{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T17:27:01Z","timestamp":1769880421288,"version":"3.49.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lebanese American University President Intramural Research Fund","award":["I0005"],"award-info":[{"award-number":["I0005"]}]},{"name":"Lebanese American University President Intramural Research Fund","award":["I0030"],"award-info":[{"award-number":["I0030"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Renal fibrosis is a major manifestation of chronic kidney disease. To date, there are no treatments to reverse kidney fibrosis. Cannabis is an aromatic herb that is widely known for its anti-diabetic and anti-inflammatory properties. The aim of this study is to evaluate the protective effect of Lebanese cannabis oil extract (COE) against folic acid (FA) induced renal injury both in vitro and in vivo.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>A single dose of 250 mg\/kg of Folic acid was administered to induce renal fibrosis in rats. COE was injected at varying doses of 5, 10, and 20 mg\/kg. Body weight of rats were monitored and clinical parameters including serum creatinine, urea, and electrolytes were measured. Moreover, pathological examination of the kidney and heart was performed. Conditionally immortalized cultured rat podocytes were exposed to high concentrations of folic acid in the presence or absence of COE. MTS and in vitro scratch assay were used to assess podocyte cells viability and migration respectively. Western blot analysis was used to evaluate the phosphorylation levels of AKT and p38 MAPK.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Rats that received FA showed a marked increase in serum creatinine when compared to the non-treated control group. COE at doses of 5 and 10 mg\/kg significantly decreased serum creatinine induced by FA. Serum sodium was significantly reduced in all the groups receiving COE. Furthermore, COE ameliorated renal and cardiac pathology abnormalities caused by FA in a dose-dependent manner. Cell viability assay revealed that COE reversed cytotoxicity induced by FA in rat podocytes. In vitro scratch assay showed that COE partially restored the migratory capacity of podocytes incubated with FA. Dose-dependent experiments showed that COE (1 and 2\u03bcg\/ml) induced a significant increase of phospho-(S473)-AKT along with a decrease in phospho (T180 + Y182) P38 levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The current results revealed important protective effect of Lebanese cannabis oil extract against folic acid\u2014induced renal fibrosis in rats.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0311790","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T18:30:29Z","timestamp":1734028229000},"page":"e0311790","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lebanese cannabis oil extract protected against folic acid-induced kidney fibrosis in rats"],"prefix":"10.1371","volume":"19","author":[{"given":"Diana","family":"Bylan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alia","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wassim","family":"Shebaby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christabel","family":"Habchy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selim","family":"Nasser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-3687","authenticated-orcid":true,"given":"Wissam H.","family":"Faour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1572-7133","authenticated-orcid":true,"given":"Mohamad","family":"Mroueh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"issue":"3","key":"pone.0311790.ref001","doi-asserted-by":"crossref","first-page":"e342","DOI":"10.1016\/S2214-109X(24)00050-0","article-title":"The major global burden of chronic kidney disease","volume":"12","author":"M Jadoul","year":"2024","journal-title":"The Lancet Global health"},{"issue":"12","key":"pone.0311790.ref002","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/ki.2011.368","article-title":"The contribution of chronic kidney disease to the global burden of major noncommunicable diseases","volume":"80","author":"WG Couser","year":"2011","journal-title":"Kidney international"},{"issue":"9","key":"pone.0311790.ref003","first-page":"e1308","article-title":"Global Dialysis Perspective Lebanon","volume":"4","author":"M Aoun","year":"2023"},{"issue":"1","key":"pone.0311790.ref004","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1186\/s12913-022-07936-0","article-title":"Cost of illness of chronic kidney disease in Lebanon: from the societal and third-party payer perspectives.","volume":"22","author":"M Aoun","year":"2022","journal-title":"BMC health services research."},{"issue":"7","key":"pone.0311790.ref005","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3345\/kjp.2010.53.7.735","article-title":"Renal fibrosis.","volume":"53","author":"MH Cho","year":"2010","journal-title":"Korean journal of pediatrics"},{"issue":"1","key":"pone.0311790.ref006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21873\/invivo.11019","article-title":"Pathophysiological Mechanisms of Renal Fibrosis: A Review of Animal Models and Therapeutic Strategies","volume":"31","author":"A Nogueira","year":"2017","journal-title":"In vivo"},{"issue":"1","key":"pone.0311790.ref007","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41572-020-0196-7","article-title":"Podocytopathies.","volume":"6","author":"JB Kopp","year":"2020","journal-title":"Nature reviews Disease primers"},{"issue":"8","key":"pone.0311790.ref008","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.ekir.2020.05.024","article-title":"Assessing the Impact of Losmapimod on Proteinuria in Idiopathic Focal Segmental Glomerulosclerosis","volume":"5","author":"DS Gipson","year":"2020","journal-title":"Kidney international reports"},{"issue":"9","key":"pone.0311790.ref009","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1681\/ASN.2004121084","article-title":"Role of p38 mitogen-activated protein kinase activation in podocyte injury and proteinuria in experimental nephrotic syndrome. 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