Atrial disorders are often asymptomatic but can lead to serious complications, such as heart failure. One of the most common atrial disorders is arrhythmia, a condition characterized by an irregular heartbeat that impairs blood circulation and reduces oxygen supply to tissues.
In this study, an in vitro model of atrial disorders was established using the immortalized HL-1 mouse atrial cardiomyocyte cell line. The response of these cells to the cardiotoxic anticancer drug doxorubicin (Dox) was evaluated in combination with the antioxidant N-acetylcysteine (NAC) and the HIF-1α inhibitor PX-478 under normoxic and hypoxic (1 % oxygen) conditions. The effects of these compounds on cell viability were assessed spectrophotometrically using Alamar Blue staining, while HIF-1α expression was evaluated via real-time PCR.
The findings indicate that the cytotoxic effects of Dox on HL-1 cells were similar under both normoxic and hypoxic conditions. The HIF-1α inhibitor PX-478 enhanced Dox-induced cytotoxicity under hypoxia, while the antioxidant NAC protected cell viability in both oxygen conditions. Under normoxia, NAC exerted its protective effect by inhibiting reactive oxygen species (ROS) formation, whereas under hypoxia, its effect was linked to the stabilization of HIF-1α and the subsequent activation of cell survival pathways. ElectroMechanoActive Polymer-based Scaffolds for Heart-on-Chip (EMAPS – Cardio)