Indole 6 Carboxaldehyde Prevents Oxidative Stress-Induced Mitochondrial Dysfunction, DNA Damage and Apoptosis in C2C12 Skeletal Myoblasts

Abstract

Abstract Objectives Indole-6-carboxaldehyde (I6CA) is an indole derivative derived from the brown algae Sargassum thunbergii, and some pharmacological activity is known, but the antioxidant effect of I6CA has not been reported. In the present study, the protective capacity of I6CA against oxidative stress-induced cytotoxicity in C2C12 skeletal myoblasts was investigated. Methods I6CA's effect on hydrogen peroxide (H2O2)-disrupted cell viability, mitochondrial function, and intracellular ATP level was measured. Furthermore, I6CA's potency to reduce H2O2-induced DNA damage, reactive oxygen species (ROS) generation, AMP-activated protein kinase (AMPK) activation and apoptosis was monitored. Results The results indicate that preincubation of cells with I6CA prior to H2O2 stimulation resulted in significant inhibition of cytotoxicity and DNA damage associated with the inhibition of ROS generation. In addition, H2O2-induced loss of mitochondrial membrane potential and cytosolic release of cytochrome c were significantly protected in the presence of I6CA. I6CA also attenuated the decrease in ATP content by H2O2 and restored H2O2-induced activation of AMPK, indicating that I6CA maintains energy metabolism through the preservation of mitochondrial function while eliminating the ROS generated by H2O2. Furthermore, I6CA rescued C2C12 cells from H2O2-triggered apoptosis, as evidenced by reduced caspase-3 activation, PARP degradation and DNA fragmentation. Conclusions Collectively, our findings conclude that I6CA effectively protected C2C12 myoblasts against oxidative damage, at least in part, by preventing mitochondrial-dependent pathway through scavenging excessive ROS. Funding Sources The research was supported by the Basic Science Research Program through the National Research Foundation of Korea grant funded by the Korea government (2018R1A2B2005705).