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Hwaiz, Rundk, Jawdat, helen, Salim, Tavga, Merza, Mohammed, Al-Rawi, Rafil. (1404). RAS-Related C3 Botulinum Toxin Substrate 1 Inhibition Attenuates Platelet Chemokine Activation in Diabetes Mellitus. سامانه مدیریت نشریات علمی, 80(3), 733-742. doi: 10.32592/ARI.2025.80.3.733
Rundk Hwaiz; helen Jawdat; Tavga Salim; Mohammed Yousif Merza; Rafil Al-Rawi. "RAS-Related C3 Botulinum Toxin Substrate 1 Inhibition Attenuates Platelet Chemokine Activation in Diabetes Mellitus". سامانه مدیریت نشریات علمی, 80, 3, 1404, 733-742. doi: 10.32592/ARI.2025.80.3.733
Hwaiz, Rundk, Jawdat, helen, Salim, Tavga, Merza, Mohammed, Al-Rawi, Rafil. (1404). 'RAS-Related C3 Botulinum Toxin Substrate 1 Inhibition Attenuates Platelet Chemokine Activation in Diabetes Mellitus', سامانه مدیریت نشریات علمی, 80(3), pp. 733-742. doi: 10.32592/ARI.2025.80.3.733
Hwaiz, Rundk, Jawdat, helen, Salim, Tavga, Merza, Mohammed, Al-Rawi, Rafil. RAS-Related C3 Botulinum Toxin Substrate 1 Inhibition Attenuates Platelet Chemokine Activation in Diabetes Mellitus. سامانه مدیریت نشریات علمی, 1404; 80(3): 733-742. doi: 10.32592/ARI.2025.80.3.733

RAS-Related C3 Botulinum Toxin Substrate 1 Inhibition Attenuates Platelet Chemokine Activation in Diabetes Mellitus

Archives of Razi Institute
مقاله 23، دوره 80، شماره 3، مرداد و شهریور 2025، صفحه 733-742    اصل مقاله (552.29 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.3.733
نویسندگان
Rundk Hwaiz1؛ helen Jawdat2؛ Tavga Salim3؛ Mohammed Yousif Merza* 4؛ Rafil Al-Rawi5
1Department of Nutrition and Dietetics, College of Health Sciences, Hawler Medical University, Kurdistan, Iraq.
2Department of Medical Biochemical Analysis, Cihan University-Erbil, Kurdistan Region, Iraq
3Department of Medical Microbiology, College of Health Sciences, Hawler Medical University, Kurdistan, Iraq.
4Department of Clinical Analysis College of Pharmacy Hawler Medical University, Erbil, Kurdistan 100M street Erbil, Iraq
5Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan, Iraq.
چکیده
Diabetes mellitus (DM) is a prevalent cause of platelet (PLT) activation. Inflammation-induced dysregulated PLT function adds to chronic problems. Ras-related C3 botulinum toxin substrate 1 (Rac1), a 21 kDa G-protein, has been shown to modulate many PLT activities; we hypothesized that Rac1 may influence the PLT release of CXCL4 and CCL5, contributing to macrovascular and microvascular problems in DM. The study included Swiss albino male mice pretreated with the Rac1 inhibitor NSC23766 and streptozotocin (STZ) to induce diabetes. A sample of 150 diabetic patients and 50 healthy controls was also analyzed. Statistical analyses were performed using Mann-Whitney tests One hundred fifty confirmed diabetic patients which they visit Layla Qasim health center for diabetes and 50 healthy individuals were included in this study. The serum CXCL4 and CCL5 in diabetic patients and healthy volunteer were measured. Swiss albino male mice were given a pretreatment of 5 mg/kg of the Rac1 inhibitor NSC23766 and then injected with streptozotocin at a dosage of 45 mg/kg body weight, twice daily for five days. Rac1 activity in the PLT was measured using pulldown assay and western blot method. Blood chemokine concentrations were also assessed using ELISA, and histological scores for the kidney, liver, pancreas, and lung were evaluated. CXCL4 and CCL5 levels were markedly elevated in DM patients relative to healthy persons. Our findings indicated that streptozotocin developed diabetes mellitus in mice. GTP-Rac1 was induced in diabetic mice and pretreatment with NSC23766 was significantly lower compared to vehicle group. Furthermore, compared to the sham group, diabetic mice had significantly greater levels of CXCL4 and CCL5 (P < 0.05). CXCL4 levels were reduced by 80% following Rac1 inhibition (P < 0.05), while CCL5 levels decreased by 55.5% (P < 0.05). The current research indicates that Rac1 plays a pivotal role in releasing PLT chemokines due to diabetes-induced inflammation in several organs, and inhibiting Rac1 may represent a novel therapeutic approach to managing inflammation in diabetic individuals.
کلیدواژه‌ها
Rac1؛ Platelet؛ CXCL4, CCL5؛ Diabetes Mellitus
مراجع
  1. Care D. Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl 1):S8-S16.
  2. Thipsawat S. Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature. Diabetes and Vascular Disease Research. 2021;18(6):14791641211058856.
  3. Khil J, Kim SM, Chang J, Choi S, Lee G, Son JS, et al. Changes in total cholesterol level and cardiovascular disease risk among type 2 diabetes patients. Scientific reports. 2023;13(1):8342.
  4. Santilli F, Vazzana N, Liani R, Guagnano MT, Davi G. Platelet activation in obesity and metabolic syndrome. Obesity reviews. 2012;13(1):27-42.
  5. Bakogiannis C, Sachse M, Stamatelopoulos K, Stellos K. Platelet-derived chemokines in inflammation and atherosclerosis. Cytokine. 2019;122:154157.
  6. Li J, Nie Z, Ge Z, Shi L, Gao B, Yang Y. Prevalence of dyslipidemia, treatment rate and its control among patients with type 2 diabetes mellitus in Northwest China: a cross-sectional study. Lipids in health and disease. 2022;21(1):77.
  7. Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020;69(9):1691-705.
  8. Zimmer S, Goody PR, Oelze M, Ghanem A, Mueller CF, Laufs U, et al. Inhibition of Rac1 GTPase decreases vascular oxidative stress, improves endothelial function, and attenuates atherosclerosis development in mice. Frontiers in Cardiovascular Medicine. 2021;8:680775.
  9. Furman BL. Streptozotocin‐induced diabetic models in mice and rats. Current protocols in pharmacology. 2015;70(1):5.47. 1-5.. 20.
  10. Hwaiz R, Hasan Z, Rahman M, Zhang S, Palani K, Syk I, et al. Rac1 signaling regulates sepsis-induced pathologic inflammation in the lung via attenuation of Mac-1 expression and CXC chemokine formation. journal of surgical research. 2013;183(2):798-807.
  11. Siddiqui SA, Or Rashid MM, Uddin MG, Robel FN, Hossain MS, Haque MA, et al. Biological efficacy of zinc oxide nanoparticles against diabetes: a preliminary study conducted in mice. Bioscience reports. 2020;40(4):BSR20193972.
  12. Ibrahim KE, Al-Mutary MG, Bakhiet AO, Khan HA. Histopathology of the liver, kidney, and spleen of mice exposed to gold nanoparticles. Molecules. 2018;23(8):1848.
  13. Lorenty K, Harding E, Fenton O. A Call to Action to Address the Burden of Cardiovascular Disease in People with Diabetes. Global heart. 2022;17(1):87.
  14. Henríquez-Olguin C, Knudsen JR, Raun SH, Li Z, Dalbram E, Treebak JT, et al. Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise. Nature communications. 2019;10(1):4623.
  15. Nikolaeva M, Johnstone M. Nitric oxide, its role in diabetes mellitus and methods to improve endothelial function. Diabetes and Cardiovascular Disease: Springer; 2023. p. 159-200.
  16. Chan KS, Shelat VG. The role of platelet-lymphocyte ratio in hepatocellular carcinoma: a valuable prognostic marker. Translational cancer research. 2022;11(12):4231.
  17. Davì G, Patrono C. Platelet activation and atherothrombosis. New England Journal of Medicine. 2007;357(24):2482-94.
  18. Forrester JV, Kuffova L, Delibegovic M. The role of inflammation in diabetic retinopathy. Frontiers in immunology. 2020;11:583687.
  19. Grommes J, Alard J-E, Drechsler M, Wantha S, Mörgelin M, Kuebler WM, et al. Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. American journal of respiratory and critical care medicine. 2012;185(6):628-36.
  20. Zarbock A, Polanowska-Grabowska RK, Ley K. Platelet-neutrophil-interactions: linking hemostasis and inflammation. Blood reviews. 2007;21(2):99-111.
  21. Targher G, Byrne CD. Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease. Nature Reviews Nephrology. 2017;13(5):297-310.
  22. Chiu TT, Patel N, Shaw AE, Bamburg JR, Klip A. Arp2/3-and cofilin-coordinated actin dynamics is required for insulin-mediated GLUT4 translocation to the surface of muscle cells. Molecular biology of the cell. 2010;21(20):3529-39.
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