp. 126-138).
  17. Suvarna, K. S., Layton, C., & Bancroft, J. D. (Eds.). (2018). Bancroft's theory and practice of histological techniques E-Book, 8th edition, Chapter 19, Elsevier Health Sciences Publishing(pp. 337-394).
  18. Shalaby, A. M., Aboregela, A. M., Alabiad, M. A., & El Shaer, D. F. (2020). Tramadol promotes oxidative stress, fibrosis, apoptosis, ultrastructural and biochemical alterations in the adrenal cortex of adult male rat with possible reversibilityafter withdrawal. Microscopy and Microanalysis, 26(3), 509-523.
  19. Griebsch, L. V., Theiss, E. L., Janitschke, D., Erhardt, V. K. J., Erhardt, T., Haas, E. C., ... & Grimm, H. S. (2023). Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells. Nutrients, 15(6), 1467.
  20. Hassen, E. Z., Ibrahem, N. E., & El-Shal, A. S. (2019).The Effect of Long Term Administration of Aspartame on the Sciatic nerve of adult male albino rats and the Possible Therapeutic Role of Ozone (Histological and Biochemical Study). Egyptian Journal of Histology, 42(1), 191-201.
  21. EL Tahawy, N. F. G., & Abozaid, S. M. M. (2019).The possible structural changes in the adrenal gland cortex after induction of hepatic ischemia–reperfusion injury in male albino rats: Light and electron microscopic study. Journal of Cellular Physiology, 234(9), 15487-15495.
  22. Umbayev, B., Askarova, S., Almabayeva, A., Saliev, T., Masoud, A. R., & Bulanin, D. (2020). Galactose-induced skin aging: the role of oxidative stress. Oxidative Medicine and Cellular Longevity, 2020,1-15.
  23. Abdel-ghaffar, S. K., Adly, M. A., El-Sayed, M. F., & Abd-Elsamei, W. M. (2021). Protective effects of some antioxidants against long-term intake of aspartame toxicity on liver and kidney: biochemical and histopathological approach in rats. The Journal of Basic and Applied Zoology, 82(1), 1-9.
  24. Azez, O. H., Baker, S. A., Abdullah, M. A., & Nabi, R. K. (2023).Histopathological and the Dose Depended Effects of Aspartame toxicity on Liver and Kidney of Rats. Journal of Applied Veterinary Sciences, 8(2), 16-22.
  25. Sadek, M. T., El-Abd, S. S., & Ibrahim, M. A. (2020). Effect of Chronic Unpredictable Mild Stress on Adrenal Cortex of Adult Rat and The Possible Protective Role of Licorice Extract: A Histological and Immunohistochemical study. Egyptian Journal of Histology, 44(4), 887-901.
  26. Ali, O. S. M., Amin, N. E. D., Abdel Fattah, S. M., & Abd El-Rahman, O. (2020).Ameliorative effect of kefir against γ-irradiation induced liver injury in male rats: Impact on oxidative stress and inflammation. Environmental Science and Pollution Research, 27, 35161-35173.
  27. Vural, P., Kabaca, G., Firat, R. D., & Degirmecioglu, S. (2017). Administration of selenium decreases lipid peroxidation and increases vascular endothelial growth factor in streptozotocin induced diabetes mellitus. Cell Journal (Yakhteh), 19(3), 452.
  28. Ito, F., Sono, Y., & Ito, T. (2019). Measurement and clinical significance of lipid peroxidation as a biomarker of oxidative stress: oxidative stress in diabetes, atherosclerosis, and chronic inflammation. Antioxidants, 8(3): 72-100.
  29. Moftah, O. M. Y., Gadallah, A. A., Elemam, S. I. A., & El-Sayyad, H. I. H. (2020). Impairment of Hepatic, Cardiac and Lung Tissues in Aspartame Treated Male Wistar Albino Rats. East African Scholars Journal of Medical Sciences, (3)2: 41-46.
  30. El Haliem, N. G., & Mohamed, D. S. (2011). The effect of aspartame on the histological structure of the liver and renal cortex of adult male albino rat and the possible protective effect of Pimpinella anisum oil. Egyptian Journal of Histology, 34(4), 715-726.
  31. Morovvati, H., Anbara, H., Sheibani, M. T., Koohi, M. K., & Hasanzadeh, A. (2019). The effect of long-term exposure to aspartame on histomorphometric and histochemical adrenal gland in adult NMRI mice. Armaghane Danesh, 24(2): 150-169.
  32. Guo, Y., Zhang, L., Yao, X., Tong, R., Cheng, C., Zhang, T., Wang, S., & Yang, H. G. (2019).Effects of nitric oxide on steroidogenesis and apoptosis in goat luteinized granulosa cells. Theriogenology, 126: 55-62.
  33. Ali, A. F., & Badawy Khair, N. S. (2023).Effect of induced hepatic ischemia–reperfusion on the adrenal cortex of adult male albino rats and the possible protective role of L-arginine: Biochemical, histological and immunohistochemial study. Egyptian Journal of Histology, 46(1), 206-220.
  34. McKay, T. B., Priyadarsini, S., Rowsey, T., & Karamichos, D. (2021). Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus. Cells, 10 (8): 2076-2088.
  35. Attia, H., Fadda, L., Al-Rasheed, N., Al-Rasheed, N., & Maysarah, N. (2020). Carnosine and l-arginine attenuate the downregulation of brain monoamines and gamma aminobutyric acid; reverse apoptosis and upregulate the expression of angiogenic factors in a model of hemic hypoxia in rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 393(3): 381-394.
  36. Darband, G., Sadighparvar, S., Yousefi, B., Kaviani, M., Mobaraki, K., & Majidinia, M. (2020). Combination of exercise training and L-arginine reverses aging process through suppression of oxidative stress, inflammation, and apoptosis in the rat heart. Pflügers Archiv-European Journal of Physiology, 472(2): 169-178.
  37. Anbara, H., Kian, M., Darya, G. H., & Sheibani, M. T. (2022).Longterm intake of aspartameinduced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53dependent apoptosis in a mouse model. International Journal of Experimental Pathology, 103(6): 252-262.
  38. Jan, R. (2019). Understanding apoptosis and apoptotic pathways targeted cancer therapeutics. Advanced pharmaceutical bulletin, 9(2): 205-219.
  39. Finco, I., Mohan, D. R., Hammer, G. D., & Lerario, A. M. (2019). Regulation of stem and progenitor cells in the adrenal cortex. Current opinion in endocrine and metabolic research, 8: 66-71.
  40. Ali, W. A. G., Mohammed, S. A., Abdullah, E. M., & Salah ElDeen, E. M. (2019). Aspartame: basic information for toxicologists. Sohag Medical Journal, 23(2): 47-51.
  41. Karpets, Y. V., Kolupaev, Y. E., & Shkliarevskyi, M. A. (2021).Functional interaction of hydrogen sulfide with nitric oxide, calcium, and reactive oxygen species under abiotic stress in plants. Hydrogen Sulfide and Plant Acclimation to Abiotic Stresses,2021(1): 31-57.
  42. He, H., Oo, T. L., Huang, W., He, L. F., & Gu, M. (2019). Nitric oxide acts as an antioxidant and inhibits programmed cell death induced by aluminum in the root tips of peanut (Arachis hypogaea L.). Scientific Reports, 9(1): 1-12.
  43. Egbuonu, A. C. C., & Elendu, D. S. (2021).Alterations in brain histomorphology and some homogenate antioxidant bio-pointers in L-arginine co-exposed aspartame assaulted rats. Animal Research International, 18(2): 4116-4124.
  44. Enciu, R. R., Trus, C., & Ungurianu, S. (2020). Aspartame Consumption Increases Glutathione Peroxidase Level and Depression-Like Behavior in Rats.  CHIM, 71: 247-253.
  45. Choudhary, A. K., & Lee, Y. Y. (2018). Neurophysiological symptoms and aspartame: What is the connection?. Nutritional neuroscience,21(5): 306-316.
  46. Collison, K. S., Inglis, A., Shibin, S., Saleh, S., Andres, B., Ubungen, R., Thiam, J., Mata, P., & Al-Mohanna, F. (2018). Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression. PloS one, 13(3): e0194416-e0194447.
  47. Clark, K. A., Jacob, E. B., MohanKumar, P. S., & MohanKumar, S. M. (2019). Leptin and HPA axis activity in diabetic rats: effects of adrenergic agonists. Brain Research, 1707: 54-61.
  48. Herman, O. M., Herasymiuk, I. Y., & Fedoniuk, L. Y. (2021). Character and specifics of the structural alteration of the parenchyma and bloodstream of the testes of white rats with prolonged administration of high doses of prednisolone. Wiad Lek, 74(12): 3147-3151.
  49. Yang, J. Y., Zhang, Y. F., Li, Y. X., Meng, X. P., & Bao, J. F. (2018). l-arginine protects against oxidative damage induced by T-2 toxin in mouse Leydig cells. Journal of biochemical and molecular toxicology, 32(10): e22209-e22217.
  50. Touyz, R. M., Rios, F. J., Alves-Lopes, R., Neves, K. B., Camargo, L. L., & Montezano, A. C. (2020). Oxidative stress: a unifying paradigm in hypertension. Canadian Journal of Cardiology, 36(5): 659-670.
  51. Gideon, A., Sauter, C., Fieres, J., Berger, T., Renner, B., & Wirtz, P. H. (2020).Kinetics and interrelations of the renin aldosterone response to acute psychosocial stress: a neglected stress system. The Journal of Clinical Endocrinology & Metabolism,105(3): e762-e773.
  52. Freeman, M. W., Bond, M., Murphy, B., Hui, J., & Isaacsohn, J. (2023). Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertension Research, 46(1): 108-118.
  53. Ferreira, N. S., Tostes, R. C., Paradis, P., & Schiffrin, E. L. (2021). Aldosterone, inflammation, immune system, and hypertension. American Journal of Hypertension,34(1): 15-27.
Statistics
Article View: 44
PDF Download: 32