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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Cannabidiol mediates beneficial effects on the microvasculature of murine hearts with regard to irradiation-induced inflammation and early signs of fibrosis.
Radiation 5:17 (2025)
Verlagsversion
DOI
Objective: Radiotherapy administered to control thoracic cancers results
in a partial irradiation of the heart at mean doses up to 19 Gy, which
increases the risk of developing a spectrum of cardiovascular diseases
known as radiation-induced heart disease (RIHD). As inflammation is a
major driver of the development of RIHD, we investigated the potential
of the anti-inflammatory agent cannabidiol (CBD) to attenuate
irradiation-induced cardiovascular damage in vivo. Methods: Female
C57BL/6 mice were given daily injections of CBD (i.p., 20 mg/kg body
weight) for 4 weeks beginning either 2 weeks prior to 16 Gy irradiation
of the heart or at the time of irradiation. Mice were sacrificed 30 min
and 2, 4, and 10 weeks after irradiation to investigate the expression
of inflammatory markers and stress proteins in primary cardiac
endothelial cells (ECs). DNA double-strand breaks, immune cell
infiltration, and signs of fibrosis were studied in explanted heart
tissue. Results: We showed that the irradiation-induced upregulation of
the inflammatory markers ICAM-1 and MCAM was only attenuated when
treatment with CBD was started 2 weeks prior to irradiation but not when
the CBD treatment was started concomitant with irradiation of the
heart. The protective effect of CBD was associated with a decrease in
irradiation-induced DNA damage and an increased expression of protective
heat shock proteins (Hsp), such as Hsp32/Heme-oxygenase-1 (HO-1) and
Hsp70, in the heart tissue. While the upregulation of the inflammatory
markers ICAM-1 and MCAM, expression was prevented up to 10 weeks after
irradiation by CBD pre-treatment, and the expression of VCAM-1, which
started to increase 10 weeks after irradiation, was further upregulated
in CBD pre-treated mice. Despite this finding, 10 weeks after heart
irradiation, immune cell infiltration and fibrosis markers of the heart
were significantly reduced in CBD pre-treated mice. Conclusion: CBD
treatment before irradiation mediates beneficial effects on murine
hearts of mice, resulting in a reduction of radiation-induced
complications, such as vascular inflammation, immune cell infiltration,
and fibrosis.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
radiotherapy; cannabidiol (CBD); irradiation-induced heart disease; vascular inflammation; fibrosis
ISSN (print) / ISBN
2673-592X
e-ISSN
2673-592X
Zeitschrift
Radiation
Quellenangaben
Band: 5,
Heft: 2,
Artikelnummer: 17
Verlag
MDPI
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed