A number of studies have demonstrated that
inflammation plays a role in
doxorubicin (DOX)-induced
cardiotoxicity. However, the molecular mechanism by which DOX induces cardiac
inflammation has yet to be fully elucidated. The present study aimed to investigate the role of the
p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in DOX-induced
inflammation and cytotoxicity. The results of our study demonstrated that the exposure of H9c2 cardiac cells to DOX reduced cell viability and stimulated an inflammatory response, as demonstrated by an increase in the levels of interleukin-1β (IL-1β) and
IL-6, as well as
tumor necrosis factor-α (TNF-α) production. Notably, DOX exposure induced the overexpression of phosphorylated
p38 MAPK and phosphorylation of the NF-κB p65 subunit, which was markedly inhibited by
SB203580, a specific inhibitor of
p38 MAPK. The inhibition of NF-κB by
pyrrolidine dithiocarbamate (
PDTC), a selective inhibitor of NF-κB, significantly ameliorated DOX-induced
inflammation, leading to a decrease in the levels of IL-1β and
IL-6, as well as TNF-α production in H9c2 cells. The pretreatment of H9c2 cells with either
SB203580 or
PDTC before exposure to DOX significantly attenuated DOX-induced cytotoxicity. In conclusion, our study provides novel data demonstrating that the
p38 MAPK/NF-κB pathway is important in the induction of DOX-induced
inflammation and cytotoxicity in H9c2 cardiac myocytes.