Fruktoz ile İndüklenmiş Deneysel Metabolik Sendrom Modelinde Kuersetinin Oksidatif Stres Parametrelerine Etkisi
Abstract
Amaç: Metabolik Sendromun (MetS) artan yaygınlığı ile birlikte, oksidatif stresi yönetmek için antioksidan tedavilere olan ilgi artmaktadır. Fruktoz, önemli bir metabolik stresör ve işlenmiş gıdalarda yaygın olarak kullanılan bir tatlandırıcı olarak bu durumda önemli bir rol oynamaktadır. Bu çalışma, quercetinin MetS bileşenleri üzerindeki etkilerini, özellikle fruktoz ile indüklenen MetS modelinde karaciğer dokusundaki oksidatif stresi hafifletme yeteneğini değerlendirmektedir.
Gereç ve Yöntemler: 24 tane Sprague-Dawley sıçanı rastgele dört gruba ayrıldı: kontrol, fruktoz, kuersetin ve fruktoz+kuersetin. Quercetin (15 mg/kg/gün) oral gavaj yoluyla uygulanırken, %20 fruktoz çözeltisi 10 hafta boyunca içme suyu ile verildi. MetS’in doğrulanması için vücut ağırlığı, kan basıncı, serum glukoz, trigliserid, insülin seviyeleri ve insülin direnci gibi temel metabolik parametreler değerlendirildi. Karaciğer dokusu malondialdehit (MDA), ileri oksidasyon protein ürünleri (AOPP), nitrik oksit (NO), toplam antioksidan kapasite (TAS), toplam oksidan kapasite (TOS) ve oksidatif stres indeksi (OSI) gibi oksidatif stres belirteçleri açısından analiz edildi.
Bulgular: Fruktoz uygulaması, obezite, hipertansiyon, hipertrigliseridemi, hiperglisemi ve insülin direnci gibi temel metabolik sendrom bileşenlerini başarıyla indükledi. Kuersetin, fruktoz kaynaklı hipertansiyon ve insülin direncini önemli ölçüde azalttı, ancak obezite, hiperglisemi ve hipertrigliseridemi üzerindeki etkileri sınırlıydı. Fruktoz uygulaması, karaciğer MDA, AOPP ve TOS seviyelerini belirgin şekilde artırırken, NO ve TAS seviyelerindeki artış istatistiksel olarak anlamlı değildi. Fruktoz ile birlikte kuersetin uygulanması, kontrol grubuna kıyasla anlamlı derecede yüksek MDA seviyelerine yol açarken, AOPP seviyelerinde belirgin bir azalma gözlendi.
Sonuç: Uygulanan dozda kuersetin, fruktozun yol açtığı lipid peroksidasyonunu hafifletmede sınırlı bir etki gösterdi; ancak protein oksidasyonu ve NO seviyelerini modüle ederek dikkate değer bir antioksidan aktivite gözlendi. Bu bulgular, metabolik sendrom patogenezi hakkında değerli bilgiler sunmakta ve temel bileşenlerine yönelik potansiyel terapötik yaklaşımlara işaret etmektedir.
References
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- Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007; 137(11): 2405-11.https://doi.org/10.1093/jn/137.11.2405
- Papakyriakopoulou P, Velidakis N, Khattab E, Valsami G, Korakianitis I, Kadoglou NPE. Potential Pharmaceutical applications of quercetin in cardiovascular diseases. Pharmaceuticals. 2022; 15(8): 1-23. https://doi.org/10.3390/ph15081019
- Lubawy M. High-fructose diet – ınduced hyperuricemia accompanying metabolic syndrome – mechanisms and dietary therapy proposals. nt. J. Environ. Res. Public Health. 2023; 20(4): 3596. https://doi.org/10.3390/ijerph20043596
- Soleimani M, Barone S, Luo H, Zahedi K. Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt. Int J Mol Sci. 2023; 24(5): 4294. https://doi.org/10.3390/ijms24054294
- Hosseini A, Razavi BM, Banach M, Hosseinzadeh H. Quercetin and metabolic syndrome: A review. Phyther Res. 2021; 35(10): 5352-64. https://doi.org/10.1002/ptr.7144.
- Qi W, Qi W, Xiong D, Long M. Quercetin: Its antioxidant mechanism, antibacterial properties and potential application in prevention and control of toxipathy. Molecules. 2022; 27(19): 6545. https://doi.org/10.3390/molecules27196545.
- Vashishth K, Singh SK, Jain A, Bhatia A, Sharma YP. Pathological involvement of apoptotic and inflammatory molecules in cardiovascular remodeling in rats on high fructose diet-induced metabolic syndrome. J Food Biochem. 2022; 46(7): 14107. https://doi.org/10.1111/jfbc.14107
- Kitagawa A, Ohta Y, Ohashi K, Yashiro K, Fukuzawa K. Effect of high fructose-induced metabolic syndrome on tissue vitamin e and lipid peroxide levels in rats. J Nutr Sci Vitaminol (Tokyo). 2020; 66(2): 200-6. https://doi.org/10.3177/jnsv.66.200.
- Wang Y, Thatcher SE, Cassis LA. Measuring Blood Pressure Using a Noninvasive Tail Cuff Method in Mice. Methods Mol Biol. 2017; 1614: 69-73. https://doi.org/10.1007/978-1-4939-7030-8_6.
- Bernardis LL, Patterson BD. Correlation between “Lee index” and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol. 1968; 40(4): 527–8. https://doi.org/10.1677/joe.0.0400527.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1): 265-75. http://dx.doi.org/10.1016/S0021-9258(19)52451-6
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2): 351-8. https://doi.org/10.1016/0003-2697(79)90738-3.
- Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996; 49(5): 1304-13. https://doi.org/10.1038/ki.1996.186.
- Sánchez-Rodríguez MA, Mendoza-Núñez VM. Oxidative stress indexes for diagnosis of health or disease in humans. Oxid Med Cell Longev. 2019; 2019. https://doi.org/10.1155/2019/4128152.
- Alizadeh, Seyedeh Roya Ebrahimzadeh MA. Quercetin derivatives: Drug design, development, and biological activities, a review. Eur J Med Chem. 2022; 5: 229. https://doi.org/10.1016/j.ejmech.2021.114068.
- Suganya N, Dornadula S, Chatterjee S, Mohanram RK. Quercetin improves endothelial function in diabetic rats through inhibition of endoplasmic reticulum stress-mediated oxidative stress. Eur J Pharmacol. 2018; 819: 80-8. https://doi.org/10.1016/j.ejphar.2017.11.034
- Zhou W, Wang F, Qian X, Luo S, Wang Z, Gao X, et al. Quercetin protects endothelial function from inflammation induced by localized disturbed flow by inhibiting NRP2 -VEGFC complex. Int Immunopharmacol. 2023; 116: 109842. https://doi.org/10.1016/j.intimp.2023.109842
- El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation. Front Med. 2022; 9: 1-15. https://doi.org/10.3389/fmed.2022.904756.
- Toop CR, Gentili S. Fructose beverage consumption induces a metabolic syndrome phenotype in the rat: A systematic review and meta-analysis. Nutrients. 2016; 8(9): 577. https://doi.org/10.3390/nu8090577
- Ibrahim KG, Chivandi E, Mojiminiyi FBO, Erlwanger KH. The response of male and female rats to a high-fructose diet during adolescence following early administration of Hibiscus sabdariffa aqueous calyx extracts. J Dev Orig Health Dis. 2017; 8(6): 628-637. https://doi.org/10.1017/S204017441700040X
- Sari DR, Ramadhan RN, Agustin D, Munir M, Izzatunnisa N, Susanto J, et al. The effect of exercise ıntensity on anthropometric parameters and renal damage in high fructose-ınduced mice. Retos. 2024; 51: 1194-209. https://doi.org/10.47197/retos.v51.101189
- dos Santos F, Moraes-Silva IC, Moreira ED, Irigoyen MC. The role of the baroreflex and parasympathetic nervous system in fructose-induced cardiac and metabolic alterations. Sci Rep. 2018; 8(1): 1-9. http://dx.doi.org/10.1038/s41598-018-29336-3
- Mamikutty N, Thent ZC, Sapri SR, Sahruddin NN, Mohd Yusof MR, Haji Suhaimi F. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. Biomed Res Int. 2014; 2014. https://doi.org/10.1155/2014/263897
- Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019; 24(6): 1123. https://doi.org/10.3390/molecules24061123
- Yang D, Wang T, Long M, Li P. Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine. Oxid Med Cell Longev. 2020; 2020. https://doi.org/10.1155/2020/8825387
- Kocaman Kalkan K, Şen S, Narlı B, Seymen CM, Yılmaz C. Effects of quercetin on hepatic fibroblast growth factor-21 (FGF-21) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) levels in rats fed with high fructose. Mol Biol Rep. 2023; 50(6): 4983-97. https://doi.org/10.1007/s11033-023-08444-y
- Er F. Fruktoz aracılıklı metabolik sendrom modelinde kuersetin uygulaması ve egzersizin etkisi. Gazi University; 2017.
- Roslan J, Giribabu N, Karim K, Salleh N. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats. Biomed Pharmacother. 2017; 86: 570-82. http://dx.doi.org/10.1016/j.biopha.2016.12.044
- Zhao X, Wang J, Deng Y, Liao L, Zhou M, Peng C, et al. Quercetin as a protective agent for liver diseases: A comprehensive descriptive review of the molecular mechanism. Phyther Res. 2021; 35(9): 4727-47. https://doi.org/10.1002/ptr.7104
- Gorbenko NI, Borikov OY, Kiprych T V, Ivanova O V, Taran K V, Litvinova TS. Quercetin improves myocardial redox status in rats with type 2 diabetes. Endocr Regul. 2021; 55(3): 142-52. https://doi.org/ 10.2478/enr-2021-0015.
- Abo-youssef AM. Protective effect of rosiglitazone, quercetin, and their combination on fructose-induced metabolic syndrome in rats. Indian J Pharmacol. 2015; 47(6): 620-6. https://doi.org/10.4103/0253-7613.169577
- Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol Part C Toxicol Pharmacol. 2003; 135(3): 357-64. https://doi.org/10.1016/s1532-0456(03)00140-6
- Susanti N, Mustika A, Khotib J. Clinacanthus nutans leaf extract reduces pancreatic β-cell apoptosis by inhibiting JNK activation and modulating oxidative stress and inflammation in streptozotocin-induced diabetic rats. Open Vet J. 2024; 14(2): 730-7. https://doi.org/10.5455/OVJ.2024.v14.i2.13
- Tsai CF, Chen GW, Chen YC, Shen CK, Lu DY, Yang LY, et al. Regulatory effects of quercetin on M1/M2 macrophage polarization and oxidative/antioxidative balance. Nutrients. 2022; 14(1): 1-21. https://doi.org/10.3390/nu14010067
The Effect of Quercetin on Oxidative Stress Parameters in A Fructose-Induced Experimental Metabolic Syndrome Model
Abstract
Aim: With the rising prevalence of Metabolic Syndrome (MetS), antioxidant therapies for managing oxidative stress are gaining attention. Fructose, a major metabolic stressor and a prevalent sweetener in processed foods, plays a significant role in this condition. This study evaluates quercetin's effects on MetS components, specifically its ability to alleviate oxidative stress in liver tissue within a fructose-induced MetS model.
Material and Methods: 24 Sprague-Dawley rats were randomly divided into four groups: control, fructose, quercetin, and fructose+quercetin. Quercetin (15 mg/kg/day) was administered via gavage, and a 20% fructose solution was provided in drinking water over 10 weeks. Key metabolic parameters, including body weight, blood pressure, serum glucose, triglycerides, insulin levels, and insulin resistance, were assessed to confirm MetS. Liver tissue was analyzed for oxidative stress markers, including malondialdehyde (MDA), advanced oxidation protein products (AOPP), nitric oxide (NO), total antioxidant status (TAS), total oxidant status (TOS), and the oxidative stress index (OSI).
Results: Fructose administration successfully induced key metabolic syndrome components, such as obesity, hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Quercetin significantly reduced fructose-induced hypertension and insulin resistance, though its effects on obesity, hyperglycemia, and hypertriglyceridemia were limited. Fructose exposure markedly elevated liver MDA, AOPP, and TOS levels, with nonsignificant increases in NO and TAS. Co-administration of quercetin with fructose resulted in significantly higher MDA levels compared to controls, while AOPP levels were notably reduced.
Conclusion: At the administered dose, quercetin showed limited efficacy in mitigating fructose-induced lipid peroxidation; however, it displayed notable antioxidant activity by modulating protein oxidation and NO levels. These findings provide valuable insights into the pathogenesis of metabolic syndrome and suggest potential therapeutic avenues for targeting its underlying components.
Ethical Statement
This study was conducted in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals and was approved by the Gazi University Ethics Committee, G.Ü.ET-17.088, 2017. All procedures were designed to minimize animal suffering and were performed by trained personnel in accordance with ethical guidelines.
Supporting Institution
Gazi University
References
- 1Dupas J, Feray A, Goanvec C, Guernec A, Samson N, Bougaran P, et al. Metabolic syndrome and hypertension resulting from fructose enriched diet in wistar rats. Biomed Res Int. 2017; 2017. https://doi.org/10.1155/2017/2494067
- Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007; 137(11): 2405-11.https://doi.org/10.1093/jn/137.11.2405
- Papakyriakopoulou P, Velidakis N, Khattab E, Valsami G, Korakianitis I, Kadoglou NPE. Potential Pharmaceutical applications of quercetin in cardiovascular diseases. Pharmaceuticals. 2022; 15(8): 1-23. https://doi.org/10.3390/ph15081019
- Lubawy M. High-fructose diet – ınduced hyperuricemia accompanying metabolic syndrome – mechanisms and dietary therapy proposals. nt. J. Environ. Res. Public Health. 2023; 20(4): 3596. https://doi.org/10.3390/ijerph20043596
- Soleimani M, Barone S, Luo H, Zahedi K. Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt. Int J Mol Sci. 2023; 24(5): 4294. https://doi.org/10.3390/ijms24054294
- Hosseini A, Razavi BM, Banach M, Hosseinzadeh H. Quercetin and metabolic syndrome: A review. Phyther Res. 2021; 35(10): 5352-64. https://doi.org/10.1002/ptr.7144.
- Qi W, Qi W, Xiong D, Long M. Quercetin: Its antioxidant mechanism, antibacterial properties and potential application in prevention and control of toxipathy. Molecules. 2022; 27(19): 6545. https://doi.org/10.3390/molecules27196545.
- Vashishth K, Singh SK, Jain A, Bhatia A, Sharma YP. Pathological involvement of apoptotic and inflammatory molecules in cardiovascular remodeling in rats on high fructose diet-induced metabolic syndrome. J Food Biochem. 2022; 46(7): 14107. https://doi.org/10.1111/jfbc.14107
- Kitagawa A, Ohta Y, Ohashi K, Yashiro K, Fukuzawa K. Effect of high fructose-induced metabolic syndrome on tissue vitamin e and lipid peroxide levels in rats. J Nutr Sci Vitaminol (Tokyo). 2020; 66(2): 200-6. https://doi.org/10.3177/jnsv.66.200.
- Wang Y, Thatcher SE, Cassis LA. Measuring Blood Pressure Using a Noninvasive Tail Cuff Method in Mice. Methods Mol Biol. 2017; 1614: 69-73. https://doi.org/10.1007/978-1-4939-7030-8_6.
- Bernardis LL, Patterson BD. Correlation between “Lee index” and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol. 1968; 40(4): 527–8. https://doi.org/10.1677/joe.0.0400527.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1): 265-75. http://dx.doi.org/10.1016/S0021-9258(19)52451-6
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2): 351-8. https://doi.org/10.1016/0003-2697(79)90738-3.
- Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996; 49(5): 1304-13. https://doi.org/10.1038/ki.1996.186.
- Sánchez-Rodríguez MA, Mendoza-Núñez VM. Oxidative stress indexes for diagnosis of health or disease in humans. Oxid Med Cell Longev. 2019; 2019. https://doi.org/10.1155/2019/4128152.
- Alizadeh, Seyedeh Roya Ebrahimzadeh MA. Quercetin derivatives: Drug design, development, and biological activities, a review. Eur J Med Chem. 2022; 5: 229. https://doi.org/10.1016/j.ejmech.2021.114068.
- Suganya N, Dornadula S, Chatterjee S, Mohanram RK. Quercetin improves endothelial function in diabetic rats through inhibition of endoplasmic reticulum stress-mediated oxidative stress. Eur J Pharmacol. 2018; 819: 80-8. https://doi.org/10.1016/j.ejphar.2017.11.034
- Zhou W, Wang F, Qian X, Luo S, Wang Z, Gao X, et al. Quercetin protects endothelial function from inflammation induced by localized disturbed flow by inhibiting NRP2 -VEGFC complex. Int Immunopharmacol. 2023; 116: 109842. https://doi.org/10.1016/j.intimp.2023.109842
- El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation. Front Med. 2022; 9: 1-15. https://doi.org/10.3389/fmed.2022.904756.
- Toop CR, Gentili S. Fructose beverage consumption induces a metabolic syndrome phenotype in the rat: A systematic review and meta-analysis. Nutrients. 2016; 8(9): 577. https://doi.org/10.3390/nu8090577
- Ibrahim KG, Chivandi E, Mojiminiyi FBO, Erlwanger KH. The response of male and female rats to a high-fructose diet during adolescence following early administration of Hibiscus sabdariffa aqueous calyx extracts. J Dev Orig Health Dis. 2017; 8(6): 628-637. https://doi.org/10.1017/S204017441700040X
- Sari DR, Ramadhan RN, Agustin D, Munir M, Izzatunnisa N, Susanto J, et al. The effect of exercise ıntensity on anthropometric parameters and renal damage in high fructose-ınduced mice. Retos. 2024; 51: 1194-209. https://doi.org/10.47197/retos.v51.101189
- dos Santos F, Moraes-Silva IC, Moreira ED, Irigoyen MC. The role of the baroreflex and parasympathetic nervous system in fructose-induced cardiac and metabolic alterations. Sci Rep. 2018; 8(1): 1-9. http://dx.doi.org/10.1038/s41598-018-29336-3
- Mamikutty N, Thent ZC, Sapri SR, Sahruddin NN, Mohd Yusof MR, Haji Suhaimi F. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. Biomed Res Int. 2014; 2014. https://doi.org/10.1155/2014/263897
- Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019; 24(6): 1123. https://doi.org/10.3390/molecules24061123
- Yang D, Wang T, Long M, Li P. Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine. Oxid Med Cell Longev. 2020; 2020. https://doi.org/10.1155/2020/8825387
- Kocaman Kalkan K, Şen S, Narlı B, Seymen CM, Yılmaz C. Effects of quercetin on hepatic fibroblast growth factor-21 (FGF-21) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) levels in rats fed with high fructose. Mol Biol Rep. 2023; 50(6): 4983-97. https://doi.org/10.1007/s11033-023-08444-y
- Er F. Fruktoz aracılıklı metabolik sendrom modelinde kuersetin uygulaması ve egzersizin etkisi. Gazi University; 2017.
- Roslan J, Giribabu N, Karim K, Salleh N. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats. Biomed Pharmacother. 2017; 86: 570-82. http://dx.doi.org/10.1016/j.biopha.2016.12.044
- Zhao X, Wang J, Deng Y, Liao L, Zhou M, Peng C, et al. Quercetin as a protective agent for liver diseases: A comprehensive descriptive review of the molecular mechanism. Phyther Res. 2021; 35(9): 4727-47. https://doi.org/10.1002/ptr.7104
- Gorbenko NI, Borikov OY, Kiprych T V, Ivanova O V, Taran K V, Litvinova TS. Quercetin improves myocardial redox status in rats with type 2 diabetes. Endocr Regul. 2021; 55(3): 142-52. https://doi.org/ 10.2478/enr-2021-0015.
- Abo-youssef AM. Protective effect of rosiglitazone, quercetin, and their combination on fructose-induced metabolic syndrome in rats. Indian J Pharmacol. 2015; 47(6): 620-6. https://doi.org/10.4103/0253-7613.169577
- Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol Part C Toxicol Pharmacol. 2003; 135(3): 357-64. https://doi.org/10.1016/s1532-0456(03)00140-6
- Susanti N, Mustika A, Khotib J. Clinacanthus nutans leaf extract reduces pancreatic β-cell apoptosis by inhibiting JNK activation and modulating oxidative stress and inflammation in streptozotocin-induced diabetic rats. Open Vet J. 2024; 14(2): 730-7. https://doi.org/10.5455/OVJ.2024.v14.i2.13
- Tsai CF, Chen GW, Chen YC, Shen CK, Lu DY, Yang LY, et al. Regulatory effects of quercetin on M1/M2 macrophage polarization and oxidative/antioxidative balance. Nutrients. 2022; 14(1): 1-21. https://doi.org/10.3390/nu14010067
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Biochemistry and Metabolomics (Other) |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | May 22, 2025 |
| Submission Date | November 6, 2024 |
| Acceptance Date | January 7, 2025 |
| Published in Issue | Year 2025 Volume: 15 Issue: 2 |
