We investigated the potential protective effect of rutinum (RUT) against
pirarubicin- (THP-) induced
cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a
cardioprotective agent dexrazoxane (DZR) prior to treatment with THP. Some of the cells were preincubated with RUT and a
p38 mitogen-activated protein kinase (MAPK) inhibitor,
SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30-70 μM, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50 μM. Administration of RUT and
SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-β1, p-p38 MAPK, cleaved
Caspase-9,
Caspase-7, and
Caspase-3. A synergistic effect was observed on coadministration of RUT and
SB203580. RUT protected against THP-induced
cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-β1-p38 MAPK signaling pathway.