{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:08:20Z","timestamp":1788480500385,"version":"build-2803163510"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8L1411"],"award-info":[{"award-number":["CMRPG8L1411"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Histol"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1007\/s10735-024-10233-1","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:03:04Z","timestamp":1724749384000},"page":"803-823","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["SGLT2 inhibitor downregulated oxidative stress via activating AMPK pathway for cardiorenal (CR) protection in CR syndrome rodent fed with high protein diet"],"prefix":"10.1007","volume":"55","author":[{"given":"Chih-Chao","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben-Chung","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuen-Wei","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Y.","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanna","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hon-Kan","family":"Yip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"10233_CR1","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1161\/CIRCULATIONAHA.106.626929","volume":"115","author":"HE Cingolani","year":"2007","unstructured":"Cingolani HE, Ennis IL (2007) Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy. Circulation 115:1090\u20131100. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.106.626929","journal-title":"Circulation"},{"key":"10233_CR2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.64.s87.5.x","author":"AJ Collins","year":"2003","unstructured":"Collins AJ, Li S, Gilbertson DT, Liu J, Chen SC, Herzog CA (2003) Chronic kidney disease and cardiovascular disease in the Medicare population. Kidney Int Suppl. https:\/\/doi.org\/10.1046\/j.1523-1755.64.s87.5.x. S24-31","journal-title":"Kidney Int Suppl"},{"key":"10233_CR3","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1001\/jama.2009.1488","volume":"302","author":"DJ de Jager","year":"2009","unstructured":"de Jager DJ, Grootendorst DC, Jager KJ, van Dijk PC, Tomas LM, Ansell D, Collart F, Finne P, Heaf JG, De Meester J, Wetzels JF, Rosendaal FR, Dekker FW (2009) Cardiovascular and noncardiovascular mortality among patients starting dialysis. JAMA 302:1782\u20131789. https:\/\/doi.org\/10.1001\/jama.2009.1488","journal-title":"JAMA"},{"key":"10233_CR4","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1681\/ASN.2015040369","volume":"27","author":"L Garneata","year":"2016","unstructured":"Garneata L, Stancu A, Dragomir D, Stefan G, Mircescu G (2016) Ketoanalogue-supplemented vegetarian very low-protein Diet and CKD progression. J Am Soc Nephrol 27:2164\u20132176. https:\/\/doi.org\/10.1681\/ASN.2015040369","journal-title":"J Am Soc Nephrol"},{"key":"10233_CR5","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nrneph.2016.163","volume":"13","author":"RJ Glassock","year":"2017","unstructured":"Glassock RJ, Warnock DG, Delanaye P (2017) The global burden of chronic kidney disease: estimates, variability and pitfalls. Nat Rev Nephrol 13:104\u2013114. https:\/\/doi.org\/10.1038\/nrneph.2016.163","journal-title":"Nat Rev Nephrol"},{"key":"10233_CR6","doi-asserted-by":"publisher","first-page":"CD001892","DOI":"10.1002\/14651858.CD001892.pub5","volume":"10","author":"D Hahn","year":"2020","unstructured":"Hahn D, Hodson EM, Fouque D (2020) Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst Rev 10:CD001892. https:\/\/doi.org\/10.1002\/14651858.CD001892.pub5","journal-title":"Cochrane Database Syst Rev"},{"key":"10233_CR7","doi-asserted-by":"publisher","unstructured":"Huang TH, Chen YT, Sung PH, Chiang HJ, Chen YL, Chai HT, Chung SY, Tsai TH, Yang CC, Chen CH, Chen YL, Chang HW, Sun CK, Yip HK (2015) Peripheral blood-derived endothelial progenitor cell therapy prevented deterioration of chronic kidney disease in rats. Am J Transl Res 7:804\u2009\u2013\u200924. https:\/\/doi.org\/10.1111\/jcmm.15303","DOI":"10.1111\/jcmm.15303"},{"key":"10233_CR8","doi-asserted-by":"publisher","first-page":"8379","DOI":"10.1111\/jcmm.15303","volume":"24","author":"TH Huang","year":"2020","unstructured":"Huang TH, Yip HK, Sun CK, Chen YL, Yang CC, Lee FY (2020) P-cresyl sulfate causes mitochondrial hyperfusion in H9C2 cardiomyoblasts. J Cell Mol Med 24:8379\u20138390. https:\/\/doi.org\/10.1111\/jcmm.15303","journal-title":"J Cell Mol Med"},{"key":"10233_CR9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1440-1797.2010.01304.x","volume":"2","author":"SJ Hwang","year":"2010","unstructured":"Hwang SJ, Tsai JC, Chen HC (2010) Epidemiology, impact and preventive care of chronic kidney disease in Taiwan. Nephrol (Carlton) 15 Suppl 2:3\u20139. https:\/\/doi.org\/10.1111\/j.1440-1797.2010.01304.x","journal-title":"Nephrol (Carlton) 15 Suppl"},{"key":"10233_CR10","doi-asserted-by":"publisher","first-page":"e016270","DOI":"10.1161\/JAHA.120.016270","volume":"9","author":"M Packer","year":"2020","unstructured":"Packer M (2020) Molecular, Cellular, and clinical evidence that sodium-glucose cotransporter 2 inhibitors Act as Neurohormonal antagonists when used for the treatment of Chronic Heart failure. J Am Heart Assoc 9:e016270. https:\/\/doi.org\/10.1161\/JAHA.120.016270","journal-title":"J Am Heart Assoc"},{"key":"10233_CR11","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/s0008-6363(02)00735-6","volume":"57","author":"SM Pogwizd","year":"2003","unstructured":"Pogwizd SM, Sipido KR, Verdonck F, Bers DM (2003) Intracellular na in animal models of hypertrophy and heart failure: contractile function and arrhythmogenesis. Cardiovasc Res 57:887\u2013896. https:\/\/doi.org\/10.1016\/s0008-6363(02)00735-6","journal-title":"Cardiovasc Res"},{"key":"10233_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.celrep.2017.09.026","volume":"21","author":"RC Rabinovitch","year":"2017","unstructured":"Rabinovitch RC, Samborska B, Faubert B, Ma EH, Gravel SP, Andrzejewski S, Raissi TC, Pause A, St-Pierre J, Jones RG (2017) AMPK Maintains Cellular Metabolic Homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep 21:1\u20139. https:\/\/doi.org\/10.1016\/j.celrep.2017.09.026","journal-title":"Cell Rep"},{"key":"10233_CR13","doi-asserted-by":"publisher","unstructured":"Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, Lerma EV, Mezue K, Molitch M, Mullens W, Ronco C, Tang WHW, McCullough PA, Council on Clinical C (2019) American Heart Association Council on the Kidney in Cardiovascular D, and Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation 139:e840-e78. https:\/\/doi.org\/10.1161\/CIR.0000000000000664","DOI":"10.1161\/CIR.0000000000000664"},{"key":"10233_CR14","doi-asserted-by":"publisher","unstructured":"Scheen AJ (2014) Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet 53. https:\/\/doi.org\/10.1007\/s40262-013-0126-x. :213\u2009\u2013\u200925","DOI":"10.1007\/s40262-013-0126-x"},{"key":"10233_CR15","doi-asserted-by":"publisher","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","volume":"24","author":"M Schieber","year":"2014","unstructured":"Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453\u2013R462. https:\/\/doi.org\/10.1016\/j.cub.2014.03.034","journal-title":"Curr Biol"},{"key":"10233_CR16","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12933-019-0964-4","volume":"18","author":"Q Shao","year":"2019","unstructured":"Shao Q, Meng L, Lee S, Tse G, Gong M, Zhang Z, Zhao J, Zhao Y, Li G, Liu T (2019) Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet\/streptozotocin-induced diabetic rats. Cardiovasc Diabetol 18:165. https:\/\/doi.org\/10.1186\/s12933-019-0964-4","journal-title":"Cardiovasc Diabetol"},{"key":"10233_CR17","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.2337\/db19-0991","volume":"69","author":"X Sun","year":"2020","unstructured":"Sun X, Han F, Lu Q, Li X, Ren D, Zhang J, Han Y, Xiang YK, Li J (2020) Empagliflozin ameliorates obesity-related Cardiac Dysfunction by regulating Sestrin2-Mediated AMPK-mTOR Signaling and Redox Homeostasis in High-Fat Diet-Induced obese mice. Diabetes 69:1292\u20131305. https:\/\/doi.org\/10.2337\/db19-0991","journal-title":"Diabetes"},{"key":"10233_CR18","doi-asserted-by":"publisher","first-page":"112745","DOI":"10.1016\/j.biopha.2022.112745","volume":"148","author":"PH Sung","year":"2022","unstructured":"Sung PH, Chai HT, Yang CC, Chiang JY, Chen CH, Chen YL, Yip HK (2022a) Combined levosimendan and Sacubitril\/Valsartan markedly protected the heart and kidney against cardiorenal syndrome in rat. Biomed Pharmacother 148:112745. https:\/\/doi.org\/10.1016\/j.biopha.2022.112745","journal-title":"Biomed Pharmacother"},{"key":"10233_CR19","doi-asserted-by":"crossref","unstructured":"Sung PH, Cheng BC, Hsu TW, Chiang JY, Chiang HJ, Chen YL, Yang CC, Yip HK (2022b) Oxidized-LDL deteriorated the renal residual function and Parenchyma in CKD rat through upregulating epithelial mesenchymal transition and extracellular matrix-mediated Tubulointerstitial Fibrosis-Pharmacomodulation of Rosuvastatin. Antioxidants (Basel) 1110.3390\/antiox11122465","DOI":"10.3390\/antiox11122465"},{"key":"10233_CR20","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1002\/phar.1903","volume":"37","author":"JM Trujillo","year":"2017","unstructured":"Trujillo JM, Nuffer WA (2017) Impact of sodium-glucose cotransporter 2 inhibitors on nonglycemic outcomes in patients with type 2 diabetes. Pharmacotherapy 37:481\u2013491. https:\/\/doi.org\/10.1002\/phar.1903","journal-title":"Pharmacotherapy"},{"key":"10233_CR21","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1097\/MNH.0000000000000099","volume":"24","author":"K Tsuruya","year":"2015","unstructured":"Tsuruya K, Eriguchi M (2015) Cardiorenal syndrome in chronic kidney disease. Curr Opin Nephrol Hypertens 24:154\u2013162. https:\/\/doi.org\/10.1097\/MNH.0000000000000099","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"10233_CR22","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1007\/s00125-017-4509-7","volume":"61","author":"L Uthman","year":"2018","unstructured":"Uthman L, Baartscheer A, Bleijlevens B, Schumacher CA, Fiolet JWT, Koeman A, Jancev M, Hollmann MW, Weber NC, Coronel R, Zuurbier CJ (2018) Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of na(+)\/H(+) exchanger, lowering of cytosolic na(+) and vasodilation. Diabetologia 61:722\u2013726. https:\/\/doi.org\/10.1007\/s00125-017-4509-7","journal-title":"Diabetologia"},{"key":"10233_CR23","doi-asserted-by":"publisher","unstructured":"Virzi GM, Clementi A, de Cal M, Brocca A, Day S, Pastori S, Bolin C, Vescovo G, Ronco C (2015) Oxidative stress: dual pathway induction in cardiorenal syndrome type 1 pathogenesis. Oxid Med Cell Longev 2015:391790. https:\/\/doi.org\/10.1155\/2015\/391790","DOI":"10.1155\/2015\/391790"},{"key":"10233_CR24","doi-asserted-by":"publisher","first-page":"108954","DOI":"10.1016\/j.biopha.2019.108954","volume":"116","author":"CC Yang","year":"2019","unstructured":"Yang CC, Chen YT, Chen CH, Li YC, Shao PL, Huang TH, Chen YL, Sun CK, Yip HK (2019) The therapeutic impact of entresto on protecting against cardiorenal syndrome-associated renal damage in rats on high protein diet. Biomed Pharmacother 116:108954. https:\/\/doi.org\/10.1016\/j.biopha.2019.108954","journal-title":"Biomed Pharmacother"},{"key":"10233_CR25","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.biopha.2018.10.095","volume":"109","author":"CC Yang","year":"2019","unstructured":"Yang CC, Chen YT, Wallace CG, Chen KH, Cheng BC, Sung PH, Li YC, Ko SF, Chang HW, Yip HK (2019b) Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat. Biomed Pharmacother 109:658\u2013670. https:\/\/doi.org\/10.1016\/j.biopha.2018.10.095","journal-title":"Biomed Pharmacother"},{"key":"10233_CR26","doi-asserted-by":"publisher","first-page":"112244","DOI":"10.1016\/j.biopha.2021.112244","volume":"144","author":"JN Yeh","year":"2021","unstructured":"Yeh JN, Yue Y, Chu YC, Huang CR, Yang CC, Chiang JY, Yip HK, Guo J (2021) Entresto protected the cardiomyocytes and preserved heart function in cardiorenal syndrome rat fed with high-protein diet through regulating the oxidative stress and Mfn2-mediated mitochondrial functional integrity. Biomed Pharmacother 144:112244. https:\/\/doi.org\/10.1016\/j.biopha.2021.112244","journal-title":"Biomed Pharmacother"},{"key":"10233_CR27","unstructured":"Zhen YY, Yang CC, Hung CC, Lee CC, Lee CC, Wu CH, Chen YT, Chen WY, Chen KH, Yip HK, Ko SF (2017) Extendin-4 protects kidney from acute ischemia-reperfusion injury through upregulation of NRF2 signaling. Am J Transl Res 9:4756-71. https:\/\/doi.org\/"},{"key":"10233_CR28","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","volume":"373","author":"B Zinman","year":"2015","unstructured":"Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE, Investigators E-RO (2015) Empagliflozin, Cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117\u20132128. https:\/\/doi.org\/10.1056\/NEJMoa1504720","journal-title":"N Engl J Med"}],"container-title":["Journal of Molecular Histology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-024-10233-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-024-10233-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-024-10233-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T05:07:58Z","timestamp":1728450478000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10735-024-10233-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,27]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10233"],"URL":"https:\/\/doi.org\/10.1007\/s10735-024-10233-1","relation":{},"ISSN":["1567-2379","1567-2387"],"issn-type":[{"value":"1567-2379","type":"print"},{"value":"1567-2387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,27]]},"assertion":[{"value":"1 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 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":"Title of the approved project: To explore the molecular mechanism of SGLT2 inhibitor in modulating oxidative stress through AMPK pathway for cardiorenal protection in cardiorenal syndrome. Name of the institutional approval committee: All animal procedures were approved by the Institute of Animal Care and Use Committee (IACUC) at Kaohsiung Chang Gung Memorial Hospital. Approval number: Affidavit of Approval of Animal Use Protocol No. 2021062210. Date of approval: Jun. 22, 2021.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}