| | 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] |
| | -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- 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- 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] |
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