{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:21:11Z","timestamp":1766553671027,"version":"3.48.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovations of the Republic of Serbia","award":["451\u201303\u2013136\/2025\u201303\/200007"],"award-info":[{"award-number":["451\u201303\u2013136\/2025\u201303\/200007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Chemical androgen deprivation and estrogenization are essential components of clinical treatment for advanced prostate cancer and male-to-female sex transition. The aim of this study was to determine the effects of these therapies on anthropometric parameters, liver histology, and biochemical parameters, with the goal of establishing experimental models that accurately represent current clinical practice. Materials and Methods: Young adult Wistar rats were divided into nine groups: intact control (IC), control vehicle (CV), cyproterone acetate-treated (CA), flutamide-treated (F), control sesame oil (CO), estradiol valerate-treated (E), combined control (CC), flutamide + estradiol valerate (F + E), and cyproterone acetate + estradiol valerate (CA + E)-treated groups. Treatments were administered by subcutaneous injection for four weeks. Results: The administration of estradiol valerate, alone or combined with antiandrogens, reduced final body mass and white adipose tissue mass. Notable changes were observed in absolute and relative pituitary, liver, prostate, and testis mass in the E, F + E and CA + E groups. There were no significant changes in liver histology or glycogen deposition; however, the combined treatment groups showed an increased volume density of binucleated hepatocytes and fibrotic tissue. Regarding biochemical parameters, androgen deprivation and\/or estrogenization caused marked changes in serum triglyceride, LDL (low-density lipoproteins), ALP (alkaline phosphatase), AST (aspartate aminotransferase), ALT (alanine aminotransferase), Bil-T (bilirubin), creatinine, and urea levels. Conclusions: Given the importance of these therapies in clinical practice, providing a model based on the evaluated parameters offers a solid platform for future research.<\/jats:p>","DOI":"10.3390\/medicina62010008","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:27:16Z","timestamp":1766154436000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Male Rat Model of Chemical Androgen Deprivation and Estrogenization from the Perspective of Anthropometric, Histological, and Biochemical Parameters"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0963-5167","authenticated-orcid":false,"given":"Pavle","family":"\u0106osi\u0107","sequence":"first","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4583-3281","authenticated-orcid":false,"given":"Milica","family":"Vukojevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-3138","authenticated-orcid":false,"given":"Marko","family":"Miler","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-763X","authenticated-orcid":false,"given":"Branko","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-8799","authenticated-orcid":false,"given":"Milica","family":"Manojlovi\u0107-Stojanoski","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-9603","authenticated-orcid":false,"given":"Vladimir","family":"Ajd\u017eanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41391-018-0079-0","article-title":"Androgen-targeted therapy in men with prostate cancer: Evolving practice and future considerations","volume":"22","author":"Crawford","year":"2018","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/ncpuro1296","article-title":"Androgen deprivation therapy: Progress in understanding mechanisms of resistance and optimizing androgen depletion","volume":"6","author":"Harris","year":"2009","journal-title":"Nat. Clin. Pract. Urol."},{"key":"ref_3","first-page":"97","article-title":"Endocrinology of Transgender Medicine","volume":"40","author":"Arcelus","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/S1470-2045(09)70229-3","article-title":"Anti-androgens and androgen-depleting therapies in prostate cancer: New agents for an established target","volume":"10","author":"Chen","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0094-0143(21)01398-7","article-title":"Use of Cyproterone Acetate in Prostate Cancer","volume":"18","author":"Goldenberg","year":"1991","journal-title":"Urol. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1300\/J485v09n03_06","article-title":"Physical Aspects of Transgender Endocrine Therapy","volume":"9","author":"Dahl","year":"2006","journal-title":"Int. J. Transgenderism"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jsbmb.2004.10.005","article-title":"Endocrine treatment of prostate cancer","volume":"92","author":"Tammela","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/j.jsxm.2016.09.001","article-title":"Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol","volume":"13","author":"Arnold","year":"2016","journal-title":"J. Sex. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1161\/HYPERTENSIONAHA.119.13080","article-title":"Gender-Affirming Hormone Therapy, Vascular Health and Cardiovascular Disease in Transgender Adults","volume":"74","author":"Connelly","year":"2019","journal-title":"Hypertension"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.eururo.2006.08.043","article-title":"Antiandrogens in the treatment of prostate cancer","volume":"51","author":"Wirth","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_11","first-page":"725","article-title":"Hormonal Gender Reassignment Treatment for Gender Dysphoria","volume":"117","author":"Meyer","year":"2020","journal-title":"Dtsch. \u00c4rztebl. Int."},{"key":"ref_12","first-page":"CD013138","article-title":"Antiandrogens or estradiol treatments or both during hormone replacement therapy in transitioning transgender women","volume":"2018","author":"Haupt","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/joim.13441","article-title":"Gender\u2014affirming hormone therapy: An updated literature review with an eye on the future","volume":"291","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_14","first-page":"1431","article-title":"The laboratory rat: Age and body weight matter","volume":"20","author":"Ghasemi","year":"2021","journal-title":"EXCLI J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1111\/j.1464-410X.2011.10127.x","article-title":"Androgen deprivation therapy in prostate cancer: Are rising concerns leading to falling use?","volume":"108","author":"Krahn","year":"2011","journal-title":"BJU Int."},{"key":"ref_16","first-page":"1257","article-title":"Daidzein effects on ACTH cells: Immunohistomorphometric and hormonal study in an animal model of the andropause","volume":"26","author":"Ajdzanovic","year":"2011","journal-title":"Histol. Histopathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151487","DOI":"10.1016\/j.aanat.2020.151487","article-title":"The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study","volume":"230","author":"Miler","year":"2020","journal-title":"Ann. Anat.-Anat. Anz."},{"key":"ref_18","first-page":"1377","article-title":"Structure and hormonal output of the adrenal gland after experimental estrogenization of male rats","volume":"40","author":"Miler","year":"2025","journal-title":"Histol. Histopathol."},{"key":"ref_19","first-page":"313","article-title":"The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis","volume":"222","year":"2012","journal-title":"Am. J. Anat."},{"key":"ref_20","first-page":"627","article-title":"Genistein stimulates the hypothalamo-pituitary-adrenal axis in adult rats: Morphological and hormonal study","volume":"27","year":"2012","journal-title":"Histol. Histopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.3181\/0703-BC-82","article-title":"Subcutaneously administrated genistein and daidzein decrease serum cholesterol and increase triglyceride levels in male middle-aged rats","volume":"232","author":"Stojanoski","year":"2007","journal-title":"Exp. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.acthis.2015.04.002","article-title":"Testosterone application decreases the capacity for ACTH and corticosterone secretion in a rat model of the andropause","volume":"117","author":"Miler","year":"2015","journal-title":"Acta Histochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1210\/jc.2009-0345","article-title":"Endocrine treatment of transsexual persons: An Endocrine Society clinical practice guideline","volume":"94","author":"Hembree","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.jsxm.2017.03.251","article-title":"Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents","volume":"14","author":"Tack","year":"2017","journal-title":"J. Sex. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1016\/S0022-5347(01)66670-9","article-title":"Estrogens in the treatment of prostate cancer","volume":"154","author":"Cox","year":"1995","journal-title":"J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"unstructured":"U.S. Food and Drug Administration (2005). Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers, FDA.","key":"ref_27"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"152322","DOI":"10.1016\/j.aanat.2024.152322","article-title":"Vitamin D3 application and factors of its activity in the adrenal cortex of andropausal rats: A functionally-histological study","volume":"256","author":"Miler","year":"2024","journal-title":"Ann. Anat.-Anat. Anz."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s11764-009-0114-1","article-title":"The effect of androgen deprivation therapy on body composition in men with prostate cancer: Systematic review and meta-analysis","volume":"4","author":"Haseen","year":"2010","journal-title":"J. Cancer Surviv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0303-7207(01)00414-2","article-title":"The role of estrogen and estrogen receptor-\u03b1 in male adipose tissue","volume":"178","author":"Cooke","year":"2001","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_31","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age with Human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1016\/j.juro.2009.01.047","article-title":"Metabolic complications of androgen deprivation therapy for prostate cancer","volume":"181","author":"Saylor","year":"2009","journal-title":"J. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11404","DOI":"10.1074\/jbc.275.15.11404","article-title":"Estrogen suppresses transcription of lipoprotein lipase gene: Existence of a unique estrogen response element on the lipoprotein lipase pro-moter","volume":"275","author":"Homma","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1210\/jc.2003-031327","article-title":"Estrogen Controls Lipolysis by Up-Regulating \u03b12A-Adrenergic Receptors Directly in Human Adipose Tissue through the Estrogen Receptor \u03b1. Implications for the Female Fat Distribution","volume":"89","author":"Pedersen","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jsbmb.2010.06.012","article-title":"Metabolic impact of estrogen signalling through ERalpha and ERbeta","volume":"122","author":"Kintscher","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"98","DOI":"10.4103\/aja202212","article-title":"Associations of sex hormone levels with body mass index (BMI) in men: A cross-sectional study using quantile regression analysis","volume":"25","author":"Lv","year":"2022","journal-title":"Asian J. Androl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"H866","DOI":"10.1152\/ajpheart.1990.259.3.H866","article-title":"Effects of sex hormones on development of physiological and pathological cardiac hypertrophy in male and female rats","volume":"259","author":"Malhotra","year":"1990","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S0735-1097(98)00347-7","article-title":"Hypertrophic remodeling: Gender differences in the early response to left ventricular pressure overload","volume":"32","author":"Douglas","year":"1998","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1194\/jlr.M028969","article-title":"Differential effects of estrogen\/androgen on the prevention of nonalcoholic fatty liver disease in the male rat","volume":"54","author":"Zhang","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_40","first-page":"691","article-title":"Characteristics of flutamide action on prostatic and testicular functions in the rat","volume":"29","author":"Marchetti","year":"1988","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_41","first-page":"e13482","article-title":"Protective effect of ethanolic extract of Hygrophila auriculata seeds in cyproterone acetate\u2014induced sexual dysfunction in male albino rats","volume":"52","author":"Ghosh","year":"2019","journal-title":"Andrologia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/jsm.12036","article-title":"Androgen Deprivation Therapy Impact on Quality of Life and Cardiovascular Health, Monitoring Therapeutic Replacement","volume":"10","author":"Trost","year":"2013","journal-title":"J. Sex. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1095\/biolreprod21.2.455","article-title":"Interactions of Testosterone and Estradiol-17\u03b2 on the Reproductive Tract of the Male Rat1","volume":"21","author":"Robaire","year":"1979","journal-title":"Biol. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39931","DOI":"10.1038\/srep39931","article-title":"Effects of Elevated \u03b2-Estradiol Levels on the Functional Morphology of the Testis\u2014New Insights","volume":"7","author":"Leavy","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0090-4295(82)90345-4","article-title":"Serum lipid changes after estrogen therapy in prostatic carcinoma","volume":"20","author":"Bulusu","year":"1982","journal-title":"Urology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1089\/lgbt.2023.0065","article-title":"Body Composition and Metabolic Syndrome Components in Transgender\/Gender Diverse Adolescents and Young Adults","volume":"11","author":"Borger","year":"2024","journal-title":"LGBT Health"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"19095","DOI":"10.1074\/jbc.M300982200","article-title":"Liver cell polyploidization: A pivotal role for binuclear hepatocytes","volume":"278","author":"Guidotti","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.drudis.2021.12.012","article-title":"Therapeutic potential of targeting regulatory mechanisms of hepatic stellate cell activation in liver fibrosis","volume":"27","author":"Baghaei","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/j.metabol.2009.05.010","article-title":"Sex steroids deficiency impairs glucose transporter 4 expression and its translocation through defective Akt phosphorylation in target tissues of adult male rat","volume":"58","author":"Muthusamy","year":"2009","journal-title":"Metabolism"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"156686","DOI":"10.1016\/j.cyto.2024.156686","article-title":"Protective effects of 17-\u03b2-estradiol on liver injury: The role of TLR4 signaling pathway and inflammatory response","volume":"181","author":"Khaksari","year":"2024","journal-title":"Cytokine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1055\/a-2211-2144","article-title":"The Ploidy State as a Determinant of Hepatocyte Proliferation","volume":"43","author":"Wilson","year":"2023","journal-title":"Semin. Liver Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.lfs.2003.08.004","article-title":"Antioxidant and antiapoptotic activities of idoxifene and estradiol in hepatic fibrosis in rats","volume":"74","author":"Lu","year":"2004","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1148\/radiology.199.2.8668793","article-title":"Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer","volume":"199","author":"Rosenthal","year":"1996","journal-title":"Radiology"},{"key":"ref_54","first-page":"678","article-title":"Flutamide-induced liver injury: A case report","volume":"61","author":"Chu","year":"1998","journal-title":"Zhonghua Yi Xue Za Zhi= Chin. Med. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/liv.12899","article-title":"Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid\u2014responsive hepatitis: Report of 22 cases","volume":"36","author":"Bessone","year":"2015","journal-title":"Liver Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.steroids.2007.12.026","article-title":"Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: Protective effect of 17\u03b2-estradiol","volume":"73","author":"Hamden","year":"2008","journal-title":"Steroids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.3233\/JAD-201241","article-title":"Low liver enzymes and risk of dementia: The atherosclerosis risk in communities (ARIC) study","volume":"79","author":"Lu","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.jsxm.2021.06.011","article-title":"Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy","volume":"18","author":"Hashemi","year":"2021","journal-title":"J. Sex. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1177\/1470320315595568","article-title":"Aldosterone effects on glomerular structure and function","volume":"16","author":"Bernardi","year":"2015","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/ajh.2012.21","article-title":"Flutamide increases aldosterone levels in gonadectomized male but not female wistar rats","volume":"25","author":"Hofmann","year":"2012","journal-title":"Am. J. Hypertens."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1161\/HYPERTENSIONAHA.107.105767","article-title":"Sex steroids and renal disease: Lessons from animal studies","volume":"51","author":"Yanes","year":"2008","journal-title":"Hypertension"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/00041552-200103000-00010","article-title":"Gender and the progression of renal disease","volume":"10","author":"Seliger","year":"2001","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0090-4295(75)90105-3","article-title":"Blood urea nitrogen and serum creatinine: Physiology and interpretations","volume":"5","author":"Baum","year":"1975","journal-title":"Urology"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/8\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:17:58Z","timestamp":1766553478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["medicina62010008"],"URL":"https:\/\/doi.org\/10.3390\/medicina62010008","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2025,12,19]]}}}