Adriamycin (ADR) is a potent anticancer
drug. Its clinical applications are limited due to its
cardiotoxicity. Oxidative stress is responsible for
cardiomyopathy induced by ADR. Previous studies have demonstrated that
davallialactone (
DAVA), extracted from mushroom Inonotus xeranticus, has potential antiplatelet aggregation activity and
free radical scavenging properties. In this study, we investigated whether
DAVA has protective effects against ADR-induced
free radical accumulation and apoptosis in cardiac muscle cells and compared the effects of
DAVA with
N-acetylcysteine, a potent
antioxidant. We evaluated the effect of
DAVA on ADR-induced cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and
crystal violet staining, the
reactive oxygen species (ROS) production by flow cytometry, and the expression of stress-related
proteins like
Cu/Zn superoxide dismutase (SOD),
Mn-SOD, and the involvement of
mitogen-activated protein kinase pathway by Western blot analysis. Apoptosis was assessed by nuclear condensation and the expression levels of
pro-apoptotic proteins, such as
caspase-3 and
polyadenosine diphosphate-
ribose polymerase (PARP). The cardio-protective effects of
DAVA were also evaluated in an in vivo study in an animal model of ADR-induced acute
cardiomyopathy. Our results showed that
DAVA significantly increased the viability of
doxorubicin-injured H9c2 cells and inhibited ADR-induced ROS production, apoptosis, and the expression of Cu/Zn SOD and
Mn-SOD.
DAVA also inhibited the expression of
extracellular signal-regulated kinase (ERK) and
c-Jun N-terminal kinase (JNK), which was activated by ADR. In the in vivo animal model, treatment involving
DAVA significantly reduced cardiomyocyte lesions. These results suggest that
DAVA is a potentially
protective agent for ADR-induced
cardiotoxicity in cardiomyocytes and can be a potential candidate to protect against
cardiotoxicity in ADR-treated
cancer patients.