Naringin protects myocardial cells from doxorubicin-induced apoptosis partially by inhibiting the p38MAPK pathway

Doxorubicin (DOX) has been widely used to treat cancers as a first‑line antitumor drug. However, it causes severe, irreversible, dose‑dependent cardiotoxicity. To evaluate the protective effects of naringin (NRG) on cardiotoxicity, the authors investigated the molecular mechanism of the p38MAPK signaling pathway. H9c2 cells were treated for 24 h by using 5 µmol/l DOX without or with being pretreated by 1 µM NRG for 150 min or by 3 µM SB203580 for 60 min. Cell viability was detected by cell counting kit‑8 assay. Intracellular reactive oxygen species (ROS) levels were detected based on the oxidative conversion of 2',7'‑dichlorfluorescein‑diacetate (cell‑permeable) to dichlorofluorescein (fluorescent). The expression of p38MAPK was determined by western blotting. The expression level of p‑p38MAPK in H9c2 cells, which was significantly increased by exposure to 5 µM DOX for 60 min (P<0.01), was significantly decreased by pretreatment with 1 µM NRG for 150 min beforehand (P<0.01). The viability of H9c2 cells pretreated for 150 min with 1 µM NRG was significantly enhanced compared with that using DOX directly (P<0.01). Intracellular ROS levels were significantly reduced by being pretreated with 1 µM NRG for 150 min or with 3 µM SB203580 for 60 min before the cells were exposed to 5 µM DOX. Collectively, NRG protected H9c2 cells against the cardiotoxicity induced by DOX through suppressing the expression and activity of the p38MAPK pathway. The findings provided valuable evidence for the possible use of NRG to relieve DOX‑induced cardiotoxicity.