IMR Press / FBL / Volume 27 / Issue 4 / DOI: 10.31083/j.fbl2704114
Open Access Original Research
Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment
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1 Division 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, Poland
2 Drug Discovery and Development, College of Pharmacy and Nutrition, University of Saskatchewan, SK S7N 5E5, Canada
3 Department 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, Poland
4 Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, SK S7N 5E5, Canada
*Correspondence: iwona.bil‐ (Iwona Bil-Lula); (Grzegorz Sawicki)
These authors contributed equally.
Academic Editor: Josef Jampílek
Front. Biosci. (Landmark Ed) 2022, 27(4), 114;
Submitted: 13 December 2021 | Revised: 13 February 2022 | Accepted: 14 February 2022 | Published: 1 April 2022
(This article belongs to the Special Issue Myocardial Ischaemia–Reperfusion Injury)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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.

ischemia-reperfusion injury
matrix metalloproteinases
Fig. 1.
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