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ORAL PRESENTATION / TAM METİN SÖZLÜ SUNUM

Blueberry Seed Oil Suppresses NF-κB, TNF-α, and Caspase-3 Expression in
Doxorubicin-Induced Cardiotoxicity Model in H9c2 Cells

Sedat GÖKMEN 1,* Dilek GÜVENÇ
2

1 Kastamonu University, Faculty of Veterinary, Department of Pharmacology and Toxicology,
Kastamonu, TÜRKIYE
2 Ondokuz Mayıs University, Faculty of Veterinary, Department of Pharmacology and
Toxicology, Samsun, TÜRKIYE

*Correspound Author: sgokmen@kastamonu.edu.tr

Abstract

Herbal products have been used in traditional medicines worldwide for thousands of
years. These remedies have gained popularity as alternatives to conventional
pharmaceuticals. Many herbal products provide health benefits, with fewer side effects than
synthetic drugs. Phytotherapy may mitigate xenobiotic-induced cardiac-damage by
modulating inflammation and apoptosis. In this study, we investigated the protective effects
of European Blueberry (Vaccinium myrtillus L.) seed oil (BSO) in an H9c2 cell doxorubicin-
induced cardiotoxicity model. The experimental groups were designed as follows. The control
group received no treatments. For doxorubicin-exposure, H9c2 cells were exposed to 5 µM
doxorubicin for 24 h. In BSO groups, cells were pretreated with BSO (10, 20, and 40 µg/ml)
for 30 min before 5 µM doxorubicin for 24 h. Cell viability was determined using the MTT
assay. The expression levels of the inflammatory markers NF-κB and TNF-α, and the
apoptotic marker caspase-3 were quantified using Real-Time Polymerase Chain Reaction.
BSO inhibited H9c2 cell proliferation at concentrations ≥80 µg/mL (1 to 640 µg/mL), with
IC₅₀ of 147 µg/mL. Therefore, concentrations of 10, 20, and 40 µg/mL were selected for the
experiments. The findings indicated that doxorubicin treatment significantly increased the
mRNA expression levels of NF-κB, TNF-α, and caspase-3 in H9c2 cells (P<0.01, P<0.001,
and P<0.001, respectively). However, BSO significantly decreased the expression of both NF-
κB and TNF-α at 20 and 40 µg/mL compared to the doxorubicin group (NF-κB: P<0.01,
P<0.05; TNF-α: P<0.001, P<0.01, respectively). Similarly, caspase-3 expression was reduced
at these concentrations (P<0.001 and P<0.01). Notably, BSO at a concentration of 40
µg/mL reinstated the mRNA expression levels of NF-κB, TNF-α, and caspase-3 to those
observed in the control group (P>0.05). Overall, these findings indicate that blueberry seed
oil has the potential to serve as a natural therapeutic agent for mitigating doxorubicin-
induced cardiotoxicity by attenuating inflammation and apoptosis. Further research is
needed to fully elucidate the mechanisms by which blueberry seed oil exerts cardioprotective
effects.
Keywords: Antiinflammatory, apoptosis, Blueberry Seed Oil, cardioprotective, H9c2.

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