{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:37:44Z","timestamp":1760240264900,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijerph16081370","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T03:02:01Z","timestamp":1555470121000},"page":"1370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Effects of Short-Term Immunosuppressive Therapy on Redox Parameters in the Livers of Pregnant Wistar Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-7902","authenticated-orcid":false,"given":"Dagmara","family":"Szypulska-Koziarska","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Wilk","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Kabat-Koperska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Kolasa-Wo\u0142osiuk","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta","family":"Wolska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Human Nutrition, Pomeranian Medical University in Szczecin, Broniewskiego 24, 71-460 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Wiszniewska","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Pomeranian Medical University in Szczecin, Powst. 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Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s13105-015-0451-7","article-title":"Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats","volume":"72","author":"Ferjani","year":"2016","journal-title":"J. Physiol. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1146\/annurev.immunol.15.1.707","article-title":"Transcription factors of the NFAT family: Regulation and function","volume":"15","author":"Rao","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1016\/j.transproceed.2008.08.028","article-title":"Tacrolimus-induced apoptotic signal transduction pathway","volume":"40","author":"Choi","year":"2008","journal-title":"Transplant. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tcb.2010.09.011","article-title":"Interaction of calcineurin with substrates and targeting proteins","volume":"21","author":"Li","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.proghi.2004.04.001","article-title":"Cyclosporine A and adverse effects on organs: Histochemical studies","volume":"39","author":"Rezzani","year":"2004","journal-title":"Prog. Histochem. Cytochem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Weber, N.T., Sigaroudi, A., Ritter, A., Boss, A., Lehmann, K., Goodman, D., Farese, S., Weiler, S., and Mueller, T.F. (2017). Intractable ascites associated with mycophenolate in a simultaneous kidney-pancreas transplant patient: A case report. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0757-5"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.14701\/ahbps.2018.22.1.19","article-title":"A cross-sectional analysis of long-term immunosuppressive regimens after liver transplantation at Asan Medical Center: Increased preference for mycophenolate mofetil","volume":"22","author":"Hwang","year":"2018","journal-title":"Ann. Hepatobiliary Pancreat. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1136\/gut.2003.024927","article-title":"Developments in liver transplantation","volume":"53","author":"Neuberger","year":"2004","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.etp.2008.04.007","article-title":"Oral L-arginine protects against cyclosporine-induced hepatotoxicity in rats","volume":"60","author":"Kurus","year":"2008","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6932","DOI":"10.1073\/pnas.1816734116","article-title":"Development of highly potent glucocorticoids for steroid-resistant severe asthma","volume":"116","author":"He","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","first-page":"Cd007606","article-title":"Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients","volume":"4","author":"Fairfield","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.intimp.2005.03.021","article-title":"Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver","volume":"5","author":"Rezzani","year":"2005","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.chemphyslip.2019.03.011","article-title":"Biological effect of protein modifications by lipid peroxidation products","volume":"221","author":"Gegotek","year":"2019","journal-title":"Chem. Phys. Lipids"},{"key":"ref_16","first-page":"44","article-title":"Protection against oxidative stress in male reproductive system","volume":"62","author":"Marchlewicz","year":"2016","journal-title":"Pomeranian J. Life Sci."},{"key":"ref_17","first-page":"66","article-title":"Evidence for lipid peroxidation by paraquat in the perfused rat lung","volume":"101","author":"Aldrich","year":"1983","journal-title":"J. Lab. Clin. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Linares, I., Hamar, M., Selzner, N., and Selzner, M. (2018). Steatosis in Liver Transplantation: Current Limitations and Future Strategies. Transplantation.","DOI":"10.1097\/TP.0000000000002466"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e80","DOI":"10.1159\/000209208","article-title":"Metabolic profiles in urine reflect nephrotoxicity of sirolimus and cyclosporine following rat kidney transplantation","volume":"111","author":"Schmitz","year":"2009","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.4103\/1319-2442.128512","article-title":"Protective effect of everolimus on renal ischemia reperfusion injury in rats","volume":"25","author":"Sagiroglu","year":"2014","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/TP.0b013e3182421604","article-title":"Drug interaction between cyclosporine and mTOR inhibitors in experimental model of chronic cyclosporine nephrotoxicity and pancreatic islet dysfunction","volume":"93","author":"Piao","year":"2012","journal-title":"Transplantation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/j.1432-2277.2008.00710.x","article-title":"Effect of mTOR inhibitor on body weight: From an experimental rat model to human transplant patients","volume":"21","author":"Rovira","year":"2008","journal-title":"Transpl. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1046\/j.1523-1755.2001.0590051663.x","article-title":"Effect of prenatal dexamethasone on rat renal development","volume":"59","author":"Ortiz","year":"2001","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/01.HYP.0000049763.51269.51","article-title":"Prenatal dexamethasone programs hypertension and renal injury in the rat","volume":"41","author":"Ortiz","year":"2003","journal-title":"Hypertension"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.yexcr.2004.07.002","article-title":"Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro","volume":"300","author":"Butzal","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1046\/j.1365-4362.2000.00948.x","article-title":"The effects of drugs on wound healing: Part 1","volume":"39","author":"Karukonda","year":"2000","journal-title":"Int. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.redox.2018.02.018","article-title":"Impact of carbonylation on glutathione peroxidase-1 activity in human hyperglycemic endothelial cells","volume":"16","author":"Sultan","year":"2018","journal-title":"Redox Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1872-034X.2007.00273.x","article-title":"Protective effects of a combination of quercetin and vitamin E against cyclosporine A-induced oxidative stress and hepatotoxicity in rats","volume":"38","author":"Zal","year":"2008","journal-title":"Hepatol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1600-6143.2011.03826.x","article-title":"Clinical outcomes in kidney transplant recipients receiving long-term therapy with inhibitors of the mammalian target of rapamycin","volume":"12","author":"Cortazar","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.envpol.2017.05.094","article-title":"Oxidative status in relation to metal pollution and calcium availability in pied flycatcher nestlings\u2014A calcium manipulation experiment","volume":"229","author":"Espin","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_31","first-page":"160","article-title":"Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside","volume":"15","author":"Arauz","year":"2016","journal-title":"Ann. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.numecd.2015.11.013","article-title":"Beneficial effects of omega-3 and vitamin E coadministration on gene expression of SIRT1 and PGC1alpha and serum antioxidant enzymes in patients with coronary artery disease","volume":"26","author":"Saboori","year":"2016","journal-title":"Nutr. Metab. Cardiovasc. 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