The effect of diosgenin on mitochondrial health and neutrophil infiltration indices in methotrexate-induced liver damage in the rat

Document Type : Original Article

Authors

1 Department of Physiology, School of Medicine, Shahed University, Tehran, Iran

2 Neurophysiology Research Center, Shahed University, Tehran, Iran

3 Department of Biology, School of Basic Sciences, Shahed University, Tehran, Iran

Abstract

Background and Objective: The liver is the largest gland in the body with multiple functions. Methotrexate causes acute and chronic liver damage. In this study, the effects of diosgenin were investigated as a steroidal sapogenin on mitochondrial membrane potential (MMP) and neutrophil infiltration activity in a methotrexate-induced liver injury model in male rats.
Materials and Methods: 40 rats in 5 groups; control, control treated with diosgenin 50 mg/kg, methotrexate at a dose of 20 mg/kg (i.p) and two groups treated with diosgenin at doses 10, 50 mg/kg (gavage) were divided. The rats were anesthetized and the liver tissue was isolated after killing. After tissue homogeneity, neutrophil infiltration activity and mitochondrial membrane potential were measured. For statistical analysis, one-way ANOVA and Tukey post-test were used, and the significance level was p <0.05.
Results: The potential of the mitochondrial membrane in the methotrexate group treated with diosgenin 10 mg/kg was significantly reduced compared to the control group and in the group treated with diosgenin 50 mg/kg was significantly increased compared to methotrexate. On the other hand, myeloperoxidase increased significantly in the methotrexate group and treated with diosgenin 10 mg/kg compared to the control group and decreased significantly in the group treated with diosgenin 50 mg/kg compared to the methotrexate group.
Conclusion: Diosgenin at a dose of 50 mg/kg in the methotrexate-induced liver injury model was able to improve mitochondrial health and reduced neutrophil infiltration.

Keywords


  1. Williams PL. Gray's Anatomy: The Anatomical Basis of Clinical PracticeGray's Anatomy: The Anatomical Basis of Clinical Practice. 42th ed 2021 2021.
  2. Snell MD, S R. Clinical Anatomy for Medical Students. 5th ed: ‎ Little Brown & Co; 1995.
  3. L G. Textbook of Histology. 5th ed. Cannada: Deepthi Unni; 2021 20th November 2015; 443.
  4. Chao X, Wang H, Jaeschke H, Ding WX. Role and mechanisms of autophagy in acetaminophen‐induced liver injury. Liver International. 2018;38(8):1363-74.
  5. Luedde T, Kaplowitz N, Schwabe RF. Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology 2014;147(4):765-83. e4.
  6. Kargapolova Y, Geißen S, Zheng R, Baldus S, Winkels H, Adam M. The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication. Antioxidants 2021;10(4):562.
  7. Schafranski M, Merlini A, Araújo E, Camargo N, Arruda P. Methotrexate: Update on Pharmaclology. Clinical Applications and Warmings 2012.
  8. Uzar E, Koyuncuoglu HR, Uz E, Yilmaz HR, Kutluhan S, Kilbas S, et al. The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Molecular and Cellular Biochemistry 2006;291(1):63-8.
  9. Vardi N, Parlakpinar H, Ozturk F, Ates B, Gul M, Cetin A, et al. Potent protective effect of apricot and β-carotene on methotrexate-induced intestinal oxidative damage in rats. Food and Chemical Toxicology 2008;46(9):3015-22.
  10. Li S, Li H, Xu X, Saw PE, Zhang L. Nanocarrier-mediated antioxidant delivery for liver diseases. Theranostics 2020;10(3):1262.
  11. Jesus M, Martins AP, Gallardo E, Silvestre S. Diosgenin: recent highlights on pharmacology and analytical methodology. Journal of Analytical Methods in Chemistry 2016.
  12. Chen Y, Xu X, Zhang Y, Liu K, Huang F, Liu B, et al. Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK. The Journal of Steroid Biochemistry and Molecular Biology 2016;155:155-65.
  13. Khan H, Saeed M, Rauf A, Khan MA, Muhammad N. Antimicrobial and inhibition on heat-induced protein denaturation of constituents isolated from Polygonatum verticillatum rhizomes. Natural Product Research 2015;29(22):2160-3.
  14. Mohamadi-Zarch S-M, Baluchnejadmojarad T, Nourabadi D, Khanizadeh AM, Roghani M. Protective effect of diosgenin on LPS/D-Gal-induced acute liver failure in C57BL/6 mice. Microbial Pathogenesis 2020;146:104243.
  15. Daggulli M, Dede O, Utangac MM, Bodakci MN, Hatipoglu NK, Penbegul N, et al. Protective effects of carvacrol against methotrexate-induced testicular toxicity in rats. International Journal of Clinical and Experimental Medicine 2014;7(12):5511.
  16. Khosravi Z, Sedaghat R, Baluchnejadmojarad T, Roghani M. Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation. International Immunopharmacology 2019;70:37-46.
  17. Samie A, Sedaghat R, Baluchnejadmojarad T, Roghani M. Hesperetin, a citrus flavonoid, attenuates testicular damage in diabetic rats via inhibition of oxidative stress, inflammation, and apoptosis. Life Sciences 2018;210:132-9.
  18. Mahmoud AM, Hussein OE, Hozayen WG, Bin-Jumah M, Abd El-Twab SM. Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats. Environmental Science and Pollution Research 2020;27(8):7910-21.
  19. Roghani M, Kalantari H, Khodayar MJ, Khorsandi L, Kalantar M, Goudarzi M, et al. Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity. rug Design, Development and Therapy 2020;14:1933-41.
  20. Kurt A, Tumkaya L, Turut H, Cure MC, Cure E, Kalkan Y, et al. Efectos protectores de infliximab sobre el daño pulmonar inducido por metotrexato. Archivos de Bronconeumología 2015;51(11):551-7.
  21. Çetin ES, Tetiker H, Çelik Öİ, Yılmaz N, Ciğerci İH. Methotrexate-induced nephrotoxicity in rats: protective effect of mistletoe (Viscum album L.) extract. Complementary Medicine Research 2017;24(6):364-70.
  22. Sarihan KK, Yilmaz MY, Eraldemir FC, Yazir Y, Acar E. Protective effects of apocynin on damaged testes of rats exposed to methotrexate. Turkish Journal of Medical Sciences 2020;50(5):1409-20.
  23. Salimi A, Pirhadi R, Jamali Z, Ramazani M, Yousefsani B, Pourahmad J. Mitochondrial and lysosomal protective agents ameliorate cytotoxicity and oxidative stress induced by cyclophosphamide and methotrexate in human blood lymphocytes. Human & Experimental Toxicology 2019;38(11):1266-74.
  24. AlBasher G, AlKahtane AA, Saud Alarifi DA, Alessia MS, Almeer RS, Abdel-Daim MM, et al. Methotrexate-induced apoptosis in human ovarian adenocarcinoma SKOV-3 cells via ROS-mediated bax/bcl-2-cyt-c release cascading. OncoTargets and Therapy 2019;12:21.
  25. Sanjeev S, Devi MS, Maurya K, Roy V, Gurusubramanian G, editors. Diosgenin: Therapeutic Action, Pharmacology and Applications 2017.
  26. Zhao H, Zhang X, Zhang B, Qu X. Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities. Open Life Sciences 2021;16(1):719-27.
  27. Binesh A, Devaraj SN, Halagowder D. Atherogenic diet induced lipid accumulation induced NFκB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent. Life sciences 2018;196:28-37.