Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis

Abstract Background Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent. Objective The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis s...

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Main Authors: Alia Khalil, Sahar Al Toufaily, Wassim Shebaby, Marissa El Hage, Dima Mroue, Wissam Faour, Mohamad Mroueh
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Cannabis Research
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Online Access:https://doi.org/10.1186/s42238-025-00260-4
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author Alia Khalil
Sahar Al Toufaily
Wassim Shebaby
Marissa El Hage
Dima Mroue
Wissam Faour
Mohamad Mroueh
author_facet Alia Khalil
Sahar Al Toufaily
Wassim Shebaby
Marissa El Hage
Dima Mroue
Wissam Faour
Mohamad Mroueh
author_sort Alia Khalil
collection DOAJ
description Abstract Background Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent. Objective The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity. Methods Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured. Results Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone. Conclusion Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.
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spelling doaj-art-c4704924fe304c25a8f52ebb45dc92eb2025-01-19T12:37:41ZengBMCJournal of Cannabis Research2522-57822025-01-017111310.1186/s42238-025-00260-4Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosisAlia Khalil0Sahar Al Toufaily1Wassim Shebaby2Marissa El Hage3Dima Mroue4Wissam Faour5Mohamad Mroueh6Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American UniversitySchool of Pharmacy, Pharmaceutical Sciences Department, Lebanese American UniversitySchool of Pharmacy, Pharmaceutical Sciences Department, Lebanese American UniversitySchool of Pharmacy, Pharmaceutical Sciences Department, Lebanese American UniversityDepartment of Natural Sciences, School of Arts and Sciences, Lebanese American UniversityGilbert and Rose-Marie Chagoury School of Medicine, Lebanese American UniversitySchool of Pharmacy, Pharmaceutical Sciences Department, Lebanese American UniversityAbstract Background Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent. Objective The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity. Methods Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured. Results Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone. Conclusion Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.https://doi.org/10.1186/s42238-025-00260-4Cannabis sativaCisplatinNephrotoxicityPodocytesCisplatin-induced nephrotoxicity
spellingShingle Alia Khalil
Sahar Al Toufaily
Wassim Shebaby
Marissa El Hage
Dima Mroue
Wissam Faour
Mohamad Mroueh
Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis
Journal of Cannabis Research
Cannabis sativa
Cisplatin
Nephrotoxicity
Podocytes
Cisplatin-induced nephrotoxicity
title Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis
title_full Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis
title_fullStr Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis
title_full_unstemmed Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis
title_short Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis
title_sort lebanese cannabis sativa l extract protects from cisplatin induced nephrotoxicity in mice by inhibiting podocytes apoptosis
topic Cannabis sativa
Cisplatin
Nephrotoxicity
Podocytes
Cisplatin-induced nephrotoxicity
url https://doi.org/10.1186/s42238-025-00260-4
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