Dexmedetomidine alleviates H 2 O 2 -induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells

Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has protective effect on oxidative stress induced cell apoptosis, but effects of Dex and Dex-mediated α2-AR activation on oxidant induced necroptosis was unclear. H9C2 cardiomyocytes were pre-treated with or without Dex and α2-AR antagonist yohimbine hydrochloride (YOH) before being exposed to H 2 O 2 to induce oxidative cellular damage. Cell viability and lactate dehydrogenase (LDH) were detected by ELISA kits, protein expressions of Heme Oxygenase 1(HO-1), receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) were observed by WB, and TUNEL was used to detected cell apoptosis. H 2 O 2 significantly decreased cell viability and increased LDH release and necroptotic and apoptotic cell deaths (all p < 0.05, H 2 O 2 vs. Control). Dex preconditioning alleviated these injuries induced by H 2 O 2 . Dex preconditioning significantly increased expression of protein HO-1 and decreased expressions of proteins RIPK1 and RIPK3 induced by H 2 O 2 , while all these protective effects of Dex were reversed by YOH (all p < 0.05, Dex + H 2 O 2 vs. H 2 O 2 ; and YOH + Dex + H 2 O 2 vs. Dex + H 2 O 2 ). However, YOH did not prevent this protective effect of Dex against H 2 O 2 induced apoptosis (YOH + Dex + H 2 O 2 vs. Dex + H 2 O 2 , p > 0.05). These findings indicated that Dex attenuates H 2 O 2 induced cardiomyocyte necroptotic and apoptotic cell death respectively dependently and independently of α2-AR activation.