Dexmedetomidine attenuates HO-induced apoptosis of rat cardiomyocytes independently of antioxidant enzyme expression.

INTRODUCTION AND OBJECTIVES

Dexmedetomidine is a highly selective alpha-2 adrenoceptor agonist that has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effect of dexmedetomidine on cardiomyocytes remains unknown. This study mainly aimed to investigate the effects of dexmedetomidine on the generation of reactive oxygen species (ROS) in cardiomyocytes and whether it inhibits the apoptosis of cardiomyocytes by affecting antioxidant enzyme expression.

METHODS

Neonatal rat cardiomyocytes were pretreated with dexmedetomidine (100 nM) for 24 h. The cardiomyocytes were then incubated with 200 μM hydrogen peroxide solution (HO) for 4 h. PCR assay was used to determine the mRNA expression of antioxidant enzymes. Western blot assay was used to determine the protein expression of antioxidant enzymes. Fluorescence microscopy with the MitoSOX probe was used to detect the formation of ROS in cardiomyocytes, and fluorescence-activated cell sorting with annexin V/PI was used to determine the number of apoptotic cardiomyocytes.

RESULTS

Dexmedetomidine reduced ROS generation and antioxidant enzymes levels in cardiomyocytes before HO stimulation (p<0.05). However, ROS generation and apoptosis in cardiomyocytes were significantly increased after HO treatment, and dexmedetomidine pretreatment markedly inhibited the changes (p<0.05).

CONCLUSION

For the first time, to the best of our knowledge, our study shows that dexmedetomidine has a protective effect on cardiomyocytes through inhibition of ROS-induced apoptosis, and more importantly, this effect is independent of antioxidant enzyme mRNA and protein expression.