Table 1.
Phytochemicals investigated for renoprotective actions against cisplatin- (CSP-) induced nephrotoxicity.
| Phytochemical | Dose, duration, and route of administration | Animal model | Cisplatin dose and route of administration | Key findings | Reference |
|---|---|---|---|---|---|
| NIF1 and 23-hydroxytormentic acid | 10 mg/kg/day, orally (PO) for 14 days intraperitoneally (i.p.) | Sprague Dawley (SD) rats | 7 mg/kg, i.p. | ↓ BUN and serum creatinine ↓ MDA production and GSH depletion |
[14] |
|
| |||||
| 6-Gingerol | 12.5, 25, and 50 mg/kg for 5 days (before and after treatment), i.p. | Wistar rats | 5 mg/kg, i.p. | ↓ oxidative stress | [17] |
|
| |||||
| 6-Hydroxy-1-methylindole-3-acetonitrile | 5 and 10 mg/kg, single dose, PO | LLC-PK1 cells and SD rats | 7 mg/kg, i.p. | ↓ BUN, creatinine, and urinary LDH ↑ HO-1 expression, activities of SOD, CAT, GR, MDA, and GSH |
[19] |
|
| |||||
| β-Caryophyllene | 1–10 mg/kg, i.p. single dose | C57BL/6J mice | 25 mg/kg, i.p. | ↓ inflammation and dysfunction ↓ NOX-2 and NOX-4 expression, 4-HNE, 3-NT accumulation, and cell death |
[23] |
|
| |||||
| Berberine | 1–3 mg/kg, single dose, i.p. | BALB/cN mice | 13 mg/kg, i.p. | ↓ BUN, creatinine, and oxidative/nitrosative stress ↓ NF-κB, TNF-α, COX-2, iNOS, and histopathological changes ↓ p53 and active caspase-3 |
[27] |
|
| |||||
| Bixin | 2.5 and 5 mg/kg for 3 days, i.p. |
Wistar rats | 5 mg/kg, i.p. | ↓ lipid peroxidation and renal glutathione depletion ↓ chromosome aberrations |
[29, 30] |
|
| |||||
| C-Phycocyanin | 5–50 mg/kg, i.p. | C57BL/6J and CD1 mice | 12–18 mg/kg, i.p. |
↓ BUN, creatinine, oxidative stress, and apoptosis ↓ p-ERK, p-JNK, and p-p38 expression and Bax, caspase-9, and caspase-3 activation |
[31, 32] |
|
| |||||
| Caffeic acid phenethyl ester | 10 μM/kg, single dose, i.p. | Wistar Albino rats | 7 mg/kg, i.p. | ↓ BUN, tubular damage, and oxidative tissue damage ↑ antioxidant enzymes |
[33] |
|
| |||||
| Cannabidiol | 2.5–10 mg/kg, i.p. (before and after treatment) | C57BL/6J mice | 20 mg/kg, i.p. | ↓ BUN, creatinine, ROS formation, and 3-NT ↓ PARP, caspase-3/7, and DNA fragmentation ↓ mRNA of TNF-α and IL1 and iNOS and protein expression |
[36] |
|
| |||||
| Capsaicin | 5 and 10 mg/kg, PO for 6 days, i.p. |
SD rats | 5 mg/kg, i.p. | ↓ BUN, creatinine, MDA, and renal damage | [38] |
| 2.5, 5, and 10 mg/kg for 5 days, i.p. | C57BL/6 mice | 5 mg/kg, i.p. | ↑ HO-1 expression | [39] | |
|
| |||||
| Cardamonin | 10 and 30 mg/kg, PO for 2 weeks | Albino rats | 7 mg/kg, i.p. | ↑ SOD, GSH ↓ NOX-1, caspase-3 expression, and Bax/Bcl-2 ratio |
[41] |
|
| |||||
| Carnosic acid | 100 mg/kg, PO for 10 days | Wistar rats | 7.5 mg/kg, i.p. | ↓ BUN, creatinine, and MDA ↑ GSH levels, catalase, SOD, GST, GPx, and GR activities ↓ caspase-3 activity, apoptosis, and renal damage |
[45] |
|
| |||||
| Chrysin | 25 or 50 mg/kg 14 days, i.p. |
Wistar rats | 7.5 mg/kg, i.p. | ↓ oxidative stress and apoptosis | [47] |
|
| |||||
| Cinnamic acid (CA) and cinnamaldehyde (CD) | CA, 50 mg/kg CD, 40 mg/kg, PO for 7 days |
SD rats | 5 mg/kg, i.p. | ↓ urea, creatinine, and MDA content ↑ GSH levels, SOD, CAT, and GPx activities |
[49] |
|
| |||||
| Curcumin | 100 mg/kg 10 days, i.p. |
Wistar rats | 7 mg/kg, i.p. | ↓ MDA ↑ NAMPT, SIRT1, SIRT3, and SIRT4 levels |
[56] |
| 100 mg/kg, i.p. | C57BL/6J mice | 20 mg/kg, i.p. | ↓ renal TNF-α, MCP-1, and ICAM-1 mRNA expression | [54] | |
| 8 mg/kg | Wistar rats | 5 mg/kg, i.p. | ↓ creatinine, TBARS, and MDA | [51] | |
|
| |||||
| Cyanidin | 10, 20, and 40 µg/mL | HK-2 cells | 8 µg/mL | ↓ BUN, creatinine, MDA, renal index, and IL-6 ↓ GRP78, p-ERK, caspase-12, and PARP cleavage ↓ apoptosis, DNA damage, ERK activation, and AKT inhibition |
[58] |
|
| |||||
| Decursin | 20–80 mM | Primary HRCs | 20–80 mM | ↑ catalase, SOD, and GPx activities ↓ caspases 3 and 9, PARP, DNA fragmentation, and apoptosis |
[59] |
| 10–40 mg/kg 3 days, i.p. |
SD rats | 5.2 mg/kg, i.p. | ↓ BUN and creatinine | [60] | |
|
| |||||
| Ellagic acid | 10 and 30 mg/kg 9 days, i.p. |
SD rats | 6 mg/kg, i.p. | ↓ creatinine, urea, and kidney injury ↑ total antioxidant status and GSH |
[63] |
| 10 mg/kg 10 days, i.p. |
SD rats | 7 mg/kg, i.p. | ↓ MDA levels and improved antioxidant enzymes ↓ tubular necrosis and tubular dilatation |
[65] | |
|
| |||||
| Emodin | 10 mg/kg for 9 days, i.p. | Wistar rats | 6 mg/kg, i.p. | ↑ GSH, TAC, GST, GPx, GR, SOD, and CAT ↓ NAG, creatinine, and urea concentration |
[69] |
|
| |||||
| Epigallocatechin-3-gallate | l00 mg orally, 2 days | Wistar rats | 7 mg/kg, i.p. | ↑ SOD, CAT, GPx, and GSH ↓ NF-κB and 4HNE |
[72] |
| 100 mg/kg i.p., single dose | C57BL/6 mice | 20 mg/kg, i.p. | ↓ p-ERK, GRP78, caspase-12, Fas-L, BAX, and apoptosis | [75, 76] | |
|
| |||||
| Genistein | 10 mg/kg 3 days 25 µg/L |
C57BL/6 mice HK-2 cells |
20 mg/kg, i.p. 1 µg/mL |
↓ BUN, creatinine, ROS production, tubular damage, and necrosis score ↓ ICAM-1 and MCP-1 expression and NF-κB activation ↓ apoptosis and p53 induction |
[77] |
|
| |||||
| Ginsenosides | 10–60 µg/mL | LLC-PK1 cells | 25 and 500 µM | ↓ LDH leakage, renal damage, and apoptosis | [78–80] |
|
| |||||
| Glycyrrhizic acid | 75 and 150 mg/kg for 7 days, i.p. | BALB/c and Swiss Albino mice | 7 mg/kg, i.p. | ↑ GSH, GR, GST, catalase, and GPx activities ↓ BUN and creatinine |
[82, 84] |
|
| |||||
| Hesperidin | 100 and 200 mg/kg 10 days, i.p. |
Wistar rats | 7.5 mg/kg, i.p. | ↓ BUN, creatinine, and DNA degradation ↑ SOD, GPx, GST, GR, GSH, and catalase activities and vitamin C levels ↓ renal TNF-α levels |
[85, 86] |
|
| |||||
| Isoliquiritigenin | 1 mg/kg for 15 days, i.p. |
BALB/c mice | 5 mg/kg, i.p. | ↓ BUN, creatinine, nitrite, and tissue MDA and ROS | [87] |
|
| |||||
| Licochalcone A | 1 mg/kg for 15 days, i.p. |
BALB/c mice | 5 mg/kg, i.p. | ↓ BUN, creatinine, nitrite, and MDA | [89] |
|
| |||||
| Ligustrazine | 50 and 100 mg/kg, 7 days, i.p. | SD rats | 8 mg/kg, i.p. | ↓ urinary protein excretion, NAG excretion, creatinine, and BUN ↑ GSH levels, SOD, and GST activities ↓ tubular cell apoptosis |
[90] |
|
| |||||
| Luteolin | 10 mg/kg 3 days, i.p. |
BALB/cN mice | 10 and 20 mg/kg, i.p. | ↓ renal dysfunction, tubular injury, oxidative stress, BUN, and creatinine ↑ GSH, SOD, and catalase ↓ p53 activation and PUMA-α protein expression |
[92] |
| 50 mg/kg 3 days, i.p. |
C57BL/6J mice | 20 mg/kg, i.p. | ↓ CYP2E1, Bcl-2, 4-HNE, 3-NT, NF-κB, and caspase-3 ↓ MRP4 and MRP2 expression |
[93] | |
|
| |||||
| Lycopene | 6 mg/kg 10 days, i.p. |
Wistar rats | 7 mg/kg, i.p. | ↓ urea and creatinine and MRP2 and MRP4 expression ↑ OAT1, OAT3, OCT1, OCT2, Nrf2, and Bcl-2 expression |
[96, 97] |
| 4 mg/kg 5 days, i.p. |
SD and Wistar rats | ↑ catalase, GPx, and SOD activities ↓ NF-κB, HSP 60 and HSP 70, and Bax expression |
[98] | ||
|
| |||||
| Naringenin | 20 mg · kg−1 · day−1, PO for 10 days | Wistar Albino rats | 7 mg/kg, intravenous (i.v.) | ↓ urea, creatinine, sodium excretion, and renal lipid peroxides ↑ GST activity and renal antioxidant enzymes |
[101] |
|
| |||||
| Paeonol | 20 mg/kg 3 days, i.p. |
BALB/c mice | 10–30 mg/kg I.P. | ↓ creatinine, BUN, TNF-α, and IL-1β | [102] |
|
| |||||
| Penta-O-galloyl-β-D-glucose | 20–80 µM | Primary HRC | 40 µM | ↓ cytotoxicity, apoptosis, PARP cleavage, Bax, and caspase-3 ↓ cytochrome C translocation and ROS production |
[106] |
|
| |||||
| Platycodin D | 0.1, 1, and 5 mg/kg for 3 days, i.p. | ICR mice | 20 mg/kg, i.p. | ↓ BUN, creatinine, TBARS, NF-κB activation, ↑ GSH, GPx, and SOD |
[108] |
|
| |||||
| Quercetin | 100 mg/kg 30 days |
Albino rats | 12 mg/kg i.p. | ↑ GSH, GPX, SOD, CAT, GR, XO, TOS, and TAC ↓ BUN, creatinine, LPO, H2O2, and tubular cell necrosis |
[110] |
| 50 mg/kg 3 days |
Wistar rats | 5 mg/kg, i.p. | ↓ Na and K excretion, NAG, LDH, ALP, GGT, and KIM-1 ↓ GSH/GSSG ratio, NFκB, iNOS, ICAM-1, VCAM-1, and renal MPO |
[111] | |
| 50 and 100 mg/kg 9 days, i.p. |
Fischer-F344 rats | 7.5 mg/kg, i.p. | ↓ caspase-3/7 activity and DNA fragmentation | [148] | |
|
| |||||
| Resveratrol | 25 mg/kg single dose, i.p. |
Albino mice | 5 mg/kg, i.p. | ↓ creatinine, MDA, and LDH leakage | [115] |
| 10 mg/kg, 7 days | C57BL/6 mice and | 20 mg/kg, i.p. | ↓ inflammation and necrosis | [116] | |
| 30 μg/mL, i.p. | Fischer rat kidney in vitro | 7.5/15 μg/mL, i.p. | ↓ acetylation of p53 and SIRT1 | [117] | |
|
| |||||
| Rosmarinic acid | 1, 2, and 5 mg/kg 2 days, i.p. |
BALB/cN mice | 13 mg/kg, i.p. | ↓ creatinine and BUN ↓ CYP2E1, HO-1, and 4-HNE expression ↓ NFκB and cleaved caspase-3 expression |
[120] |
|
| |||||
| Rutin | 75 and 150 mg/kg 21 days |
Wistar rats | 7 mg/kg, i.p. | ↓ BUN, creatinine, H2O2, LDH, caspase-3, NFκB, and TNF-α level | [122] |
| 30 mg/kg 14 days |
SD rats | 5 mg/kg, i.p. | ↑ membrane integrity, GSH, XO, and GGT | [86] | |
|
| |||||
| Schizandrin and schizandrin B | 10, 25, 50 mg/kg 15 days, i.p. |
BALB/c mice | 10 mg/kg, i.p. | ↓ NFκB activation and p53 activation | [124] |
|
| |||||
| Silibinin | 200 mg/kg single dose, i.p. |
Wistar rats | 5 mg/kg, i.p. | ↑ creatinine clearance ↑ glomerular and proximal tubular function |
[127, 128] |
|
| |||||
| Sulforaphane | 500 μg/kg/day i.v. for 3 days | Wistar rats | 7.5 mg/kg, i.p. | ↓ p38 MAPK and renal adhesion molecule expressions | [130] |
| 500 μg/kg/day i.p. for 3 days | Wistar rats | 10 mg/kg, i.p. | ↓ inflammatory cell infiltration | [131] | |
|
| |||||
| Tannic acid | 40 and 80 mg/kg 7 days, i.p. |
Swiss Albino mice | 7 mg/kg, i.p. | ↓ BUN, creatinine, p38 MAPK phosphorylation, and PARP cleavage ↓ XOR and LPO; ↑ G6PD, QR, and catalase activities |
[136] |
|
| |||||
| Thymoquinone | 50 mg/L in drinking water for 5 days | Wistar Albino rats and Swiss Albino mice | 5, 7, and 14 mg/kg i.v. in rats i.p. in mice |
↓ urea, creatinine, MDA, 8-isoprostane, MRP2, and MRP4 ↑ OAT1, OAT3, OCT1, and OCT2 and survival rate of animals |
[139] |
|
| |||||
| Xanthorrhizol | 100 and 200 mg/kg for 4 days, i.p. |
ICR mice | 45 mg/kg, i.p. | ↓ BUN, creatinine, and lipid peroxides | [143] |