THE LACK OF PROTECTION OF ISCHEMIC POSTCONDITIONING IN DYSLIPIDEMIC MICE IS RESTORED WITH N-ACETYLCYSTEINE TREATMENT

MAZO TAMARA; YANAJE C YOHANA; PEREZ, MARÍA VIRGINIA; TAMARA ZAOBORNYJ; BARCHUK MAGALI; BERG GABRIELA; MARÍA CARLA GRECO; GEORGINA OSSANI; NESTOR LAGO; TRIPODI VALERIA; CONTIN MARIO; DANNUNZIO, VERÓNICA; GELPI RICARDO

Congreso; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2019; 2019

Dyslipidemia per se exacerbated ischemia/reperfusion (I/R) injury, mainly caused by an increased of reactive oxygen species increases infarct size (MI). Ischemic postconditioning (IP) decreases MI, but we proved that in mice fed a high-fat diet (HFD, 12 weeks) with atherosclerosis in the early stages, the protective effect of IP is abolished. Therefore, the objective of our work is to evaluate the effect of treatment (T) with n-acetyl cysteine (NAC) restores the cardioprotective effect of IP in HFD mice. Male C57/BL6 mice (20 g) were divided into a control diet group (CD) and HFD group. In the last 3 weeks of feeding, a subgroup was treated with NAC (10 mM). Hearts were subjected to 30 min of I and 120 min R (Langendorff Technique). In the IP group, after I, 6 cycles of R/I were performed. The biochemical profile, histological alterations, ventricular function and MI were evaluated. Data are expressed as mean ± SEM and p ?0.05 was considered statistically significant (n= 6 per group). There was a slight decrease in weight in the NAC group without variation in daily caloric intake, cholesterol levels and triglycerides. NAC reduced the moderate hepatic steatosis in HFD group. As we expected, IP reduced MI in CD group (I/R: 54.3 ± 2.3 vs. IP: 36.5 ± 1.8; p?0.05), but this protection was abolished in the HFD-IP group (I/R: 66.4 ± 3.8 vs. IP: 62.1 ± 3.6). NAC T reduced MI in CD-IP+NAC with respect to the CD-I/R group and the CD-I/R+NAC group (I/R: 54.3 ± 2.3; I/R+NAC: 36.3 ± 4.6 vs. PI+NAC: 19.2 ± 3.3; p<0.05). On the other hand, in both NAC groups we observed a significant decrease in MI (HFD-I/R+NAC: 39.7 ± 4.5; HFD-IP+NAC: 26.4 ± 2.0; p?0.05 vs. HFD-IP and HFD-I/R). Regarding left ventricular function, we did not observe a significant difference between the groups after 30 min of I evaluated at 60 min after R. This study showed that alterations in the redox state in an early stage of atherosclerosis were enough to abolish the protective effect of IP, however T with NAC restored the cardioprotective effect of IP.