The effect of immunosuppressive treatment during pregnancy on the activity of antioxidant enzymes in selected visceral organs among the offspring of wistar rats

Abstract

Kidney transplantation remains the treatment of choice in end-stage kidney disease. The introduction of new immunosuppressive drugs has significantly extended survival time in individuals after KTx, together with improving their quality of life. As a consequence, the number of women planning motherhood after kidney transplantation is also increasing. Despite strict specialist control, such pregnancies are still considered high-risk, as the impact of immunosuppressive drugs on fetal development is very significant. This study evaluates the effect of most common immunosuppressive treatment schemes on the indicators of oxidative stress in in the intestines and spleen in an animal model, using Wistar rats. All drugs were administered to pregnant females by a gastric tube in weight- adjusted doses. Initially, a full dose was used, but this resulted in severe fetal damage in the majority of rats, grouped according to drug regimens. The experiment was then repeated with the doses reduced by half, finally obtaining a sufficient number of progeny animals for the study. The research demonstrated alterations in the activity of antioxidant enzymes and concentrations of reduced glutathione in all groups of offspring rats whose mothers received immunosuppressive treatment during pregnancy. Results varied depending on the regimen and drug doses 27 used. Within the group treated with the full dose of cyclosporine A, mycophenolate mofetil, and prednisone a significant increase in the activity of antioxidant enzymes in the spleen occured. In the tacrolimus and mycophenolate mofetil (reduced-dose) group, a variety of changes were observed in all tissues and organs examined. In the group receiving cyclosporine A, mycophenolate mofetil and prednisone at a reduced dose as well as in the group receiving cyclosporine A, everolimus and prednisone at a reduced dose, an increase in the activity of antioxidant enzymes was demonstrated, mainly in the small intestine