Inhibition of COX-2 Activity Reduced H/R-Induced Intracellular ROS Level in H9C2 Cardiomyocytes.
Taken together, these observations suggest that inhibition of COX-2 activity protected against H/R-induced cell apoptosis through activation of Akt/iNOS/NO pathway.
However, up to now, no study has been conducted to address how inhibition of COX-2 activity couples to multiple signaling molecules and exerts cardioprotective effects.
The fact that pretreatment with NS398 can significantly reduce the above-mentioned detrimental effects of H/R stimulation and enhance posthypoxic H9C2 cardiomyocyte viability indicates that inhibition of COX-2 activity may protect against H/R-induced cell injury through attenuation of cell apoptosis.
Given the fact that prostaglandins--by the action of COX--play a key role in the generation of the inflammatory response , inhibition of COX-2 activity may attenuate H/R-induced cell apoptosis through blocking the expression of proinflammatory cytokines.
Indeed, in the current study, higher intracellular ROS level was concomitant with induction of COX-2 in H/R-stimulated H9C2 cardiomyocytes, whereas inhibition of COX-2 activity significantly alleviated ROS generation.