Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment
Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local infla...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2022-04-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/27/4/10.31083/j.fbl2704114 |
| _version_ | 1817988842271014912 |
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| author | Marta Banaszkiewicz Paulina Tarwacka Anna Krzywonos-Zawadzka Agnieszka Olejnik Robert Laprairie Agnieszka Noszczyk-Nowak Grzegorz Sawicki Iwona Bil-Lula |
| author_facet | Marta Banaszkiewicz Paulina Tarwacka Anna Krzywonos-Zawadzka Agnieszka Olejnik Robert Laprairie Agnieszka Noszczyk-Nowak Grzegorz Sawicki Iwona Bil-Lula |
| author_sort | Marta Banaszkiewicz |
| collection | DOAJ |
| description | Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (Δ9-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if Δ9-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury. Methods: Two experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent ex vivo/chemical in vitro I/R protocol with/without Δ9-THC treatment. The following parameters were measured: cell metabolic activity, morphology changes, cell damage as lactate dehydrogenase (LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant capacity (TAC) and heart hemodynamic parameters. Results: Δ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (p < 0.05, N = 3–6). Cells subjected to I/R showed lower cytoplasmic LDH activity, and 10 μM Δ9-THC treatment reduced cell injury and increased LDH content (p = 0.019, N = 6–9). Morphology changes of HCM-spherical shape, vacuolisation of cytoplasm and swollen mitochondria—were inhibited due to Δ9-THC treatment. I/R condition affected cell viability, but 10 μM Δ9-THC decreased the number of dead cells (p = 0.005, N = 6–9). The total level of CERK was lower in the I/R group, reflecting oxidative/nitrosative stress changes. The administration of Δ9-THC effectively increased the production of CERK to the level of aerobic control (p = 0.028, N = 6–9). ROS level was significantly decreased in I/R cells (p = 0.007, N = 6–8), confirming oxidative stress, while administration of 10 μM Δ9-THC enhanced TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6–8). Conclusions: Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol. |
| first_indexed | 2024-04-14T00:39:27Z |
| format | Article |
| id | doaj.art-4d0080e3a4e048a3b9d0c5d0bb7c84f0 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-14T00:39:27Z |
| publishDate | 2022-04-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-4d0080e3a4e048a3b9d0c5d0bb7c84f02022-12-22T02:22:14ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-04-0127411410.31083/j.fbl2704114S2768-6701(22)00453-1Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future TreatmentMarta Banaszkiewicz0Paulina Tarwacka1Anna Krzywonos-Zawadzka2Agnieszka Olejnik3Robert Laprairie4Agnieszka Noszczyk-Nowak5Grzegorz Sawicki6Iwona Bil-Lula7Division of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, 50-556 Wroclaw, PolandDivision of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, 50-556 Wroclaw, PolandDivision of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, 50-556 Wroclaw, PolandDivision of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, 50-556 Wroclaw, PolandDrug Discovery and Development, College of Pharmacy and Nutrition, University of Saskatchewan, SK S7N 5E5, CanadaDepartment of Internal and Diseases with Clinic for Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-366 Wroclaw, PolandDivision of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, 50-556 Wroclaw, PolandDivision of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, 50-556 Wroclaw, PolandBackground: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (Δ9-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if Δ9-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury. Methods: Two experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent ex vivo/chemical in vitro I/R protocol with/without Δ9-THC treatment. The following parameters were measured: cell metabolic activity, morphology changes, cell damage as lactate dehydrogenase (LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant capacity (TAC) and heart hemodynamic parameters. Results: Δ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (p < 0.05, N = 3–6). Cells subjected to I/R showed lower cytoplasmic LDH activity, and 10 μM Δ9-THC treatment reduced cell injury and increased LDH content (p = 0.019, N = 6–9). Morphology changes of HCM-spherical shape, vacuolisation of cytoplasm and swollen mitochondria—were inhibited due to Δ9-THC treatment. I/R condition affected cell viability, but 10 μM Δ9-THC decreased the number of dead cells (p = 0.005, N = 6–9). The total level of CERK was lower in the I/R group, reflecting oxidative/nitrosative stress changes. The administration of Δ9-THC effectively increased the production of CERK to the level of aerobic control (p = 0.028, N = 6–9). ROS level was significantly decreased in I/R cells (p = 0.007, N = 6–8), confirming oxidative stress, while administration of 10 μM Δ9-THC enhanced TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6–8). Conclusions: Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol.https://www.imrpress.com/journal/FBL/27/4/10.31083/j.fbl2704114ischemia-reperfusion injurycardioprotection9-tetrahydrocannabinoloxidantsantioxidantsmatrix metalloproteinasescontractilityinflammation |
| spellingShingle | Marta Banaszkiewicz Paulina Tarwacka Anna Krzywonos-Zawadzka Agnieszka Olejnik Robert Laprairie Agnieszka Noszczyk-Nowak Grzegorz Sawicki Iwona Bil-Lula Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment Frontiers in Bioscience-Landmark ischemia-reperfusion injury cardioprotection 9-tetrahydrocannabinol oxidants antioxidants matrix metalloproteinases contractility inflammation |
| title | Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment |
| title_full | Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment |
| title_fullStr | Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment |
| title_full_unstemmed | Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment |
| title_short | Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment |
| title_sort | δ9 tetrahydrocannabinol δ9 thc improves ischemia reperfusion heart dysfunction and might serve as a cardioprotective agent in the future treatment |
| topic | ischemia-reperfusion injury cardioprotection 9-tetrahydrocannabinol oxidants antioxidants matrix metalloproteinases contractility inflammation |
| url | https://www.imrpress.com/journal/FBL/27/4/10.31083/j.fbl2704114 |
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