Iranian Journal of Veterinary Surgery

Iranian Journal of Veterinary Surgery

The Study of the Protective Effects of Fargesin on Experimental Ischemia-Reperfusion Injury of Liver in Male Rats

Document Type : Original Article

Authors
Department of Pathobiology, TaMS.C., Islamic Azad University, Tabriz, Iran.
Abstract
Reperfusion following ischemia can lead to metabolic and structural damage to the liver. Fargesin, known for its anti-inflammatory properties, holds potential applications in the development of drugs targeting inflammatory disorders. Most recent studies on fargesin have focused on its anti-inflammatory effects. This study aimed to evaluate the effects of fargesin on liver function, as well as its antioxidant and inflammatory status, following the induction of ischemia-reperfusion injury in the liver of rats. For this purpose, 40 male Wistar rats were randomly divided into four groups of 10: (1) Sham group: rats without any surgical intervention, (2) Surgical control group: rats subjected to surgery without ischemia-reperfusion, (3) Ischemia-reperfusion group: rats exposed to ischemia followed by 45 minutes of reperfusion, and (4) Ischemia-reperfusion with fargesin treatment group: rats that received fargesin at a dose of 50 mg/kg P.O via gavage for 12 weeks post-ischemia. Blood and liver tissue samples were collected, and the animals were sacrificed. Levels of serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were measured. In the liver tissue homogenates, levels of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were assessed. Histopathological examination of liver tissue was performed using light microscopy. In group 4, fargesin significantly (p < 0.05) reduced elevated levels of liver damage marker enzymes, decreased lipid peroxidation, and restored diminished antioxidant levels in the liver. Additionally, histopathological changes in the livers of fargesin-treated rats were significantly ameliorated. The results suggest that fargesin, with its anti-inflammatory properties, exhibits protective effects against ischemia-reperfusion-induced liver injury and could be a potential therapeutic agent for managing ischemia-reperfusion-related liver damage.
Keywords

Subjects


  1. Shin T, Kuboki S, Huber N, Eismann T, Galloway E, Schuster R, Blanchard J, Pritts TA, Lentsch AB. Activation of peroxisome proliferator-activated receptor-γ during hepatic ischemia is age-dependent. Journal of Surgical Research. 2008; 147(2): 200-205. doi: 10.1016/j.jss.2008.02.004
  2. van Gulik TM, de Graaf W, Dinant S, Busch OR, Gouma DJ. Vascular occlusion techniques during liver resection. Digestive Surgery. 2007; 24(4): 274-281. doi: 10.1159/000103658
  3. He XS, Ma Y, Wu LW, Wu JL, Hu RD, Chen GH, Huang JF. Dynamical changing patterns of glycogen and enzyme histochemical activities in rat liver graft undergoing warm ischemia injury. World Journal of Gastroenterology. 2005; 11(17): 2662. doi: 10.3748/wjg.v11.i17.2662
  4. Hassan‐Khabbar S, Cottart CH, Wendum D, Vibert F, Clot JP, Savouret JF, Conti M, Nivet‐Antoine V. Postischemic treatment by trans‐resveratrol in rat liver ischemia‐reperfusion: a possible strategy in liver surgery. Liver Transplantation. 2008; 14(4): 451-459. doi: 10.1002/lt.21405
  5. Shen SQ, Zhang Y, Xiang JJ, Xiong CL. Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes. World Journal of Gastroenterology. 2007; 13(13): 1953. doi: 10.3748/wjg.v13.i13.1953
  6. Pulitano C, Aldrighetti L. The protective role of steroids in ischemia-reperfusion injury of the liver. Current Pharmaceutical Design. 2008; 14(5): 496-503. doi: 10.2174/138161208783597353
  7. Polat KY, Aydinli BÜ, Polat O, Aydin U, Yazici P, Ozturk G, Gundogdu C, Kiziltunc A. The protective effect of aprotinin and α-tocopherol on ischemia-reperfusion injury of the rat liver. Transplantation Proceedings. 2008; 40(1): 63-68. doi: 10.1016/j.transproceed.2007.11.047
  8. Soares RO, Losada DM, Jordani MC, Évora P, Castro-e-Silva O. Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. International Journal of Molecular Sciences. 2019; 20(20): 5034. doi: 10.3390/ijms20205034
  9. Barber DA, Harris SR. Oxygen free radicals and antioxidants: a review: the use of antioxidant vitamin supplements to scavenge free radicals could decrease the risk of disease. American Pharmacy. 1994; 34(9): 26-35. doi: 10.1016/S0160-3450(15)30310-X
  10. Chun HW, Kim SJ, Pham TH, Bak Y, Oh J, Ryu HW, Oh SR, Hong JT, Yoon DY. Epimagnolin A inhibits IL‐6 production by inhibiting p38/NF‐κB and AP‐1 signaling pathways in PMA‐stimulated THP‐1 cells. Environmental Toxicology. 2019; 34(7): 796-803. doi: 10.1002/tox.22746
  11. Lu J, Zhang H, Pan J, Hu Z, Liu L, Liu Y, Yu X, Bai X, Cai D, Zhang H. Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways. Arthritis Research and Therapy. 2021; 23(1): 142. doi: 10.1186/s13075-021-02512-z
  12. Fu T, Chai B, Shi Y, Dang Y, Ye X. Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways. Journal of Dermatological Science. 2019; 94(1): 213-219. doi: 10.1016/j.jdermsci.2019.03.004
  13. Gedik E, Girgin S, Ozturk H, Obay BD, Ozturk H, Buyukbayram H. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats. World Journal of Gastroenterology. 2008; 14(46): 7101. doi: 10.3748/wjg.14.7101
  14. Cattozzo G, Calonaci A, Albeni C, Guerra E, Franzini M, Ghezzi F, Ceriotti F. Reference values for alanine aminotransferase, α-amylase, aspartate aminotransferase, γ-glutamyltransferase and lactate dehydrogenase measured according to the IFCC standardization during uncomplicated pregnancy. Clinical Chemistry and Laboratory Medicine. 2013; 51(10): e239-241. doi: 10.1515/cclm-2013-0371
  15. Babaei H, Mansouri-Najand L, Molaei MM, Kheradmand A, Sharifan M. Assessment of lactate dehydrogenase, alkaline phosphatase and aspartate aminotransferase activities in cow’s milk as an indicator of subclinical mastitis. Veterinary Research Communications. 2007; 31(4): 419-425. doi: 10.1007/s11259-007-3539-x
  16. Fraga CG, Leibovitz BE, Tappel AL. Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free Radical Biology and Medicine. 1988; 4(3): 155-161. doi: 10.1016/0891-5849(88)90023-8
  17. Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and Biophysical Research Communications. 1972; 46(2): 849-854. doi: 10.1016/S0006-291X(72)80218-3
  18. Claiborne A. Catalase activity In: CRC Handbook of Methods for Oxygen Radical Research. CRC Press, Boca Raton, Florida, 1985; 99: 283-284.
  19. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra W. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973; 179(4073): 588-590. doi: 10.1126/science.179.4073.588
  20. Mohandas J, Marshall JJ, Duggin GG, Horvath JS, Tiller DJ. Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Research. 1984; 44(11): 5086-5091.
  21. Frei A, Zimmermann A, Weigand K. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease. Hepatology. 1984; 4(5): 830-834. doi: 10.1002/hep.1840040505
  22. Yildiz F, Coban S, Terzi A, Ates M, Aksoy N, Cakir H, Ocak AR, Bitiren M. Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver. World Journal of Gastroenterology. 2008; 14(33): 5204. doi: 10.3748/wjg.14.5204
  23. Curtis SJ, Moritz M, Snodgrass PJ. Serum Enzymes Derived from Liver Cell Fractions: I. The response to carbon tetrachloride intoxication in rats. Gastroenterology. 1972; 62(1): 84-92. doi: 10.1016/S0016-5085(72)80012-X
  24. Qiao M, Peng Y, Yan T, Liu J, Yue J, Zhu Q, Peng X, Xiong S, Wen G. Fargesin exerts neuroprotective effect against cerebral ischemia/reperfusion injury in rats via alteration of NF‐κB signaling pathway. Journal of Biochemical and Molecular Toxicology. 2025; 39(7): e70354. doi: 10.1002/jbt.70354
  25. Tang SP, Mao XL, Chen YH, Yan LL, Ye LP, Li SW. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Frontiers in Immunology. 2022; 13: 870239. doi: 10.3389/fimmu.2022.870239
  26. Chance B, Greenstein DS, Roughton FJ. The mechanism of catalase action. I. Steady-state analysis. Archives of Biochemistry and Biophysics. 1952; 37(2): 301-321. doi: 10.1016/0003-9861(52)90194-X
  27. Naik SR, Panda VS. Hepatoprotective effect of Ginkgoselect Phytosome® in rifampicin induced liver injurym in rats: evidence of antioxidant activity. Fitoterapia. 2008; 79(6): 439-445. doi: 10.1016/j.fitote.2008.02.013

  • Receive Date 14 January 2025
  • Revise Date 02 June 2025
  • Accept Date 16 July 2025
  • First Publish Date 16 July 2025