{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:59:18Z","timestamp":1778155158177,"version":"3.51.4"},"reference-count":56,"publisher":"Wiley","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology","award":["SFRH\/BD\/63962\/2009"],"award-info":[{"award-number":["SFRH\/BD\/63962\/2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p>Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>6<\/mml:mn><\/mml:math>) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson\u2019s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-<jats:italic>\u03b2<\/jats:italic>, NF-<jats:italic>\u03ba<\/jats:italic><jats:italic>\u03b2<\/jats:italic>, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-<jats:italic>\u03b2<\/jats:italic>and IL-7, TBARs clearance, and kidney TGF-<jats:italic>\u03b2<\/jats:italic>and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent\/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL.<\/jats:p>","DOI":"10.1155\/2014\/576929","type":"journal-article","created":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T21:16:43Z","timestamp":1400534203000},"page":"1-17","source":"Crossref","is-referenced-by-count":9,"title":["Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers"],"prefix":"10.1155","volume":"2014","author":[{"given":"Jos\u00e9","family":"Sereno","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology & Experimental Therapeutics, IBILI, Faculty of Medicine, University of Coimbra, Sub-Unit 1 (P\u00f3lo III), 3000-548 Coimbra, Portugal"},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, 3000-548 Coimbra, 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