The Effects of Short-Term Immunosuppressive Therapy on Redox Parameters in the Livers of Pregnant Wistar Rats.

Szypulska-Koziarska Szypulska-Koziarska,Wolska Wolska,Kabat-Koperska Kabat-Koperska,Kolasa-Wołosiuk Kolasa-Wołosiuk,Wilk Wilk,Wiszniewska Wiszniewska

doi:10.3390/ijerph16081370

Szypulska-Koziarska Szypulska-Koziarska, Wolska Wolska + Show 4 more

Open Access

https://doi.org/10.3390/ijerph16081370

Copy DOI

Abstract

Immunosuppressive drugs are widely used to avoid graft rejection, but they are also known to be strongly hepatotoxic. The goal of the current study was to determine: (i) the immunoexpression of SOD1, CAT, GPX1; (ii) the concentration of MDA, GSH; (iii) the activity of SOD, CAT, GPX, in the native liver of a pregnant female rats undergoing immunosuppressive therapy. The study was based on archival material obtained from Department of Nephrology, Transplantology and Internal Medicine of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, Poland. The study was carried out on 32 female rats exposed to oral administration of immunosuppressants two weeks before and during pregnancy. The percentage of SOD1 immunopositive hepatocytes in rats treated with cyclosporine A, mycophenolate mofetil, everolimus, and glucocorticosteroid was significantly elevated above that of the control rats. The concentration of MDA in the liver of animals exposed to cyclosporine A, everolimus, and glucocorticosteroid was significantly higher than in other groups. Among the groups of dams treated with immunosuppressive drugs, the highest significant concentration of GSH was found in the livers of rats treated with cyclosporine A, mycophenolate mofetil and glucocorticosteroid. Immunosuppressive therapy during pregnancy affects the oxidoreductive balance in the livers of rats, depending on the regimen used.

Highlights

Following the transplantation of solid organs, the immune system of recipients engages in a range of mechanisms aimed at overcoming foreign agents, which can contribute to graft failure
The female rats were divided into 4 groups; one control, that did not receive any medicaments, and three experimental groups, that received the following immunosuppressive regimens: (i) CMG: cyclosporine A, mycophenolate mofetil, prednisone; (ii) TAC + mycophenalate mofetil (MMF) + G (TMG): tacrolimus, mycophenolate mofetil, prednisone; (iii) CEG: cyclosporine A, everolimus, prednisone
Immunosuppressive drugs are crucial for recipients who have received transplantations of solid organs, as they prolong the vitality of the graft, simultaneously prolonging the life of these patients

Summary

Introduction

Following the transplantation of solid organs, the immune system of recipients engages in a range of mechanisms aimed at overcoming foreign agents, which can contribute to graft failure. The rejection of allografts is mediated primarily by infiltration of the graft by T lymphocytes and the range of inflammatory reactions that arise due to their presence. The proliferation of mononuclear leukocytes, such as lymphocytes and monocytes, is a clear demonstration of acute and chronic rejection within the allograft [1]. Immunosuppressive drugs are widely used to avoid graft rejection, but it is well known that immunosuppressive drugs are strongly nephrotoxic and hepatotoxic [2,3]. Different immunosuppressants are prescribed in combinations of three drugs (each from a distinct group) after kidney transplantation. Calcineurin inhibitors (CNIs) are one of these groups, and include

Objectives

Methods

Discussion

Conclusion