Table 2.
NAC protective effects in kidney damage models in cell lines
| Pathology | Cell model | Damage scheme | (NAC) IC50/EC50 | Time points and scheme of application | Protective effects | Other effects | Ref. |
|---|---|---|---|---|---|---|---|
| Nephrotoxicity and obstructive nephropathy | Rat kidney proximal tubule (NRK-52E) cell line | 1.5 μM of cadmium in DMEM containing 2% FBS for 24 h. | 10000 μmol/l | Pretreatment for 1 h | ↑ Cell viability ↓ Intracellular and mitochondrial ROS - Restored mitochondrial morphology ↑ SIRT1 ↑ PGC-1 (α and β) |
Senescence: ↑ Cells in cell cycle phases G0/G1 ↓ Cells in cell cycle phases S and G2/M ↓ SA-β-Gal-positive areas ↓ p53 and p21 |
Dong et al.57 |
| HK-2 and NRK-52E cell lines | High levels of folic acid (≥200 μM) for 3–6 mo | 25 μmol/l | Coincubation for 72 h | Restored PARP1 and ↑ cyclin D1, Bcl-2, GP×1, and MnSOD expression ↓ Epithelial-mesenchymal transition |
↓ FA-induced genotoxicity | Kandel et al.54 | |
| Nephrotoxicity | HK-2 cell line | 0,625-10 μM of vancomycin for 24 h. To measure ROS, it was 6 h |
5000 μmol/l | Pretreatment for 2 h | ↑ Cell viability ↓ KIM-1 ↓ NGAL ↓ Bax/Bcl-2 ↓ Caspase 3 ↓ ROS ↓ p-P38 ↓ p-JNK |
Yu et al.61 | |
| NRK-52E cells line | 300–600 μM of uranyl acetate for 6, 12, 18, and 24 h | 2000 μmol/l | Pretreatment for 1 h | ↓ Apoptosis ↓ ROS ↓ GRP78 ↓ CHOP ↓ Caspase 12 ↓ Caspase 3 ↑ p-PI3K |
Hu et al.53 | ||
| PK15 cell line | Fusarium toxins (0.25–8 μM of DON, 5–160 μM ZEN, and 5–160 μM FB1) in serum-free media for 24 h. | 500 μmol/l | Coadministration for 24 h | ↓ Cell death ↑ GR ↑ SOD ↓ MDA ↓ ROS ↓ mRNA levels of Bax ↑ mRNA levels and expression of Bcl-2 ↓ mRNA levels and expression of caspase-3 ↓ mRNA levels of caspase-9 ↓ mRNA levels of cytochrome-c ↓ mRNA levels of p53 |
Zhang et al.60 | ||
| Kidney injury and diabetic kidney disease | NRK-52E cells line starved for 6 h | High concentrations of glucose (30 mM) for 48 h | 2000 μmol/l | Pretreatment for 48 h. | ↓ ROS ↑ p-RIPK1 and p-RIPK3 ↓ mRNA level of MCP-1 ↓ IL-1β |
Guo et al.62 | |
| Senescence | NRK-52E cell line | 20 μM of cisplatin for 6 h | 10000 μmol/l | Pretreatment for 1 h | ↓ IL-1β ↓ IL-6 ↓ TNF-α ↓ Intracellular and mitochondrial ROS ↑ PGC-1 (α and β) ↑ mRNA levels of UCP2, COX-IV, ATP5α, TFAM, NRF1 ↑ SIRT1 ↓ acetyl-p53 |
Senescence: ↓ SA-β-Gal-positive area ↓ p53 ↓ p21 |
Li et al.47 |
(acetyl) p53, (acetylated) tumor suppressor P53; (Mn)SOD, (manganese) superoxide dismutase; (p)-JNK, (phosphorylated) c-Jun N-terminal kinases; (p)-RIPK1, (phosphorylated) receptor-interacting protein kinase 1; (p)-RIPK3, (phosphorylated) receptor-interacting protein kinase 3; (p)-PI3K, (phosphorylated) phosphatidylinositol 3-kinase; (NAC), N-acetylcysteine concentration; ATP, adenosine triphosphate; ATP5α, ATP synthase F1 subunit alpha; Bax, Bcl-2 associated X-protein; Bcl-2, B-cell lymphoma (2); CHOP, C/EBP homologous protein; COX-IV, cytochrome c oxidase IV; DMEM, Dulbecco's Modified Eagle Medium; DON, deoxynivalenol; FA, Fatty acids; FB1, fumonisin B1; FBS, fetal bovine serum; GP×1, glutathione peroxidase 1; GR, glutathione reductase; GRP78, glucose-regulated protein 78; HK-2, proximal tubule epithelial cell line; IL-1β, interleukin-1-beta; IL-6, interleukin-6; KIM-1, kidney injury molecule 1; MCP-1, monocyte chemoattractant protein 1; MDA, malondialdehyde; NAC, N-acetylcysteine; NGAL, neutrophil gelatinase associated lipocalin; NRF1, nuclear respiratory factor 1; NRK-52E, rat kidney proximal tubule cells; p21, cyclin-dependent kinase inhibitor 1; PARP1, poly (ADP-ribose) polymerase 1; PGC-1 (α and β), peroxisome proliferator-activated receptor-gamma coactivator; p-P38, phosphorylated P38 mitogen-activated protein kinase; ROS, reactive oxygen species; SA-β-Gal, senescence-associated beta-galactosidase; SIRT1, sirtuin 1; TDCPP, Tris(1,3-dichloroisopropyl) phosphate; TFAM, mitochondrial transcription factor A; TNF-α, tumor necrosis factor alpha; UCP2, uncoupling protein 2; ZEN, zearalenone.