The Effects of Itaconic Acid on Blood Coagulation and Hematological Parameters in Rats

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Basic Sciences, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 MSc Student, Department of Basic Sciences, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Associated Professor, Department of Basic Sciences, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background: Itaconic acid has anti-inflammatory, antioxidant, and immune system-modulating effects. This study aimed to investigate the effect of itaconic acid on blood coagulation and blood parameters in rats.
Methods: In this experiment, a total of 30 rats were examined. The control group consisted of healthy rats, for whom no intervention was performed, and they only received daily intraperitoneal injections of sunflower oil for 7 days. The aspirin group received a daily intraperitoneal injection of 26 mg/ml aspirin for 7 days. The itaconic acid group received daily intraperitoneal injections of itaconic acid with doses of 5, 10, and 20 mg per kilogram of body weight for 7 days. Coagulation tests such as CT, BT, PT, and aPTT, as well as hematological factors, were investigated.
Findings: Rats were given 5, 10, or 20 mg per kg of itaconic acid per body weight. As a result, there was an increase in the mean BT time compared to healthy rats (P < 0.05). No significant effects were observed on other investigated factors.
Conclusion: Itaconic acid did not cause significant changes in blood parameters, including platelet count, but significantly prolonged BT time in rats. It also had no significant effect on CT, PT, and aPTT.

Highlights

Kaveh Rahimi: PubMed, Google Scholar

Sharareh Bakhtazad: PubMed, Google Scholar

Mohammad Abbaszadeh: Google Scholar

Zohreh Ghotbeddin: PubMed, Google Scholar

Keywords

Main Subjects

References

  1. Ayodele OO, Onajobi FD, Osoniyi OR. Modulation of Blood Coagulation and Hematological Parameters by Crassocephalum crepidioides Leaf Methanol Extract and Fractions in STZ-Induced Diabetes in the Rat. TheScientificWorldJournal. 2020;2020:1036364.
  2. Tarandovskiy ID, Rajabi AA, Karnaukhova E, Buehler PW. Contradictory to its effects on thrombin, C1-inhibitor reduces plasmin generation in the presence of thrombomodulin. J Thromb Thrombolysis 2019; 48(1): 81-7.
  3. Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, et al. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 2016; 24(1): 158-66.
  4. Cordes T, Wallace M, Michelucci A, Divakaruni AS, Sapcariu SC, Sousa C, et al. Immunoresponsive gene 1 and itaconate inhibit succinate dehydrogenase to modulate intracellular succinate levels. J J Biol Chem 2016; 291(27): 14274-84.
  5. Li R, Zhang P, Wang Y, Tao K. Itaconate: a metabolite regulates inflammation response and oxidative stress. Oxid Med Cell Longev 2020; 2020: 5404780.
  6. Kuo PC, Weng WT, Scofield BA, Paraiso HC, Brown DA, Wang PY, et al. Dimethyl itaconate, an itaconate derivative, exhibits immunomodulatory effects on neuroinflammation in experimental autoimmune encephalomyelitis. J Neuroinflammation 2020; 17(1): 138.
  7. Zhang S, Jiao Y, Li C, Liang X, Jia H, Nie Z, et al. Dimethyl itaconate alleviates the inflammatory responses of macrophages in sepsis. Inflammation 2021; 44: 549-57.
  8. Marcero JR, Cox JE, Bergonia HA, Medlock AE, Phillips JD, Dailey HA. The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors. Blood Adv 2021; 5(23): 4831-41.
  9. Shvartsur R, Agam G, Uzzan S, Azab AN. Low-dose aspirin augments the anti-inflammatory effects of low-dose lithium in lipopolysaccharide-treated rats. Pharmaceutics 2022; 14(5): 54-62.
  10. Lin J, Ren J, Zhu B, Dai Y, Gao DS, Xia S, et al. Dimethyl itaconate attenuates CFA-Induced inflammatory pain via the NLRP3/ IL-1β signaling pathway. Front Pharmaco 2022; 13: 938979.
  11. Hirsh J, Street D, Cade JF, Amy H. Relation between bleeding time and platelet connective tissue reaction after Blood 1973; 41(3): 369-77.
  12. Larsen H. [72] Itaconic acid and related compounds. Methods in Enzymology. 3: Academic Press; 1957; 3: 437-44.
  13. Vidal I, Fernández-Florido E, Marrero AD, Castilla L, R. Quesada A, Martínez-Poveda B, et al. The immunomodulator dimethyl itaconate inhibits several key steps of angiogenesis in cultured endothelial cells. Int J Mol Sci 2022; 23(24): 15972.
  14. Teleky BE, Vodnar DC. Recent advances in biotechnological itaconic acid production, and application for a sustainable approach. Polymers (Basel) 2021; 13(20): 3574.
  15. Servatyari K, Ahmadi A, Kashefi H, Manbari MN, Rostami A, Moulodi MR. The effect of hydroalcoholic extract of Medicago sativa on liver function tests, blood biochemical factors and coagulation system in male rats [in Persian]. Sci J Kurdistan Univ Med Sci 2017; 21(6): 16-26.
  16. Chen H, Jin M, Wang YF, Wang YQ, Meng L, Li R, et al. Effect of Toona microcarpa Harms leaf extract on the coagulation system. Biomed Res Int 2014; 2014: 615363.
  17. Sander Y, Ariesanti Y, Roeslan MO, editors. Effect of Moringa oleifera Leaves on Human Blood Coagulation Process. [14-16 July 2021] 2021 IEEE International Conference on Health, Instrumentation & Measurement, and Natural Sciences (InHeNce).
Journal of Isfahan Medical School
Volume 43, Issue 804
4th Week, April
March and April 2025
Pages 95-101

Files

History

  • Receive Date: 21 April 2024
  • Accept Date: 26 January 2025

Share

How to cite

Statistics