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To date, there has been no sufficient treatment for these cases, and further studies are highly recommended. Thus, our study aimed to evaluate the effect of sacubitril\/valsartan (SV) on testicular ischaemia\/reperfusion (TIR)\u2010induced testicular damage and remote cardiac effect in juvenile rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Forty juvenile Wistar albino rats were divided into five groups (<jats:italic>n<\/jats:italic>\u00a0=\u20098) as control; SV (60\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>); TIR\u2010induced group; TIR plus SV low\u2010dose (30\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>); TIR plus SV high\u2010dose (60\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>TIR induced testicular injury with remote cardiac effects, as we found a significant decrease in serum testosterone, increased cardiac enzyme levels and marked disturbances in oxidative stress parameters. Moreover, there are increases in angiotensin II (Ang II), neprilysin and apoptosis signal\u2010regulating kinase 1 (ASK1). In addition, there is a disturbance in phosphor\u2010nuclear factor kappa B (p\u2010NF\u2010\u03baB p65), tumour necrosis factor alpha (TNF\u03b1), Janus kinase 1 (JAK1), signal transducer and activator of transcription 4 (STAT4) and cleaved caspase 3 with abnormal histological features. However, SV co\u2010administration reversed damaging effect of TIR by regulating the renin angiotensin aldosterone system (RAAS), and anti\u2010inflammatory, anti\u2010oxidant, and anti\u2010apoptotic pharmacological and physiological properties, and by modulation of different pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>SV has protective properties against TIR\u2010induced damage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70092","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T21:29:46Z","timestamp":1748899786000},"page":"4343-4362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of sacubitril\/valsartan in testicular ischaemia reperfusion injury via modulation of AngII\/ASK\/NF\u2010\u03baB and JAK\/STAT pathways in juvenile rats"],"prefix":"10.1111","volume":"182","author":[{"given":"Marwa Monier Mahmoud","family":"Refaie","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Minia University  El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elshymaa A.","family":"Abdel\u2010Hakeem","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine Minia University  El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa","family":"Ahmed Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Histology and cell Biology Faculty of Medicine, Minia University  El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zamzam","family":"Hassan Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Minia University  El\u2010Minia 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