Comparative Effects of Platelet-Rich Plasma and Erythropoietin on Oxidant/Antioxidant Balance in Diabetic Rats

Document Type : Original Articles

Authors

1 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Iran.

3 Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

4 Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahvaz, Iran

10.32592/ARI.2025.80.2.603

Abstract

Diabetes is a persistent metabolic disease represented by hyperglycemia that leads to oxidative stress caused by oxidant/antioxidant imbalance. Platelet-Rich Plasma (PRP) has been utilized clinically to stimulate tissue repair and cell proliferation in various medical fields. Erythropoietin (EPO) has shown protective effects in various tissues, mitigating ischemia-reperfusion injury and promoting tissue regeneration. This study aimed to assess the effects of PRP and EPO on the oxidant/antioxidant balance in diabetic rats. A total of 30 male rats were assigned into five groups: 1. Control; 2. Diabetic control, diabetes induced using streptozotocin (STZ); 3. Diabetic + PRP: PRP was administered subcutaneously at 0.5 ml/kg two times a week for four weeks in diabetic rats; 4. Diabetic + EPO: EPO was administered at 300 units/kg three times a week for four weeks in diabetic rats; and 5. Diabetic + PRP + EPO: a combination of both PRP and EPO was administered for four weeks. Diabetic rats showed significant reductions in superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathion (GSH) levels and a rise in malondialdehyde (MDA) concentration in contrast to controls (p<0.05). PRP and EPO treatments significantly increased SOD, GPX, and GSH quantities (p<0.05) and lowered MDA concentrations compared to untreated diabetic rats. The combination therapy group exhibited the highest improvements in antioxidant activities. This study demonstrates that both PRP and EPO exhibit significant antioxidant effects in diabetic rats, with the combined treatment showing the most pronounced improvements in oxidative stress markers. These results provide a foundation for potential clinical applications of PRP and EPO in enhancing antioxidant defenses and reducing oxidative damage in diabetic patients.

Keywords

Main Subjects


  1. Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna journal of medicine. 2020;10(04):174-88.
  2. Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. Type 1 diabetes mellitus. Nature reviews Disease primers. 2017;3(1):1-17.
  3. DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nature reviews Disease primers. 2015;1(1):1-22.
  4. Gregg EW, Sattar N, Ali MK. The changing face of diabetes complications. The lancet Diabetes & endocrinology. 2016;4(6):537-47.
  5. Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nature reviews nephrology. 2020;16(7):377-90.
  6. Moghtadaei Khorasgani E, Khani A. Investigating the effect of hydroalcoholic extract of eryngos on plasma concentration of blood glucose, blood cells and pancreatic tissue in diabetic rats. Iranian Journal of Veterinary Medicine. 2021;15(4):440-51.
  7. Shahsavari M, Norouzi P, Kalalianmoghaddam H, Teimouri M. Effects of kudzu root on oxidative stress and inflammation in streptozotocin-induced diabetic rats. Iranian Journal of Veterinary Medicine. 2023;17(4):401-8.
  8. Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress—A concise review. Saudi pharmaceutical journal. 2016;24(5):547-53.
  9. Yaribeygi H, Sathyapalan T, Atkin SL, Sahebkar A. Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxidative medicine and cellular longevity. 2020;2020(1):8609213.
  10. Qian Y, Han Q, Chen W, Song J, Zhao X, Ouyang Y, et al. Platelet-rich plasma derived growth factors contribute to stem cell differentiation in musculoskeletal regeneration. Frontiers in chemistry. 2017;5:89.
  11. Marques LF, Stessuk T, Camargo ICC, Sabeh Junior N, Santos LD, Ribeiro-Paes JT. Platelet-rich plasma (PRP): methodological aspects and clinical applications. Platelets. 2015;26(2):101-13.
  12. Elmongy NF, Meawad SB, Elshora SZ, Atwa AH, Hammad AM, Mehanna OM, et al. Platelet‐rich plasma ameliorates neurotoxicity induced by silver nanoparticles in male rats via modulation of apoptosis, inflammation, and oxidative stress. Journal of Biochemical and Molecular Toxicology. 2023;37(9):e23420.
  13. Cernaro V, Coppolino G, Visconti L, Rivoli L, Lacquaniti A, Santoro D, et al. Erythropoiesis and chronic kidney disease–related anemia: From physiology to new therapeutic advancements. Medicinal research reviews. 2019;39(2):427-60.
  14. Galli L, Ricci C, Egan CG. Epoetin beta for the treatment of chemotherapy-induced anemia: an update. OncoTargets and therapy. 2015:583-91.
  15. Peng B, Kong G, Yang C, Ming Y. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell death & disease. 2020;11(2):79.
  16. Niu H-S, Chang C-H, Niu C-S, Cheng J-T, Lee K-S. Erythropoietin ameliorates hyperglycemia in type 1-like diabetic rats. Drug design, development and therapy. 2016:1877-84.
  17. Maiese K. Erythropoietin and diabetes mellitus. World journal of diabetes. 2015;6(14):1259.
  18. Zhang P, Li D, Yang Z, Xue P, Liu X. Nrf2/HO-1 pathway is involved the anti-inflammatory action of intrauterine infusion of platelet-rich plasma against lipopolysaccharides in endometritis. Immunopharmacology and Immunotoxicology. 2022;44(1):119-28.
  19. Osikov M, Telesheva L, Ageev YI. Antioxidant effect of erythropoietin during experimental chronic renal failure. Bulletin of Experimental Biology and Medicine. 2015;160:202-4.
  20. Wang-Fischer Y, Garyantes T. Improving the reliability and utility of streptozotocin‐induced rat diabetic model. Journal of diabetes research. 2018;2018(1):8054073.
  21. Zarin M, Karbalaei N, Keshtgar S, Nemati M. Platelet-rich plasma improves impaired glucose hemostasis, disrupted insulin secretion, and pancreatic oxidative stress in streptozotocin-induced diabetic rat. Growth Factors. 2019;37(5-6):226-37.
  22. Behmanesh MA, Efani Majd N, Shahriari A, Nnajafzadeh H. Evaluation of antioxidant potential of Aloe vera and pituitary sexual hormones after experimental diabetes in male rats. Iran J Vet Med. 2017;11(2):164-74.
  23. Caturano A, D’Angelo M, Mormone A, Russo V, Mollica MP, Salvatore T, et al. Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Current Issues in Molecular Biology. 2023;45(8):6651-66.
  24. Eguchi N, Vaziri ND, Dafoe DC, Ichii H. The role of oxidative stress in pancreatic β cell dysfunction in diabetes. International journal of molecular sciences. 2021;22(4):1509.
  25. Darenskaya M, Kolesnikova La, Kolesnikov S. Oxidative stress: pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. Bulletin of experimental biology and medicine. 2021;171(2):179-89.
  26. Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y. Oxidative stress and diabetes: antioxidative strategies. Frontiers of medicine. 2020;14:583-600.
  27. Elksnis A, Martinell M, Eriksson O, Espes D. Heterogeneity of metabolic defects in type 2 diabetes and its relation to reactive oxygen species and alterations in beta-cell mass. Frontiers in physiology. 2019;10:107.
  28. Sánchez M, Anitua E, Delgado D, Sanchez P, Prado R, Orive G, et al. Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration. Expert opinion on biological therapy. 2017;17(2):197-212.
  29. El‐Sharkawy H, Kantarci A, Deady J, Hasturk H, Liu H, Alshahat M, et al. Platelet‐rich plasma: growth factors and pro‐and anti‐inflammatory properties. Journal of periodontology. 2007;78(4):661-9.
  30. Bader R, Ibrahim JN, Moussa M, Mourad A, Azoury J, Azoury J, et al. In vitro effect of autologous platelet‐rich plasma on H2O2‐induced oxidative stress in human spermatozoa. Andrology. 2020;8(1):191-200.
  31. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxidants & redox signaling. 2014;20(7):1126-67.
  32. Tognoloni A, Bartolini D, Pepe M, Di Meo A, Porcellato I, Guidoni K, et al. Platelets rich plasma increases antioxidant defenses of tenocytes via Nrf2 signal pathway. International Journal of Molecular Sciences. 2023;24(17):13299.
  33. Zhang Y-y, Yao M, Zhu K, Xue R-r, Xu J-h, Cui X-j, et al. Neurological recovery and antioxidant effect of erythropoietin for spinal cord injury: A systematic review and meta-analysis. Frontiers in Neurology. 2022;13:925696.
  34. Martins RP, Hartmann DD, de Moraes JP, Soares FAA, Puntel GO. Platelet-rich plasma reduces the oxidative damage determined by a skeletal muscle contusion in rats. Platelets. 2016;27(8):784-90.
  35. Bailey DM, Lundby C, Berg RMG, Taudorf S, Rahmouni H, Gutowski M, et al. On the antioxidant properties of erythropoietin and its association with the oxidative–nitrosative stress response to hypoxia in humans. Acta Physiologica. 2014;212(2):175-87.
  36. Katavetin P, Tungsanga K, Eiam-Ong S, Nangaku M. Antioxidative effects of erythropoietin. Kidney International. 2007;72:S10-S5.
  37. Maltaneri RE, Chamorro ME, Nesse AB, Vittori DC. Neuroprotection induced by erythropoietin. Natural Molecules in Neuroprotection and Neurotoxicity. 2024:527-47.
  38. Tanaka T, Nangaku M. Recent advances and clinical application of erythropoietin and erythropoiesis-stimulating agents. Experimental cell research. 2012;318(9):1068-73.
  39. Rani AJ, Mythili S. Study on total antioxidant status in relation to oxidative stress in type 2 diabetes mellitus. Journal of clinical and diagnostic research: JCDR. 2014;8(3):108.