Table 1.
Proteomic Changes for Specific Nephrotoxicants
| Nephrotoxicant | Model | Method | Representative Protein Biomarker Changes | Time course | Reference |
|---|---|---|---|---|---|
| Acyclovir | Mouse kidney | 2-DE, MALDI-TOF-MS, IHC | ↓VEGF, ↓VEGFR, ↑MHC class II antigen, ↑glyoxalase 1, ↑peroxiredoxin 1,↑αB-crystallin, ↑fibroblast growth factor receptor 1-IIIb, ↓cytochrome c oxidase subunit Vb | 9 days | [15] |
| Amphotericin B | Human urine | ELISA | NGAL | Up to 14 days | [16] |
| Carboplatin | HK-2 cells | 2-DE, MALDI-TOF/TOF MS/MS | ↓Elongation factor 1-α1 (EF1A1), ↓ATP synthase subunit α (ATPA), ↓serine hydroxymethyltransferase (GLYM), ↑thioredoxin-dependent peroxide reductase (PRDX3), ↑headcase protein homolog (HDC), ↑α-enolase (ENOA), ↑heat shock protein 60kDa/70kDa (Hsp60/70) | 24 h | [17] |
| Cisplatin | HK-2 Cells | 2-DE, MALDI-TOF/TOF MS/MS | ↓Elongation factor 1-α1 (EF1A1), ↑ATP synthase subunit α (ATPA), ↑serine hydroxymethyltransferase (GLYM), ↓thioredoxin-dependent peroxide reductase (PRDX3), ↑headcase protein homolog (HDC), ↓α-enolase (ENOA), ↑heat shock protein 60kDa/70kDa (Hsp60/70) | 24 h | [17] |
| Cisplatin | RPTEC/TERT1 cells | iTRAQ/HPLC-MS | ↑Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ↑alpha-enolase (ENO1), ↑elongation factor 2 (EEF2), ↓NADH dehydrogenase 1 (NDUFB6), ↓protein DJ-1 (PARK7), ↓apoptosis-inducing factor 1 (AIFM1), ↓cytochromes b and c (UQCRC1, CYCS), ↑ Superoxide dismutase 1/2 (SOD1/2), ↑peroxiredoxin 1 | 14 days | [18] |
| Cisplatin | Rat urine | ELISA, fluorimetric activity | ↑urinary Glutamyl aminopeptidase (GluAp) activity, ↑GluAp by ELISA | 24 h | [19] |
| Cisplatin | Rat urine | ELISA, iTRAQ, MALDI TOF LC-MS/MS | ↑Nestin, ↑fetuin-A, ↑hamartin, ↑T-kininogen | 5 day | [20] |
| Cisplatin | Rat urine and kidney | IHC, 1-DE | Organic anion transporter 5 (Oat5) | 48 h | [21] |
| Cisplatin | Mouse kidney and urine | 1-DE | Transglutaminase 1 | 1–3 days | [22] |
| Cyclosporine | Rat kidney – salt depletion | 2-DE, LC-MS/MS | ↓fructose-1,6-bisphosphatase (FBP), ↓CD147, ↓Phospho-protein kinase B (AKT), ↓Phospho-IKappa gamma kinase (IKKɣ), ↓Phospho-nuclear factor κβ (NF-κβ) p-65, ↑chloride intracellular channel 1 (CLIC1), ↓PDZK1, ↓aquaporin 1, ↓Superoxide dismutase 2 (SOD2), ↑phospho-Janus kinase 2 JAK2, ↑phospho- Signal transducer and activator of transcription 3 (STAT3) | 28 days | [27] |
| Cyclosporine | Rat kidney | 2-DE, LC-MS/MS | ↑Vimentin, ↑caldesmon, actin binding protein 1/3 (ABP1/3), ↑plastin 3T, ↓regucalcin, ↓calbindin, ↓NADH-ubiquinone oxidoreductase (NADH-UO), ↑pyruvate kinase, ↓kidney aminoacylase I (KA-1), ↑fructose-1,6-bisphosphatase | 28 days | [26] |
| Cyclosporine | HEK-293 cells | SILAC, LC-MALDI-TOF/TOF | ↑cyclophillin A/B, ↑macrophage migration inhibitor, ↓galectin-3-binding protein, ↓ a disintegrin and metalloproteinase with thrombospondin motif S1 (ADAMTS1), ↓collagen α-1 (II, IV), ↓fibrinogen, ↓cystatin c, ↓fibrillin-2, ↓Titin, ↓ɣ-glutamyl hydrolase, ↓Insulin growth factor binding protein 2/5 (IGFBP2/5), ↓clusterin, ↓Beta-2 microglobulin (β2MG), ↓apolipoprotein E | 24 h | [25] |
| Cyclosporine | Rat plasma | MALDI-TOF-MS, ESI-TOF-MS/MS | ↑Alpha-1-acid glycoprotein (AAG), ↑clusterin (CLUS), ↓haptoglobin (Hp) | 7 days | [29] |
| Cyclosporine | Rat kidney | 2-DE, MALDI-TOF-MS | ↓Calbindin, ↓alpha-2µ-globulin | 14 days | [28] |
| Gentamicin | Rat urine | LC-MS/MS | ↑Collagen 1A1/2A1/3A1, 1A2 (COL1A1/2A1/3A1/1A2), ↑fetuin-A (FETUA), ↑Apolipoprotein A4 (APOA4), ↑Fibrinogen beta chain (FIBB), ↑Osteopontin (OSTP), ↑Epidermal growth factor (EGF), ↑Tropomyosin 1 (TPM1), ↑Thyroid hormone receptor beta (THRB), ↑albumin, ↑clusterin | 3 days | [31] |
| Gentamicin | Rat kidney | 2-DE, MALDI-TOF | ↑plasma retinol binding protein 4 (PRBP4), ↓glycine amidinotransferase (AGAT), ↓catalase, ↓glutathione peroxidase 1, ↓peroxiredoxin-1 | 14 days | [36] |
| Gentamicin | Rat urine | 2-DE, LC-ESI QUAD TOF | ↑regenerating islet-derived protein IIIβ (Reg IIIb), ↑gelsolin, ↑N-acetyl-beta D glucosaminidase (NAG), ↑Kidney injury molecule 1 (KIM-1), ↑Neutrophil gelatinase associated lipocalin (NGAL), ↑Plasminogen activator inhibitor 1 (PAI-1) | 3 days | [30] |
| Gentamicin | Rat kidney | IMS | ↑transthyretin | 7 days | [37] |
| Gentamicin | Rat urine | 2-DE, MALDI-TOF-MS | ↑albumin, ↑hemopexin, ↑transferrin, ↑vitamin D binding protein | 7 days | [32] |
| Gentamicin | Rat urine and kidney | Luminex, IHC | ↑Kidney injury molecule 1 (KIM-1) | 72 h | [33] |
| Gentamicin | Monkey urine | ELISA and Luminex | ↑microalbumin, ↑α-1 microglobulin, ↑clusterin, ↑osteopontin | 7 days | [34] |
| Gentamicin | Dog urine | ELISA | ↑ Neutrophil gelatinase associated lipocalin (NGAL), ↑clusterin | 1–3 days | [35] |
| NSAIDS | Human urine | 1-DE, Q-TOF-LC/MS | ↑Tamm-Horsfall protein (UROM), ↑ AMBP alpha-1-microglobulin/bikunin precursor (AMBP), ↑ Zinc alpha 2-glycoprotein (ZAZG), ↑ Inter-Alpha-Trypsin Inhibitor Heavy Chain Family Member 4 (ITIH4), ↑ Immunoglobulin Kappa Constant (IGKC), ↑Cystatin M/C (CYTM/C) | NR | [38] |
| NSAIDS | Human urine | 2-DE, SELDI-TOF-MS | ↑albumin, ↑ Alpha-1 Antitrypsin (A1AT), ↑Apolipoprotein H (APOH), ↑Beta actin (ACTB), ↑Beta 2-microglobulin (B2MG), ↑ Prostaglandin D2 Synthase (PTGDS), ↑ Basement membrane-specific heparan sulfate proteoglycan core protein (PGBM), ↑Transthyretin (TTHY), ↑Fatty acid binding protein 5 (FABP5) | NR | [39] |
Abbreviations: ELISA, enzyme linked immunosorbent assay; IHC, immunohistochemistry; LC, liquid chromatography; MALDI-TOF, matrix assisted laser desorption/ionization time of flight; MHC, major histocompatibility complex; MS, mass spectrometry; MSI, mass spectrometry imaging; NanoESI, nano-electrospray ionization; NGAL, neutrophil gelatinase-associated lipocalin; RPTEC, renal proximal tubule epithelial cells; SILAC, stable isotope labeling with amino acids in cell culture; VEGF/R, vascular endothelial growth factor/receptor.