Glatiramer acetate attenuates renal ischemia reperfusion injury in rat model.

Abstract

Chronic renal failure can ultimately lead to kidney transplantation. Renal transplantation is associated with ischemia-reperfusion injury (I/R).2 The subsequent processes of kidney I/R can lead to irreversible damages to the kidney tissue. Glatiramer acetate is an immunomodulatory drug for the treatment of multiple sclerosis (MS) and the anti-inflammatory effects of this drug have already been proven in some inflammatory models. The purpose of this study was to evaluate the protective effects of Glatiramer on reducing the damages arising from kidney ischemia-reperfusion. In this study, 35 Wistar rats were used which divided into 5 groups: sham, control (I/R), I/R + Glatiramer 0.5 mg/kg, I/R + Glatiramer 1 mg/kg, I/R + Glatiramer 2 mg/kg. Renal arteries were clamped bilaterally for 45 min, then the clamps were removed and the reperfusion process continued to 24 h. In the following, serum and kidneys were separated for analysis. In the control group, serum levels of LDH, inflammatory factor TNF-α and renal functional markers such as BUN and Creatinine were remarkably increased, but in the treatment groups, especially in Glatiramer 2 mg/kg received group, a significant decrease in these factors was observed. Tissue concentration of MDA was reduced following Glatiramer treatment. Besides, Glatiramer attenuated the increased kidney level of NF-κB protein using immunohistochemical assay. NFkB migration to the nucleolus increases inflammatory cytokines production. The anti-inflammatory factor, IL-10, in serum was significantly increased in the treatment group of Glatiramer 2 mg/kg. Furthermore, Glatiramer decreased renal tissue injury score according to the histopathological study. These results demonstrate that Glatiramer may play protective effects in kidney ischemia-reperfusion injury by reducing inflammatory and oxidative damages.

• Authors: Sadaf Nezamoleslami, Mohammad Sheibani, Ahmad Reza Dehpour, Parnia Mobasheran, Hamed Shafaroodi
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 112 Pg. 104329 (02 2020) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 31697931 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• NF-kappa B
• RELA protein, human
• Rela protein, rat
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Malondialdehyde
• Glatiramer Acetate
• Creatinine

Topics

• Acute Kidney Injury (drug therapy, pathology)
• Animals
• Apoptosis (drug effects)
• Creatinine (metabolism)
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Glatiramer Acetate (pharmacology)
• Humans
• Interleukin-10 (genetics)
• Kidney (drug effects, pathology)
• Malondialdehyde (metabolism)
• NF-kappa B (genetics)
• Oxidative Stress (drug effects)
• Rats
• Reperfusion Injury (drug therapy, pathology)
• Transcription Factor RelA (genetics)
• Tumor Necrosis Factor-alpha (genetics)