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

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).