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ORAL PRESENTATION / TAM METİN SÖZLÜ SUNUM

The effects of saffron and black cumin (Nigella sativa) on inflammatory cytokines and
oxidative stress have been investigated, revealing that both substances exhibited

therapeutic benefits by lowering TNF-α levels owing to their anti-inflammatory, antioxidant,
and immunomodulatory characteristics (Vafaeipour et al., 2023).

Caspase-3, the terminal effector enzyme of the apoptotic cascade, mediates

programmed cell death through DNA fragmentation and the proteolytic cleavage of
structural proteins. Activation of caspase-3 can occur directly in response to toxic

compounds or indirectly through TNF-α signalling xenobiotic exposure to cardiomyocyte
injury. In our study, doxorubicin exposure increased caspase-3 mRNA expression, whereas

pretreatment with BSO (20 and 40 µg/ml) significantly suppressed its expression in a
doxorubicin-induced cardiotoxicity model. Previous studies have similarly reported that plant

extracts such as saffron (Crocus sativus), wild blueberry, and black blueberry extract reduce

doxorubicin- or norepinephrine-induced caspase-3 activation in H9c2 cells (Chahine et al.,
2016; Sun et al., 2019; Türck et al., 2022).

These findings suggest that BSO offers cardioprotective benefits mainly by reducing
NF-κB- and TNF-α-mediated inflammatory signaling and curbing apoptosis through the

downregulation of caspase-3. This mechanistic understanding highlights BSO's role in
modulating key molecular pathways involved in doxorubicin-induced cardiotoxicity and lays

the groundwork for further exploration of its molecular targets and signaling networks.

FINANCIAL SUPPORT
This research received no grant from any funding agency/sector.

CONFLICT OF INTEREST
The authors declared that there is no conflict of interest.

REFERENCES

Bergmann M, Loser P, Dietz R, Harsdorf R. (2001). Effect of NF-κB Inhibition on TNF-α-induced
Apoptosis and Downstream Pathways in Cardiomyocytes. Journal of Molecular and Cellular
Cardiology. 33(6):1223-1232.
Birdal O, Ferah Okkay I, Okkay U, Bayram C, Mokthare B, Ertugrul MS, Hacimuftuoglu A, Aksakal E,
Koza Y, Saygi M, Senocak H. (2024). Protective effects of arbutin against doxorubicin-induced
cardiac damage. Molecular Biology Reports. 51(1):532.

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