Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics
Cyclophosphamide, an alkylating agent integral to specific cancer chemotherapy protocols, is often curtailed in application owing to its significant hepatotoxic side effects. Therefore, this study was conducted to assess the hepatoprotective potential of sesamin, a plant-originated antioxidant, usin...
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MDPI AG
2023-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/12/3238 |
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| author | Abdulmajeed M. Jali Mohammad Firoz Alam Ali Hanbashi Wedad Mawkili Basher M. Abdlasaed Saeed Alshahrani Abdullah M. Qahl Ahmad S. S. Alrashah Hamad Al Shahi |
| author_facet | Abdulmajeed M. Jali Mohammad Firoz Alam Ali Hanbashi Wedad Mawkili Basher M. Abdlasaed Saeed Alshahrani Abdullah M. Qahl Ahmad S. S. Alrashah Hamad Al Shahi |
| author_sort | Abdulmajeed M. Jali |
| collection | DOAJ |
| description | Cyclophosphamide, an alkylating agent integral to specific cancer chemotherapy protocols, is often curtailed in application owing to its significant hepatotoxic side effects. Therefore, this study was conducted to assess the hepatoprotective potential of sesamin, a plant-originated antioxidant, using rat models. The rats were divided into five groups: a control group received only the vehicle for six days; a cyclophosphamide group received an intraperitoneal (i.p.) single injection of cyclophosphamide (150 mg/kg) on day four; a sesamin group received a daily high oral dose (20 mg/kg) of sesamin for six days; and two groups were pretreated with oral sesamin (10 and 20 mg/kg daily from day one to day six) followed by an i.p. injection of cyclophosphamide on day four. The final and last sesamin dose was administered 24 h before euthanasia. At the end of the experiment, blood and liver tissue were collected for biochemical and histopathological assessments. The results indicated significantly increased liver markers (AST, ALT, ALP, and BIL), cytokines (TNFα and IL-1β), caspase-3, and malondialdehyde (MDA) in the cyclophosphamide group as compared to the normal control. Additionally, there was a significant decline in antioxidants (GSH) and antioxidant enzymes (CAT and SOD), but the sesamin treatment reduced liver marker enzymes, cytokines, and caspase-3 and improved antioxidants and antioxidant enzymes. Thus, sesamin effectively countered these alterations and helped to normalize the histopathological alterations. In conclusion, sesamin demonstrated the potential for attenuating cyclophosphamide-induced hepatotoxicity by modulating cytokine networks, apoptotic pathways, and oxidative stress, suggesting its potential role as an adjunct in chemotherapy to reduce hepatotoxicity. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T20:58:48Z |
| publishDate | 2023-12-01 |
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| series | Biomedicines |
| spelling | doaj.art-95e156421f5d4e5a93d2cae9df9094cb2023-12-22T13:55:03ZengMDPI AGBiomedicines2227-90592023-12-011112323810.3390/biomedicines11123238Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological CharacteristicsAbdulmajeed M. Jali0Mohammad Firoz Alam1Ali Hanbashi2Wedad Mawkili3Basher M. Abdlasaed4Saeed Alshahrani5Abdullah M. Qahl6Ahmad S. S. Alrashah7Hamad Al Shahi8Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Biology, Faculty of Education, Alasmaray Islamic University, Zliten 218521, LibyaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaCyclophosphamide, an alkylating agent integral to specific cancer chemotherapy protocols, is often curtailed in application owing to its significant hepatotoxic side effects. Therefore, this study was conducted to assess the hepatoprotective potential of sesamin, a plant-originated antioxidant, using rat models. The rats were divided into five groups: a control group received only the vehicle for six days; a cyclophosphamide group received an intraperitoneal (i.p.) single injection of cyclophosphamide (150 mg/kg) on day four; a sesamin group received a daily high oral dose (20 mg/kg) of sesamin for six days; and two groups were pretreated with oral sesamin (10 and 20 mg/kg daily from day one to day six) followed by an i.p. injection of cyclophosphamide on day four. The final and last sesamin dose was administered 24 h before euthanasia. At the end of the experiment, blood and liver tissue were collected for biochemical and histopathological assessments. The results indicated significantly increased liver markers (AST, ALT, ALP, and BIL), cytokines (TNFα and IL-1β), caspase-3, and malondialdehyde (MDA) in the cyclophosphamide group as compared to the normal control. Additionally, there was a significant decline in antioxidants (GSH) and antioxidant enzymes (CAT and SOD), but the sesamin treatment reduced liver marker enzymes, cytokines, and caspase-3 and improved antioxidants and antioxidant enzymes. Thus, sesamin effectively countered these alterations and helped to normalize the histopathological alterations. In conclusion, sesamin demonstrated the potential for attenuating cyclophosphamide-induced hepatotoxicity by modulating cytokine networks, apoptotic pathways, and oxidative stress, suggesting its potential role as an adjunct in chemotherapy to reduce hepatotoxicity.https://www.mdpi.com/2227-9059/11/12/3238sesamincyclophosphamidehepatoprotectivehepatotoxicityhistopathologycytokines |
| spellingShingle | Abdulmajeed M. Jali Mohammad Firoz Alam Ali Hanbashi Wedad Mawkili Basher M. Abdlasaed Saeed Alshahrani Abdullah M. Qahl Ahmad S. S. Alrashah Hamad Al Shahi Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics Biomedicines sesamin cyclophosphamide hepatoprotective hepatotoxicity histopathology cytokines |
| title | Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics |
| title_full | Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics |
| title_fullStr | Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics |
| title_full_unstemmed | Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics |
| title_short | Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics |
| title_sort | sesamin s therapeutic actions on cyclophosphamide induced hepatotoxicity molecular mechanisms and histopathological characteristics |
| topic | sesamin cyclophosphamide hepatoprotective hepatotoxicity histopathology cytokines |
| url | https://www.mdpi.com/2227-9059/11/12/3238 |
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