[Epub ahead of print]
Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.
Source
Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia. Electronic address: amrfouad65@yahoo.com.
Abstract
The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg-1i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg-1. Cannabidiol treatment (5mgkg-1/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks.Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.
Copyright © 2013 Elsevier B.V. All rights reserved.
Copyright © 2013 Elsevier B.V. All rights reserved.
- PMID:
23721741
[PubMed – as supplied by publisher]
Figures and tables from this article:
- Fig. 1. Photomicrographs of rat heart (H&E) from: (A, 200×) control group showing normal architecture of cardiac tissue; (B, 200× and C, 400×) doxorubicin group without cannabidiol treatment showing widespread damage in the form of cytoplasmic vacuolization, loss of muscle fibers, edema, hemorrhages (B, black arrow) and coagulative necrosis (C, white arrow); (D, 200×) doxorubicin plus cannabidiol group showing a histological picture comparable to that of the control group.
- Fig. 2. Immunohistochemical staining of inducible nitric oxide synthase (iNOS) in rat heart (200×) from: (A) control group showing no expression of iNOS; (B) doxorubicin group without cannabidiol treatment showing a significant increase in iNOS immunoreactivity in the cardiomyocytes (white arrows); (C) doxorubicin plus cannabidiol group showing a significant reduction in iNOS immunostaining. Brown color indicates iNOS positivity; (D) percentage expression of iNOS, data is mean ± S.E.M. of 8 rats, ND = non-detectable, *p < 0.05 vs. control group, •p < 0.05 vs. doxorubicin (DOX) group without cannabidiol (CBD) treatment. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
- Fig. 3. Immunohistochemical staining of nuclear factor-κB (NF-κB) in rat heart (200×) from: (A) control group showing no expression of NF-κB; (B) doxorubicin group without cannabidiol treatment showing a significant increase in NF-κB immunoreactivity in the cardiomyocytes (white arrows); (C) doxorubicin plus cannabidiol group demonstrating a significant reduction in NF-κB immunostaining. Brown color indicates NF-κB positivity; (D) percentage expression of NF-κB, data is mean ± S.E.M. of 8 rats, ND = non-detectable, *p < 0.05 vs. control group, •p < 0.05 vs. doxorubicin (DOX) group without cannabidiol (CBD) treatment. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
- Fig. 4. Immunohistochemical staining of Fas ligand (FasL) in rat heart (200×) from: (A) control group showing no expression of FasL; (B) doxorubicin group without cannabidiol treatment showing a significant increase in FasL immunoreactivity in the cardiomyocytes (white arrows); (C) doxorubicin plus cannabidiol group demonstrating a significant reduction in FasL immunostaining. Brown color indicates FasL positivity; (D) percentage expression of FasL, data is mean ± S.E.M. of 8 rats, ND = non-detectable, *p < 0.05 vs. control group, •p < 0.05 vs. doxorubicin (DOX) group without cannabidiol (CBD) treatment. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
- Fig. 5. Immunohistochemical staining of survivin in rat heart (200×) from: (A) control group showing that survivin is expressed in normal cardiomyocytes (white arrows); (B) doxorubicin group without cannabidiol treatment showing a significant reduction in survivin immunoreactivity in the cardiomyocytes; (C) doxorubicin plus cannabidiol group showing a significant increase in survivin immunostaining. Brown color indicates survivin positivity; (D) percentage expression of survivin, data is mean ± S.E.M. of 8 rats, ND = non-detectable, *p < 0.05 vs. control group, •p < 0.05 vs. doxorubicin (DOX) group without cannabidiol (CBD) treatment. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
- Fig. 6. Immunohistochemical staining of caspase-3 in rat heart (200×) from: (A) control group showing no expression of caspase-3; (B) doxorubicin group without cannabidiol treatment showing a significant increase in caspase-3 immunoreactivity in the cardiomyocytes (white arrows); (C) doxorubicin plus cannabidiol group showing a significant reduction in caspase-3 immunostaining. Brown color indicates caspase-3 positivity; (D) percentage expression of caspase-3, data is mean ± S.E.M. of 8 rats, ND = non-detectable, *p < 0.05 vs. control group, •p < 0.05 vs. doxorubicin (DOX) group without cannabidiol (CBD) treatment. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
- Table 1. Effects of cannabidiol (CBD) treatment on serum creatine kinase-MB (CK-MB) and troponin T, and cardiac tissue levels of malondialdehyde (MDA), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in rats exposed to doxorubicin (DOX) cardioxicity.
- All the values are expressed as mean ± S.E.M., n = 8 in each group. ND = non-detectable.
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- Table 2. Effects of cannabidiol (CBD) treatment on cardiac calcium, selenium and zinc ion concentrations in rats exposed to doxorubicin (DOX) cardiotoxicity.
- All the values are expressed as mean ± S.E.M., n = 8 in each group.
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- Corresponding author at: Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia. Tel.: +966 501776517.
Copyright © 2013 Elsevier B.V. All rights reserved.
