Figure 6. Edaravone as a mitochondrial metabolism enhancer.

• A, B
  The schematic illustrates the screening process of 702 drugs related to the mitochondrial respiratory capacity assessed by Seahorse XFe96 in C₂C₁₂ myocytes. Palmitate is used as a substrate. A total of 41 hits were identified. Maximum respiration (Max R, % of untreated cells) of compounds categorized by their therapeutic use (B).
• C, D
  The schematic illustrates the screening process of the 41 hits on FFA β‐oxidation using 9,10³H(N) palmitic acid as a substrate in C₂C₁₂ myocytes. Ten enhancers were identified. (D) Correlation between the maximum respiration (x) and palmitate β‐oxidation (y). Colors identify classes of pharmaceuticals as in (B). Edaravone was selected as a hit.
• E
  Representative respiratory profile of C₂C₁₂ myocytes treated (green trace) or not treated (black trace) with 2 μM edaravone. The CPT1 inhibitor etomoxir was used as a negative control. OCR, oxygen consumption rate; OL, oligomycin; DNP, 2,4‐dinitrophenol; Rot, rotenone; Ant A, antimycin A. Quantification in right histogram. Bars are the mean ± SEM of 12 replicas/condition.
• F, G
  FFA β‐oxidation in C₂C₁₂ myocytes transfected with CRL or ATPIF1_H49K plasmids (F) and in primary myotubes from wt and Low_OXPHOS mice (G), treated (green bars) or not with 2 μM edaravone. Bars are the mean ± SEM of n = 3 experiments, 9 replicas/condition.

Data information: (E–G) *P < 0.05 when compared to wt by ANOVA and Student's t‐test.