Effect of Infliximab on Renal Injury Due to Methotrexate in Rat

Authors

  • Aynur Kirbas Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Medine Cumhur Cure Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Yildiray Kalkan Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Erkan Cure Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Levent Tumkaya Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Osman Zikrullah Sahin Department of Nephrology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Suleyman Yuce Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Bayram Kizilkaya Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author
  • Ahmet Pergel Department of Surgery, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Author

Abstract

Introduction. Methotrexate, an antagonist of folic acid used in the treatment of many cancers and inflammatory diseases, is associated with side effects that limit its usage. Infliximab has been reported to have a protective effect against nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to investigate whether infliximab has a protective effect against methotrexate-induced nephrotoxicity.

Materials and Methods. We administered methotrexate at a dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg, intraperitoneally (infliximab group). The methotrexate and infliximab group received a similar single injection of infliximab 72 hours prior to methotrexate injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was administered intraperitoneally. Five days after methotrexate injection, blood samples were collected and the kidney tissues were removed for biochemical and histological examination.

Results. The methotrexate group had significantly higher tissue levels of tumor necrosis factor-α (P = .008), interleukin-1β (P = .036), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the methotrexate and infliximab group after the 5-day study. The methotrexate group also had significantly higher total histological scores (P < .001) and carbonic anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab group.

Conclusions. Infliximab has a strong protective effect against methotrexate-induced nephrotoxicity by suppressing cytokines release. It may decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II enzyme activities and slowing down purine metabolism.

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Author Biographies

  • Aynur Kirbas, Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    biochemistry
  • Medine Cumhur Cure, Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    biochemistry
  • Yildiray Kalkan, Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    histology
  • Erkan Cure, Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    internal medicine
  • Levent Tumkaya, Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    histology
  • Osman Zikrullah Sahin, Department of Nephrology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    nephrology
  • Suleyman Yuce, Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    internal medicine
  • Bayram Kizilkaya, Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
    internal medicine

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Published

2015-04-29

Issue

Section

ORIGINAL | Kidney Diseases

How to Cite

Effect of Infliximab on Renal Injury Due to Methotrexate in Rat. (2015). Iranian Journal of Kidney Diseases, 9(3), 221-229. https://www.ijkd.org/index.php/ijkd/article/view/1776