Experimental study of renal toxicity of cyclosporine and the ameliorative effect of N-acetylecysteine in albino rat

Mai Abdelkader,Hoda Elsayed,Maha Hilal,Abdel Rahman Torky,Walaa Allam

doi:10.21608/ajfm.2021.174400

Abstract

Introduction: Cyclosporine A (CsA) is considered powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and also used in autoimmune diseases. However, its use is limited by many side effects mainly nephrotoxicity. NAC is an antioxidant found to reduce CsA toxicity. Aim of the work: The study aims to determine the effect of exposure to cyclosporine on the kidney and to investigate the protective role of NAC. Methods: the study conducted on 50 adult male albino rats for 4 weeks, divided into 5 groups, group A the negative control group, group B the olive oil group (0.5 ml/d orally), group C the cyclosporine group (25mg/kg/d orally), group D the NAC group (600mg/kg/d orally) and group E the cyclosporine+NAC group. At the end of the study the evaluation was done by biochemical analysis and histopathology. Results: cyclosporine significantly affects the kidney by morphological changes in the form of dilatation of urinary space with congestion and lobulation of glomerullar capillaries in the renal corpusle. Proximal convoluted tubules showed degeneration of their cells with irregularity and destruction of brush border. Degeneration of distal convoluted tubules with exfoliation of some cells inside the lumen and the peritubular capillaries were congested and extravasated. Also cyclosporine affects the kidney by increasing serum urea and creatinine levels, while coadministration of NAC with cyclosporine attenuate its effects. Conclusion: cyclosporine causes renal injury through oxidative stress and NAC as an antioxidant attenuates but not fully protect against cyclosporine induced injuries.

Highlights

Cyclosporine A (CsA) is considered powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and used in autoimmune diseases
There are many immunosuppressive agents used in transplant medicine one of them is cyclosporine A (CsA) which is a neutral agent that is derived from Cylindrocarpon lucidum Booth and Tolypocladium inflatum Gams fungi
Combination of NAC with cyclosporine showed no significant increase in the mean value of serum urea compaired to negative control group, positive control group and NAC treated group

Summary

Introduction

Cyclosporine A (CsA) is considered powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and used in autoimmune diseases. Aim of the work: The study aims to determine the effect of exposure to cyclosporine on the kidney and to investigate the protective role of NAC. Degeneration of distal convoluted tubules with exfoliation of some cells inside the lumen and the peritubular capillaries were congested and extravasated. Cyclosporine affects the kidney by increasing serum urea and creatinine levels, while coadministration of NAC with cyclosporine attenuate its effects. Conclusion: cyclosporine causes renal injury through oxidative stress and NAC as an antioxidant attenuates but not fully protect against cyclosporine induced injuries. Cyclosporine A suppress the synthesis of many cytokines as interleukin IL-2, IL-4, interferon-g and granulocyte-macrophage colony stimulating factor which are responsible of T cells activation (Damaino et al, 2015)

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Conclusion