Table 2 |.
The effects of pharmacological modulation of mitochondrial quality control on AKI and repair
| Agent | Mechanism | AKI model | Administration | Effect on AKI and repair | Refs |
|---|---|---|---|---|---|
| MitoQ | Mitochondria-targeted antioxidant | IRI (mouse) | Tail vein injection 15 min before ischaemia | Attenuated AKI | 178 |
| Cisplatin (mouse) | IP administration 1 h before cisplatin administration | Attenuated AKI | 180 | ||
| Mito-CP | Mitochondria-targeted antioxidant | Cisplatin (mouse) | IP administration 1 h before cisplatin administration | Attenuated AKI | 180 |
| GC4419 | Mitochondrial-specific SOD mimetic | Cisplatin (mouse) | IP injection, once daily starting 5 days before cisplatin administration | Attenuated AKI and accelerated kidney repair | 50 |
| SkQR1 | Mitochondria-targeted antioxidant | IRI (mouse) | IP injection 3 h before ischaemia and at 1, 13, 25 and 37 h | Attenuated AKI | 179 |
| Gentamicin (mouse) | IP injection daily 3 h before gentamycin injection for 6 days | Attenuated AKI | 179 | ||
| SS-31 | Specifically binds to cardiolipin, protects cristae curvature, stabilizes mitochondrial structure, facilitates electron transport and minimizes ROS production | IRI (rat) | SC injection 30 min before ischaemia, at the onset of reperfusion and 2 h after reperfusion | Attenuated AKI | 181 |
| SC injection 30 min before ischaemia and at the onset of reperfusion | Attenuated AKI | 55,182 | |||
| Starting at the onset of reperfusion for 4 weeks using a subcutaneously implanted osmotic pump | Reduced post-AKI kidney fibrosis | 55 | |||
| Starting 1 month after ischaemia for 6 weeks using a subcutaneously implanted osmotic pump | Attenuated post-AKI kidney fibrosis | 42 | |||
| Mitochonic acid 5 | Binds to mitofilin in the IMM, facilitates ATP production | IRI (mouse) | Oral gavage 3 h before ischaemia | Attenuated AKI | 218 |
| Cisplatin (mouse) | Oral gavage starting at cisplatin injection, daily for 3 days | Attenuated AKI | 218 | ||
| mdivi-1 | Inhibits DRP1 activity and suppresses mitochondrial fission | IRI (mouse) | IP injection 1 h prior to ischaemia | Attenuated AKI | 40 |
| SRT1720 | Activates SIRT1 and induces mitochondrial biogenesis | IRI (rat) | IP injection starting at 24 h after reperfusion, daily for 2 or 5 days | Attenuated AKI | 205 |
| LY344864 | 5-HT1F agonist, induces mitochondrial biogenesis | IRI (mouse) | IP injection starting at 24 h after reperfusion, daily for 5 days | Attenuated AKI and accelerated kidney repair | 217 |
| Formoterol | β2 adrenergic receptor agonist, induces mitochondrial biogenesis | IRI (mouse) | IP administration starting at 24 h after surgery, daily for 5 days | Accelerated kidney repair | 161 |
| Niacinamide | NAD+ precursor, improves mitochondrial oxidative metabolism | IRI (mouse) | IP administration once daily for 4 days with the final dose an hour prior to surgery | Attenuated AKI | 160 |
| Single IP dose 18 h after the onset of reperfusion | Attenuated AKI | 160 | |||
| Cisplatin (mouse) | IP administration 24 h before and at the time of cisplatin administration | Attenuated AKI | 160 | ||
| TES-1025 | ACMSD inhibitor, boosts in vivo synthesis of NAD+ | Cisplatin (mouse) | Supplementation of chow diet starting 10 days before cisplatin administration | Attenuated AKI | 224 |
| IRI (mouse) | Supplementation of chow diet starting 10 days before surgery | Attenuated AKI | 224 |
5-HT1F, 5-hydroxytryptamine receptor 1F; AKI, acute kidney injury; ACMSD, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase; DRP1, dynamin-1-like protein; IMM, inner mitochondrial membrane; IP, intraperitoneal; IRI, ischaemia-reperfusion injury; NAD, nicotinamide adenine dinucleotide; ROS, reactive oxygen species; SC, subcutaneous; SOD, superoxide dismutase.