Bradykinin protects against DDP-induced GP-H1 cell damage via activation of PI3K/Akt/NO signaling pathway

To investigate the effect of bradykinin (BK) on cisplatin (DDP)-induced cardiotoxicity at the cellular level and its cytological mechanism. The toxic effects of DDP on GP-H1 cells, and the effects of BK on DDP cardiomyocyte survival rate, DDP-induced malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), reactive oxygen species (ROS), mitochondria membrane potential (MMP) and apoptosis were explored. DDP at different concentrations inhibited GP-H1 cells at 12 h after administration, and the inhibitory effect was more prominent at 24 h after administration and continued until 72 h after administration. The severity of GP-H1 cell damage induced by DDP was reduced by 0.1 μM, 1 μM, and 10 μM BK. After GP-H1 cells were treated with DDP, ROS levels increased and MMP levels decreased, while BK intervention inhibited these effects. At 24 h after DDP treatment, Bax/bcl-2 increased in GP-H1 cells, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. After intervention with BK, it was shown that Bax/Bcl-2 was significantly reduced, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. Bax/Bcl-2 and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 of GP-H1 cells were basically not affected by BK alone. The protective effect of BK on DDP-induced GP-H1 cell damage in guinea pig is related to the activation of PI3K/Akt/NO signaling pathway by BK, which reduces oxidative stress levels in cardiomyocytes and also acts as an anti-apoptotic agent.