{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:18:57Z","timestamp":1791872337682,"version":"4.3.4"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rho kinase (ROCK) pathway plays a critical role in post\u2010COVID\u201019 pulmonary fibrosis (PCPF) and its intervention with angiotensin\u2010converting enzyme 2 (ACE2) and vascular endothelial growth factor (VEGF) will be a potential therapeutic target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The present study was conducted to investigate the efficacy of zoledronate (ZA) on carbon tetrachloride (CCl4) induced pulmonary fibrosis (PF) in rats through targeting ACE2, ROCK, and VEGF signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty male Wistar rats were divided into five groups: control, vehicle\u2010treated, PF, PF\u2010ZA 50, and PF\u2010ZA 100 groups. ZA was given in two different doses 100 and 50\u2009\u03bcg\/kg\/week intraperitoneally. After anesthesia, mean arterial blood pressure (MBP) was measured. After scarification, lung coefficient was calculated. Lung levels of ACE 2, interleukin\u20101\u03b2 (IL\u20101\u03b2), transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2), VEGF, glutathione (GSH), and superoxide dismutase (SOD) were measured. Expression of ROCK, phosphorylated myosin phosphatase target subunit 1 (P\u2010MYPT1), and matrix metalloproteinase (MMP\u20101), along with histopathological changes and immune\u2010histochemical staining for lung \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), tumor necrosis factor\u2010alpha (TNF\u03b1), and caspase\u20103, were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ZA significantly prevented the decrease in MBP. ZA significantly increased ACE2, GSH, and SOD and significantly decreased IL\u20101\u03b2, TGF\u2010\u03b2, and VEGF in lung in comparison to PF group. ZA prevented the histopathological changes induced by CCl4. ZA inhibited lung expression of ROCK, P\u2010MYPT1, MMP\u20101, \u03b1\u2010SMA, TNF\u03b1, and caspase\u20103 with significant differences favoring the high dose intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ZA in a dose\u2010dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.12994","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T10:00:30Z","timestamp":1707991230000},"page":"703-717","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post\u2010COVID\u201019 pulmonary fibrosis"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-2512","authenticated-orcid":false,"given":"Reham Hussein","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesma Hussein","family":"Abdel hay","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesma Mohamed","family":"Fawzy","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yomna M.","family":"Tamim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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