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Tadalafil (TAD), a phosphodiesterase-5 (PDE-5) inhibitor, has been observed to have a wide range of pharmacological actions, including nephroprotection. The study\u2019s objective was to examine the possible underlying protective mechanism of TAD against AmB-induced nephrotoxicity. Experimentally, animals were divided randomly into four groups: control, TAD (5 mg\/kg\/day; p.o.), AmB (18.5 mg\/kg\/day; i.p.), and TAD+AmB groups. Sera and tissue samples were processed for biochemical, molecular, and histological analyses. The biochemical investigations showed that TAD significantly ameliorated the increase of kidney function biomarkers (creatinine, urea, CysC, KIM-1) in serum, renal nitric oxide (NO), lipid peroxidation (MDA), and inflammatory cytokines (TNF-\u03b1, IL-6) in AmB-treated rats. Meanwhile, TAD significantly retarded AmB-induced decrease in serum magnesium, sodium, potassium, and renal glutathione content. Molecular analysis revealed that TAD reduced AmB-induced imbalance in the protein expression of eNOS\/iNOS, which explains its regulatory effect on renal NO content. These results were also supported by the down-regulation of nuclear NF-\u03baB p65 and cleaved caspase-3 protein expressions, as well as the improvement of histological features by TAD in AmB-treated rats. Therefore, it can be suggested that TAD could be a promising candidate for renoprotection against AmB-induced AKI. That could be partly attributed to its regulatory effect on renal eNOS\/iNOS balance and NO, the inhibition of NF-\u03baB p65 nuclear translocation, its downstream inflammatory cytokines and iNOS, and ultimately the inhibition of caspase-3-induced renal apoptosis.<\/jats:p>","DOI":"10.1007\/s00210-023-02787-w","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T23:24:00Z","timestamp":1698449040000},"page":"3141-3153","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Regulation of renal nitric oxide and eNOS\/iNOS expression by tadalafil participates in the mitigation of amphotericin B\u2013induced renal injury: Down-regulation of NF-\u03baB\/iNOS\/caspase-3 signaling"],"prefix":"10.1007","volume":"397","author":[{"given":"Doaa M.","family":"Abdel-Rahman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basim Anwar Shehata","family":"Messiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fares E.M.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany A.","family":"Azouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,28]]},"reference":[{"key":"2787_CR1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.5152\/akd.2015.15072","volume":"15","author":"Z Abassi","year":"2015","unstructured":"Abassi Z, Armaly Z (2015) Phosphodiesterase-5 inhibitors: emerging nephroprotective drugs. 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