Table 2.
Characteristics and implications of mtDNA-sensing pathways targeted by pharmacological modulators in acute and chronic kidney diseases.
| Agent | Mechanism | Model | Administration | Effect | Refs |
|---|---|---|---|---|---|
| MitoTEMPO | Mitochondria-targeted antioxidant | Iohexol (HK-2 cell) | Preincubation for 4 h before culture with iohexol | Prevented RTEC apoptosis | [83] |
| IRI (mouse) | One direct injection into each kidney after reperfusion followed by five daily i.p. injections | Ameliorated AKI | [118] | ||
| MitoQ | Mitochondria-targeted antioxidant | LPS (rat) | i.v. injection after LPS injection | Ameliorated AKI | [115] |
| IRI (mouse) | i.v. injection 15 min before ischemia | Ameliorated AKI | [116] | ||
| SS-31 | Mitochondria-targeted antioxidant | IRI (rat) | Subcutaneously injection 30 min before ischemia and at the onset of reperfusion | Ameliorated AKI | [117] |
| SkQR1 | Mitochondria-targeted antioxidant | LPS (newborn rat) | i.p. administration 3 h before LPS treatment | Ameliorated AKI | [114] |
| Diazoxide | KATP channel opener, reducing ROS accumulation | IRI (rat) | Muscle injection before ischemia | Ameliorated AKI | [119] |
| Formoterol | β2-Adrenergic agonist, inducing MB | IRI (mouse) | i.p. injection starting at 24 h after reperfusion, daily for five days | Promoted AKI recovery | [122] |
| LY344864 | 5-HT1F receptor agonist, inducing MB | IRI (mouse) | i.p. injection starting at 24 h after reperfusion, daily for five days | Promoted AKI recovery | [123] |
| DNase | Enzyme for mtDNA degradation | MTD (mouse) | Incubation with MTD | Abolished renal mitochondrial injury | [14] |
| Cyclosporin A | mPTP inhibitor | Albumin (mPTC) | Preincubation for 30 min before albumin treatment | Attenuated renal tubular injury in CKD | [95] |
| H154 | TLR9 inhibitor | CLP (mouse) | i.p. administration immediately after CLP surgery | Ameliorated AKI | [78] |
| C-176 | STING inhibitor | Cisplatin (mouse) | i.p. injection 1 h before cisplatin injection | Ameliorated AKI | [15] |
Note: 5-HT1F, 5-hydroxytryptamine 1F; AKI, acute kidney injury; CKD, chronic kidney disease; CLP, cecal ligation and puncture; i.p., intraperitoneal; i.v., intravenous; IRI, ischemia/reperfusion injury; MB, mitochondrial biogenesis; mPTC, mouse proximal tubular cells; mPTP, mitochondrial permeability transition pore; MTD, mitochondrial debris; mtDNA, mitochondrial DNA; RTEC, renal tubular epithelial cells; STING, stimulator of interferon; TLR9, Toll-like receptor 9.