Table 1.
Identification and change trend of biomarkers.
| Mode | Metabolites | RT (min) | Measured Mass (Da) | Mass Error (ppm) | AE | EMD | DOX | Pathway |
|---|---|---|---|---|---|---|---|---|
| ESI+ | Spermine | 0.50 | 203.2238 | 1.0 | ↓ * | - | ↓ *** | Polyamine metabolism |
| Arginine | 0.65 | 174.1128 | 6.3 | - | - | ↓ ** | Arginine biosynthesis | |
| Creatine | 0.45 | 132.1000 | −8.3 | ↓ * | - | ↓ ** | Glycine, serine, and threonine metabolism | |
| Methionine | 1.12 | 150.0589 | 0.0 | ↓ * | - | ↓ ** | Methionine cycle | |
| Glutathione | 1.39 | 308.0916 | 0.0 | ↓ ** | ↓ * | ↓ ** | Glutathione metabolism | |
| Isoleucine | 1.93 | 132.1031 | 4.5 | ↑ *** | - | ↑ *** | Valine, leucine, and isoleucine degradation | |
| 2-phenylglycine | 2.16 | 152.0700 | 4.8 | - | - | ↑ ** | - | |
| Pyridoxine | 2.16 | 170.0825 | 4.7 | ↑ * | - | ↑ *** | Vitamin B6 metabolism | |
| Adenine | 1.26 | 136.0630 | 5.1 | ↓ ** | - | ↓ *** | Purine metabolism | |
| ADP | 4.47 | 428.0375 | 0.7 | ↓ * | - | ↓ * | Purine metabolism | |
| Oxidized glutathione | 4.47 | 613.1589 | −1.5 | ↑ * | ↑ * | ↑ * | Glutathione metabolism | |
| Phenylalanine | 4.70 | 166.0876 | 4.8 | ↑ *** | ↑ * | ↑ *** | Phenylalanine metabolism | |
| Guanine | 4.70 | 152.0580 | 5.3 | - | ↑ ** | - | Purine metabolism | |
| 1H-indole-3-carboxaldehyde | 5.29 | 146.0614 | 5.5 | ↑ * | - | ↑ *** | Tryptophan metabolism | |
| Indoleacrylic acid | 5.29 | 188.0723 | 5.8 | ↑ ** | - | ↑ *** | Tryptophan metabolism | |
| Phytosphingosine | 9.54 | 318.3009 | 0.3 | ↑ *** | ↑ * | ↑ *** | Sphingolipid metabolism | |
| ESI− | Glutamic acid | 0.73 | 146.0455 | 1.4 | - | - | ↓ *** | D-glutamine and D-glutamate metabolism |
| Tyrosine | 2.49 | 180.0662 | 0.6 | ↑ *** | - | ↑ *** | Tyrosine metabolism | |
| Xanthine | 2.49 | 151.0257 | 0.7 | ↓ *** | - | ↓ *** | Purine metabolism | |
| Glutathione | 1.39 | 306.0759 | −0.3 | ↓ * | ↓ * | ↓ *** | Glutathione metabolism | |
| Oxidized glutathione | 4.47 | 611.1439 | −0.3 | ↑ * | - | ↓ * | Glutathione metabolism | |
| Malic acid | 0.88 | 133.0130 | −5.3 | ↓ *** | ↓ * | ↓ *** | Citrate cycle (TCA cycle) | |
| Phenylalanine | 4.62 | 164.0720 | 4.8 | ↑ ** | ↑ * | ↑ *** | Phenylalanine metabolism | |
| Hypoxanthine | 1.93 | 135.0308 | 0.7 | ↓ *** | ↓ * | ↓ *** | Purine metabolism | |
| Tryptophan | 5.29 | 203.0820 | −0.5 | ↑ ** | - | ↑ *** | Tryptophan metabolism | |
| Pantothenic acid | 4.96 | 218.1029 | 0.5 | ↑ *** | ↓ * | ↑ *** | Pantothenate and CoA biosynthesis | |
| Azelaic acid | 7.12 | 187.0970 | 0.0 | ↑ * | - | ↑ * | - | |
| S-adenosylhomo-cysteine | 4.47 | 383.1134 | −1.0 | ↓ * | ↓ * | ↓ *** | Methionine cycle | |
| Cytosine | 0.88 | 110.0356 | 1.8 | ↓ * | - | ↓ *** | Pyrimidine metabolism | |
| N-formyl-L-glutamic acid | 1.26 | 174.0402 | 0.0 | ↓ *** | ↑ *** | ↓ *** | Histidine metabolism | |
| Folic acid | 5.47 | 440.1315 | −0.9 | ↑ ** | - | ↑ *** | Folate biosynthesis | |
| Inosine | 4.62 | 267.0735 | 2.2 | ↑ * | - | ↑ ** | Purine metabolism | |
| Citric acid | 1.72 | 191.0192 | 0.0 | ↑ * | - | ↑ * | Citrate cycle (TCA cycle) | |
| Guanosine | 4.62 | 282.0839 | 0.4 | ↓ * | ↓ * | ↓ * | Purine metabolism |
* p < 0.05, ** p < 0.01, *** p < 0.001 compared with control group. ↑, ↓ represent the increase and decrease of metabolites compared with the control group, respectively.