Indole-6-carboxaldehyde prevents oxidative stress-induced mitochondrial dysfunction, DNA damage and apoptosis in C2C12 skeletal myoblasts by regulating the ROS-AMPK signaling pathway

Background Indole-6-carboxaldehyde (I6CA), a natural indole derivative derived from the brown algae Sargassum thunbergii (Mertens) Kuntze, is known to have several pharmacological activities. However, the antioxidant effects of I6CA have not been identified. Objective The study aimed to investigate the protective effect of I6CA and its underlying mechanism against oxidative stress-induced damage in C2C12 mouse skeletal myoblasts. Results The findings revealed that pretreatment with I6CA protected hydrogen peroxide (H 2 O 2 )-induced cytotoxicity and DNA damage through blockage of intracellular reactive oxygen species (ROS) generation. I6CA also significantly suppressed C2C12 cells against H 2 O 2 -induced apoptosis by preventing loss of mitochondrial membrane potential and cytosolic release of cytochrome c , decreasing the rate of Bax/Bcl-2 expression and reducing the activity of caspases. In addition, I6CA markedly attenuated the decrease in ATP content induced by H 2 O 2 and restored H 2 O 2 -induced activation of AMP-activated protein kinase (AMPK). However, the cytoprotective effects of I6CA against H 2 O 2 were eliminated by compound C, a specific AMPK signaling blocker. Conclusion The current results indicate that I6CA was able to protect C2C12 myoblast DNA damage and apoptosis from oxidative stress by at least preserving mitochondrial homeostasis mediated through the ROS-AMPK signaling pathway.