{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:35:46Z","timestamp":1790390146292,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T00:00:00Z","timestamp":1714867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T00:00:00Z","timestamp":1714867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018778","name":"Al-Azhar University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018778","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and results<\/jats:title>\n            <jats:p>Thirty-two Sprague Dawley rats were treated with TAC (1.5\u00a0mg\/kg\/day, subcutaneously) and\/or Lina (5\u00a0mg\/kg\/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (\u03b1-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-\u03b21) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1\u03b1), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG),\u00a0as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Lina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11033-024-09533-2","type":"journal-article","created":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T13:01:36Z","timestamp":1714914096000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2\/HO-1 and HIF-1\u03b1\/CTGF\/PAI-1"],"prefix":"10.1007","volume":"51","author":[{"given":"Mohamed E.","family":"Nady","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola M. Abd","family":"El-Raouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El-Sayed M.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,5]]},"reference":[{"issue":"22","key":"9533_CR1","doi-asserted-by":"publisher","first-page":"8628","DOI":"10.3390\/ijms21228628","volume":"21","author":"JH Lim","year":"2020","unstructured":"Lim JH, Oh EJ, Oh SH, Jung HY, Choi JY, Cho JH, Park SH, Kim YL, Kim CD (2020) Renoprotective effects of alpha-1 antitrypsin against tacrolimus-induced renal Injury. Int J Mol Sci 21(22):8628. https:\/\/doi.org\/10.3390\/ijms21228628","journal-title":"Int J Mol Sci"},{"issue":"8","key":"9533_CR2","doi-asserted-by":"publisher","first-page":"862","DOI":"10.4240\/wjgs.v14.i8.862","volume":"14","author":"F Ahmed","year":"2022","unstructured":"Ahmed F, Zakaria F, Enebong Nya G, Mouchli M (2022) Sirolimus vs tacrolimus: which one is the best therapeutic option for patients undergoing liver transplantation for hepatocellular carcinoma? World J Gastrointest Surg 14(8):862\u2013866. https:\/\/doi.org\/10.4240\/wjgs.v14.i8.862","journal-title":"World J Gastrointest Surg"},{"issue":"4","key":"9533_CR3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1139\/cjpp-2020-0012","volume":"99","author":"IA Harb","year":"2021","unstructured":"Harb IA, Ashour H, Sabry D, El-Yasergy DF, Hamza WM, Mostafa A (2021) Nicorandil prevents the nephrotoxic effect of cyclosporine-A in albino rats through modulation of HIF-1\u03b1\/VEGF\/eNOS signaling. Can J Physiol Pharmacol 99(4):411\u2013417. https:\/\/doi.org\/10.1139\/cjpp-2020-0012","journal-title":"Can J Physiol Pharmacol"},{"issue":"1","key":"9533_CR4","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s12882-019-1399-6","volume":"20","author":"K Luo","year":"2019","unstructured":"Luo K, Lim SW, Jin J, Jin L, Gil HW, Im DS, Hwang HS, Yang CW (2019) Cilastatin protects against tacrolimus-induced nephrotoxicity via anti-oxidative and anti-apoptotic properties. BMC Nephrol 20(1):221. https:\/\/doi.org\/10.1186\/s12882-019-1399-6","journal-title":"BMC Nephrol"},{"key":"9533_CR5","doi-asserted-by":"publisher","first-page":"610102","DOI":"10.3389\/fphar.2020.610102","volume":"11","author":"P Gao","year":"2021","unstructured":"Gao P, Du X, Liu L, Xu H, Liu M, Guan X, Zhang C (2021) Astragaloside IV alleviates tacrolimus-induced chronic nephrotoxicity via p62-Keap1-Nrf2 pathway. Front Pharmacol 11:610102. https:\/\/doi.org\/10.3389\/fphar.2020.610102","journal-title":"Front Pharmacol"},{"issue":"5","key":"9533_CR6","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1055\/a-1369-8651","volume":"71","author":"SM Poormoosavi","year":"2021","unstructured":"Poormoosavi SM, Behmanesh MA, Abeyat H, Sangtarash E (2021) Evaluation of the effect of captopril and losartan on tacrolimus-induced nephrotoxicity in rats. Drug Res (Stuttg) 71(5):243\u2013249. https:\/\/doi.org\/10.1055\/a-1369-8651","journal-title":"Drug Res (Stuttg)"},{"issue":"6","key":"9533_CR7","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1016\/j.transproceed.2015.06.008","volume":"47","author":"JH Back","year":"2015","unstructured":"Back JH, Ryu HH, Hong R, Han SA, Yoon YM, Kim DH, Hong SJ, Kim HL, Chung JH, Shin BC, Kwon YE (2015) Antiproteinuric effects of green tea extract on tacrolimus-induced nephrotoxicity in mice. Transplant Proc 47(6):2032\u20132034. https:\/\/doi.org\/10.1016\/j.transproceed.2015.06.008","journal-title":"Transpl Proc"},{"issue":"4","key":"9533_CR8","doi-asserted-by":"publisher","first-page":"414","DOI":"10.23876\/j.krcp.19.063","volume":"38","author":"T Honda","year":"2019","unstructured":"Honda T, Hirakawa Y, Nangaku M (2019) The role of oxidative stress and hypoxia in renal disease. Kidney Res Clin Pract 38(4):414\u2013426. https:\/\/doi.org\/10.23876\/j.krcp.19.063","journal-title":"Kidney Res Clin Pract"},{"key":"9533_CR9","doi-asserted-by":"publisher","first-page":"6114132","DOI":"10.1155\/2021\/6114132","volume":"2021","author":"H Zhang","year":"2021","unstructured":"Zhang H, Xu R, Wang Z (2021) Contribution of oxidative stress to HIF-1-mediated profibrotic changes during the kidney damage. Oxid Med Cell Longev 2021:6114132. https:\/\/doi.org\/10.1155\/2021\/6114132","journal-title":"Oxid Med Cell Longev"},{"issue":"1","key":"9533_CR10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jphs.2017.12.004","volume":"136","author":"K Kabei","year":"2018","unstructured":"Kabei K, Tateishi Y, Nozaki M, Tanaka M, Shiota M, Osada-Oka M, Nishide S, Uchida J, Nakatani T, Tomita S, Miura K (2018) Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: special references to HIF-1 dependent gene expression of profibrogenic molecules. J Pharmacol Sci 136(1):31\u201338. https:\/\/doi.org\/10.1016\/j.jphs.2017.12.004","journal-title":"J Pharmacol Sci"},{"key":"9533_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13069-016-0038-0","volume":"9","author":"S Shi","year":"2016","unstructured":"Shi S, Koya D, Kanasaki K (2016) Dipeptidyl peptidase-4 and kidney fibrosis in diabetes. Fibrogenesis Tissue Repair 9:1. https:\/\/doi.org\/10.1186\/s13069-016-0038-0","journal-title":"Fibrogenesis Tissue Repair"},{"issue":"4","key":"9533_CR12","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1159\/000495517","volume":"141","author":"MA Oraby","year":"2019","unstructured":"Oraby MA, El-Yamany MF, Safar MM, Assaf N, Ghoneim HA (2019) Amelioration of early markers of diabetic nephropathy by linagliptin in fructose-streptozotocin-induced type 2 diabetic rats. Nephron 141(4):273\u2013286. https:\/\/doi.org\/10.1159\/000495517","journal-title":"Nephron"},{"issue":"20","key":"9533_CR13","doi-asserted-by":"publisher","first-page":"11190","DOI":"10.3390\/ijms222011190","volume":"22","author":"TJ Wu","year":"2021","unstructured":"Wu TJ, Hsieh YJ, Lu CW, Lee CJ, Hsu BG (2021) Linagliptin protects against endotoxin-induced acute kidney injury in rats by decreasing inflammatory cytokines and reactive oxygen species. Int J Mol Sci 22(20):11190. https:\/\/doi.org\/10.3390\/ijms222011190.","journal-title":"Int J Mol Sci"},{"key":"9533_CR14","doi-asserted-by":"publisher","first-page":"175498","DOI":"10.1016\/j.ejphar.2023.175498","volume":"941","author":"RZ ElGamal","year":"2023","unstructured":"ElGamal RZ, Tadros MG, Menze ET (2023) Linagliptin counteracts rotenone\u2019s toxicity in non-diabetic rat model of Parkinson\u2019s disease: insights into the neuroprotective roles of DJ-1, SIRT-1\/Nrf-2 and implications of HIF1-\u03b1. Eur J Pharmacol 941:175498. https:\/\/doi.org\/10.1016\/j.ejphar.2023.175498","journal-title":"Eur J Pharmacol"},{"issue":"8","key":"9533_CR15","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1007\/s00592-021-01681-2","volume":"58","author":"G Castoldi","year":"2021","unstructured":"Castoldi G, Carletti R, Ippolito S, Colzani M, Barzaghi F, Stella A, Zerbini G, Perseghin G, Zatti G, di Gioia CRT (2021) Sodium-glucose cotransporter 2 inhibition prevents renal fibrosis in cyclosporine nephropathy. Acta Diabetol 58(8):1059\u20131070. https:\/\/doi.org\/10.1007\/s00592-021-01681-2","journal-title":"Acta Diabetol"},{"issue":"8","key":"9533_CR16","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.3390\/ph16081065","volume":"16","author":"HH Arab","year":"2023","unstructured":"Arab HH, Eid AH, Alsufyani SE, Ashour AM, El-Sheikh AAK, Darwish HW, Georgy GS (2023) Neuroprotective impact of linagliptin against cadmium-induced cognitive impairment and neuropathological aberrations: targeting SIRT1\/Nrf2 axis, apoptosis, and autophagy. Pharmaceuticals (Basel) 16(8):1065. https:\/\/doi.org\/10.3390\/ph16081065","journal-title":"Pharmaceuticals (Basel)"},{"issue":"1","key":"9533_CR17","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41401-020-0449-8","volume":"42","author":"HL Zheng","year":"2021","unstructured":"Zheng HL, Zhang HY, Zhu CL, Li HY, Cui S, Jin J, Piao SG, Jiang YJ, Xuan MY, Jin JZ, Jin YS, Lee JP, Chung BH, Choi BS, Yang CW, Li C (2021) L-Carnitine protects against tacrolimus-induced renal injury by attenuating programmed cell death via PI3K\/AKT\/PTEN signaling. Acta Pharmacol Sin 42(1):77\u201387. https:\/\/doi.org\/10.1038\/s41401-020-0449-8","journal-title":"Acta Pharmacol Sin"},{"issue":"2","key":"9533_CR18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/laban.432","volume":"43","author":"A Sharma","year":"2014","unstructured":"Sharma A, Fish BL, Moulder JE, Medhora M, Baker JE, Mader M, Cohen EP (2014) Safety and blood sample volume and quality of a refined retro-orbital bleeding technique in rats using a lateral approach. Lab Anim (NY) 43(2):63\u201366. https:\/\/doi.org\/10.1038\/laban.432","journal-title":"Lab Anim (NY)"},{"issue":"2","key":"9533_CR19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/ckj\/sfs013","volume":"5","author":"S Uchino","year":"2012","unstructured":"Uchino S, Bellomo R, Goldsmith D (2012) The meaning of the blood urea nitrogen\/creatinine ratio in acute kidney injury. Clin Kidney J 5(2):187\u2013191. https:\/\/doi.org\/10.1093\/ckj\/sfs013","journal-title":"Clin Kidney J"},{"issue":"5","key":"9533_CR20","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.3390\/biomedicines10051106","volume":"10","author":"C Cuesta","year":"2022","unstructured":"Cuesta C, Fuentes-Calvo I, Sancho-Martinez SM, Valentijn FA, D\u00fcwel A, Hidalgo-Thomas OA, Ag\u00fceros-Blanco C, Benito-Hern\u00e1ndez A, Ramos-Barron MA, G\u00f3mez-Alamillo C, Arias M, Nguyen TQ, Goldschmeding R, Mart\u00ednez-Salgado C, L\u00f3pez-Hern\u00e1ndez FJ (2022) Urinary KIM-1 correlates with the subclinical sequelae of tubular damage persisting after the apparent functional recovery from intrinsic acute kidney injury. Biomedicines 10(5):1106. https:\/\/doi.org\/10.3390\/biomedicines10051106","journal-title":"Biomedicines"},{"issue":"1","key":"9533_CR21","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1006\/niox.2000.0319","volume":"5","author":"KM Miranda","year":"2001","unstructured":"Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5(1):62\u201371. https:\/\/doi.org\/10.1006\/niox.2000.0319","journal-title":"Nitric Oxide"},{"key":"9533_CR22","volume-title":"Bancroft\u2019s theory and practice of histological techniques","author":"KS Suvarna","year":"2012","unstructured":"Suvarna KS, Layton C, Bancroft JD (2012) Bancroft\u2019s theory and practice of histological techniques, 7th edn. Churchill Livingstone, New York","edition":"7"},{"key":"9533_CR23","doi-asserted-by":"publisher","first-page":"117082","DOI":"10.1016\/j.lfs.2019.117082","volume":"239","author":"SM Abd El-Lateef","year":"2019","unstructured":"Abd El-Lateef SM, El-Sayed EM, Mansour AM, Salama SA (2019) The protective role of estrogen and its receptors in gentamicin-induced acute kidney injury in rats. Life Sci 239:117082. https:\/\/doi.org\/10.1016\/j.lfs.2019.117082","journal-title":"Life Sci"},{"key":"9533_CR24","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248\u2013254. https:\/\/doi.org\/10.1016\/0003-2697(76)90527-3","journal-title":"Anal Biochem"},{"issue":"6","key":"9533_CR25","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.3390\/ijerph16061044","volume":"16","author":"C Park","year":"2019","unstructured":"Park C, Kwon DH, Hwang SJ, Han MH, Jeong JW, Hong SH, Cha HJ, Hong SH, Kim GY, Lee HJ, Kim S, Kim HS, Choi YH (2019) Protective effects of Nargenicin A1 against Tacrolimus-Induced oxidative stress in Hirame Natural embryo cells. Int J Environ Res Public Health 16(6):1044. https:\/\/doi.org\/10.3390\/ijerph16061044","journal-title":"Int J Environ Res Public Health"},{"issue":"3","key":"9533_CR26","doi-asserted-by":"publisher","first-page":"393","DOI":"10.3904\/kjim.2022.293","volume":"38","author":"L Jin","year":"2023","unstructured":"Jin L, Shen N, Wen X, Wang W, Lim SW, Yang CW (2023) CTLA4-Ig protects tacrolimus-induced oxidative stress via inhibiting the AKT\/FOXO3 signaling pathway in rats. Korean J Intern Med 38(3):393\u2013405. https:\/\/doi.org\/10.3904\/kjim.2022.293","journal-title":"Korean J Intern Med"},{"key":"9533_CR27","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.toxlet.2021.01.020","volume":"341","author":"R Fu","year":"2021","unstructured":"Fu R, Tajima S, Shigematsu T, Zhang M, Tsuchimoto A, Egashira N, Ieiri I, Masuda S (2021) Establishment of an experimental rat model of tacrolimus-induced kidney injury accompanied by interstitial fibrosis. Toxicol Lett 341:43\u201350. https:\/\/doi.org\/10.1016\/j.toxlet.2021.01.020","journal-title":"Toxicol Lett"},{"issue":"4","key":"9533_CR28","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1111\/bph.15320","volume":"178","author":"AL Mayer","year":"2021","unstructured":"Mayer AL, Scheitacker I, Ebert N, Klein T, Amann K, Daniel C (2021) The dipeptidyl peptidase 4 inhibitor linagliptin ameliorates renal injury and accelerated resolution in a rat model of crescentic nephritis. Br J Pharmacol 178(4):878\u2013895. https:\/\/doi.org\/10.1111\/bph.15320","journal-title":"Br J Pharmacol"},{"issue":"4","key":"9533_CR29","doi-asserted-by":"publisher","first-page":"651","DOI":"10.4103\/0377-4929.72015","volume":"53","author":"A Sharma","year":"2010","unstructured":"Sharma A, Jain S, Gupta R, Guleria S, Agarwal S, Dinda A (2010) Calcineurin inhibitor toxicity in renal allografts: morphologic clues from protocol biopsies. Indian J Pathol Microbiol 53(4):651\u2013657. https:\/\/doi.org\/10.4103\/0377-4929.72015","journal-title":"Indian J Pathol Microbiol"},{"issue":"2","key":"9533_CR30","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nrneph.2015.215","volume":"12","author":"D Zhou","year":"2016","unstructured":"Zhou D, Liu Y (2016) Renal fibrosis in 2015: understanding the mechanisms of kidney fibrosis. Nat Rev Nephrol 12(2):68\u201370. https:\/\/doi.org\/10.1038\/nrneph.2015.215","journal-title":"Nat Rev Nephrol"},{"issue":"5","key":"9533_CR31","doi-asserted-by":"publisher","first-page":"F433","DOI":"10.1152\/ajprenal.00226.2022","volume":"324","author":"AC Ume","year":"2023","unstructured":"Ume AC, Wenegieme TY, Shelby JN, Paul-Onyia CDB, Waite AMJ 3rd, Kamau JK, Adams DN, Susuki K, Bennett ES, Ren H, Williams CR (2023) Tacrolimus induces fibroblast-to-myofibroblast transition via a TGF-\u03b2-dependent mechanism to contribute to renal fibrosis. Am J Physiol Ren Physiol 324(5):F433\u2013F445. https:\/\/doi.org\/10.1152\/ajprenal.00226.2022","journal-title":"Am J Physiol Ren Physiol"},{"issue":"3","key":"9533_CR32","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/ki.2015.103","volume":"88","author":"S Shi","year":"2015","unstructured":"Shi S, Srivastava SP, Kanasaki M, He J, Kitada M, Nagai T, Nitta K, Takagi S, Kanasaki K, Koya D (2015) Interactions of DPP-4 and integrin \u03b21 influences endothelial-to-mesenchymal transition. Kidney Int 88(3):479\u2013489. https:\/\/https:\/\/doi.org\/10.1038\/ki.2015.103","journal-title":"Kidney Int"},{"issue":"1","key":"9533_CR33","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/art.41058","volume":"72","author":"A Soare","year":"2020","unstructured":"Soare A, Gy\u00f6rfi HA, Matei AE, Dees C, Rauber S, Wohlfahrt T, Chen CW, Ludolph I, Horch RE, B\u00e4uerle T, von H\u00f6rsten S, Mihai C, Distler O, Ramming A, Schett G, Distler JHW (2020) Dipeptidylpeptidase 4 as a marker of activated fibroblasts and a potential target for the treatment of fibrosis in systemic sclerosis. Arthritis Rheumatol 72(1):137\u2013149. https:\/\/doi.org\/10.1002\/art.41058","journal-title":"Arthritis Rheumatol"},{"key":"9533_CR34","doi-asserted-by":"publisher","first-page":"172844","DOI":"10.1016\/j.ejphar.2019.172844","volume":"867","author":"F Bai","year":"2020","unstructured":"Bai F, Zhang LH, Zhang WW, Zheng RH, Eskew JR, Bennett J, Wang NP, Bose HS, Zhao ZQ (2020) Conservation of glucagon like peptide-1 level with liraglutide and linagilptin protects the kidney against angiotensin II-induced tissue fibrosis in rats. Eur J Pharmacol 867:172844. https:\/\/doi.org\/10.1016\/j.ejphar.2019.172844","journal-title":"Eur J Pharmacol"},{"key":"9533_CR35","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.etap.2019.03.018","volume":"69","author":"AAK El-Sheikh","year":"2019","unstructured":"El-Sheikh AAK, Morsy MA, Abdel-Latif RG (2019) Modulation of eNOS\/iNOS by nebivolol protects against cyclosporine A-mediated nephrotoxicity through targeting inflammatory and apoptotic pathways. Environ Toxicol Pharmacol 69:26\u201335. https:\/\/doi.org\/10.1016\/j.etap.2019.03.018","journal-title":"Environ Toxicol Pharmacol"},{"issue":"3","key":"9533_CR36","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1089\/ars.2016.6665","volume":"25","author":"BB Ratliff","year":"2016","unstructured":"Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS (2016) Oxidant mechanisms in Renal Injury and Disease. Antioxid Redox Signal 25(3):119\u2013146. https:\/\/doi.org\/10.1089\/ars.2016.6665","journal-title":"Antioxid Redox Signal"},{"issue":"4","key":"9533_CR37","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00210-019-01765-5","volume":"393","author":"WY Abdelzaher","year":"2020","unstructured":"Abdelzaher WY, Rofaeil RR, Ali DME, Attya ME (2020) Protective effect of dipeptidyl peptidase-4 inhibitors in testicular torsion\/detorsion in rats: a possible role of HIF-1\u03b1 and nitric oxide. Naunyn Schmiedebergs Arch Pharmacol 393(4):603\u2013614. https:\/\/doi.org\/10.1007\/s00210-019-01765-5","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"9533_CR38","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1159\/000449289","volume":"135","author":"HS Kim","year":"2017","unstructured":"Kim HS, Lim SW, Jin L, Jin J, Chung BH, Yang CW (2017) The protective effect of febuxostat on chronic tacrolimus-induced nephrotoxicity in rats. Nephron 135(1):61\u201371. https:\/\/doi.org\/10.1159\/000449289","journal-title":"Nephron"},{"key":"9533_CR39","doi-asserted-by":"publisher","first-page":"175048","DOI":"10.1016\/j.ejphar.2022.175048","volume":"927","author":"TE Banks","year":"2022","unstructured":"Banks TE, Rajapaksha M, Zhang LH, Bai F, Wang NP, Zhao ZQ (2022) Suppression of angiotensin II-activated NOX4\/NADPH oxidase and mitochondrial dysfunction by preserving glucagon-like peptide-1 attenuates myocardial fibrosis and hypertension. Eur J Pharmacol 927:175048. https:\/\/doi.org\/10.1016\/j.ejphar.2022.175048","journal-title":"Eur J Pharmacol"},{"key":"9533_CR40","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1039\/c9np00061e","volume":"37","author":"DD Zhang","year":"2020","unstructured":"Zhang DD, Chapman E (2020) The role of natural products in revealing Nrf2 function. Nat Prod Rep 37:797\u2013826. https:\/\/doi.org\/10.1039\/c9np00061e","journal-title":"Nat Prod Rep"},{"key":"9533_CR41","doi-asserted-by":"publisher","first-page":"120154","DOI":"10.1016\/j.lfs.2021.120154","volume":"288","author":"AA Azouz","year":"2022","unstructured":"Azouz AA, Omar HA, Hersi F, Ali FEM, Hussein Elkelawy AMM (2022) Impact of the ACE2 activator xanthenone on tacrolimus nephrotoxicity: modulation of uric acid\/ERK\/p38 MAPK and Nrf2\/SOD3\/GCLC signaling pathways. Life Sci 288:120154. https:\/\/doi.org\/10.1016\/j.lfs.2021.120154","journal-title":"Life Sci"},{"issue":"10","key":"9533_CR42","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1139\/cjpp-2020-0547","volume":"99","author":"SA Ibrahim","year":"2021","unstructured":"Ibrahim SA, Eltahawy NF, Abdalla AM, Khalaf HM (2021) Protective effects of selenium in tacrolimus-induced lung toxicity: potential role of heme oxygenase1. Can J Physiol Pharmacol 99(10):1069\u20131078. https:\/\/doi.org\/10.1139\/cjpp-2020-0547","journal-title":"Can J Physiol Pharmacol"},{"issue":"1","key":"9533_CR43","doi-asserted-by":"publisher","first-page":"5775","DOI":"10.1038\/s41598-020-62579-7","volume":"10","author":"A Mima","year":"2020","unstructured":"Mima A, Yasuzawa T, Nakamura T, Ueshima S (2020) Linagliptin affects IRS1\/Akt signaling and prevents high glucose-induced apoptosis in podocytes. Sci Rep 10(1):5775. https:\/\/doi.org\/10.1038\/s41598-020-62579-7","journal-title":"Sci Rep"},{"issue":"7","key":"9533_CR44","doi-asserted-by":"publisher","first-page":"e0200249","DOI":"10.1371\/journal.pone.0200249","volume":"13","author":"NY Spencer","year":"2018","unstructured":"Spencer NY, Yang Z, Sullivan JC, Klein T, Stanton RC (2018) Linagliptin unmasks specific antioxidant pathways protective against albuminuria and kidney hypertrophy in a mouse model of diabetes. PLoS ONE 13(7):e0200249. https:\/\/doi.org\/10.1371\/journal.pone.0200249","journal-title":"PLoS ONE"},{"issue":"7","key":"9533_CR45","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1007\/s11255-020-02474-2","volume":"52","author":"X Wei","year":"2020","unstructured":"Wei X, Zhu X, Jiang L, Huang X, Zhang Y, Zhao D, Du Y (2020) Recent advances in understanding the role of hypoxia-inducible factor 1\u03b1 in renal fibrosis. Int Urol Nephrol 52(7):1287\u20131295. https:\/\/doi.org\/10.1007\/s11255-020-02474-2","journal-title":"Int Urol Nephrol"},{"issue":"3","key":"9533_CR46","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/ndt\/gfac237","volume":"38","author":"N Knops","year":"2023","unstructured":"Knops N, Ramazani Y, De Loor H, Goldschmeding R, Nguyen TQ, van den Heuvel LP, Levtchenko E, Kuypers DJ (2023) Tacrolimus induces a pro-fibrotic response in donor-derived human proximal tubule cells dependent on common variants of the CYP3A5 and ABCB1 genes. Nephrol Dial Transpl 38(3):599\u2013609. https:\/\/doi.org\/10.1093\/ndt\/gfac237","journal-title":"Nephrol Dial Transpl"},{"issue":"3","key":"9533_CR47","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/cns.13042","volume":"25","author":"DH Mi","year":"2019","unstructured":"Mi DH, Fang HJ, Zheng GH, Liang XH, Ding YR, Liu X, Liu LP (2019) DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic\/high-glucose conditions, potentially through the SIRT1\/HIF-1\/VEGF pathway. CNS Neurosci Ther 25(3):323\u2013332. https:\/\/doi.org\/10.1111\/cns.13042","journal-title":"CNS Neurosci Ther"},{"key":"9533_CR48","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1475-2840-12-125","volume":"12","author":"Y Ishibashi","year":"2013","unstructured":"Ishibashi Y, Matsui T, Maeda S, Higashimoto Y, Yamagishi S (2013) Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate\/insulin-like growth factor II receptor. Cardiovasc Diabetol 12:125. https:\/\/doi.org\/10.1186\/1475-2840-12-125","journal-title":"Cardiovasc Diabetol"},{"issue":"10","key":"9533_CR49","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1111\/ajt.14316","volume":"17","author":"J Jin","year":"2017","unstructured":"Jin J, Jin L, Luo K, Lim SW, Chung BH, Yang CW (2017) Effect of empagliflozin on tacrolimus-induced pancreas islet dysfunction and renal injury. Am J Transpl 17(10):2601\u20132616. https:\/\/doi.org\/10.1111\/ajt.14316","journal-title":"Am J Transpl"},{"issue":"8","key":"9533_CR50","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.3390\/ijms21082987","volume":"21","author":"AI Korbut","year":"2020","unstructured":"Korbut AI, Taskaeva IS, Bgatova NP, Muraleva NA, Orlov NB, Dashkin MV, Khotskina AS, Zavyalov EL, Konenkov VI, Klein T, Klimontov VV (2020) SGLT2 inhibitor Empagliflozin and DPP4 inhibitor linagliptin reactivate glomerular autophagy in db\/db mice, a model of type 2 diabetes. Int J Mol Sci 21(8):2987. https:\/\/doi.org\/10.3390\/ijms21082987","journal-title":"Int J Mol Sci"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-024-09533-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-024-09533-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-024-09533-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T03:05:36Z","timestamp":1738724736000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-024-09533-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,5]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["9533"],"URL":"https:\/\/doi.org\/10.1007\/s11033-024-09533-2","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,5]]},"assertion":[{"value":"11 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were conducted under the approval of the Institutional Animal Ethics Committee (IAEC) of the Faculty of Pharmacy, Al-Azhar University, with the reference number \u201cAzhar-Pharmacy-2020-001\u201d, and strictly followed the ethical guidelines of The Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"608"}}