Oxidative Medicine and Cellular Longevity / 2016 / Article / Tab 1

Review Article

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

Table 1

Phytochemicals investigated for renoprotective actions against cisplatin- (CSP-) induced nephrotoxicity.

PhytochemicalDose, duration, and route of administrationAnimal modelCisplatin dose and route of administrationKey findingsReference

NIF1 and 23-hydroxytormentic acid10 mg/kg/day, orally (PO) for 14 days intraperitoneally (i.p.)Sprague Dawley (SD) rats7 mg/kg, i.p. BUN and serum creatinine
MDA production and GSH depletion

6-Gingerol 12.5, 25, and 50 mg/kg for 5 days (before and after treatment), i.p.Wistar rats5 mg/kg, i.p. oxidative stress[17]

6-Hydroxy-1-methylindole-3-acetonitrile5 and 10 mg/kg, single dose, POLLC-PK1 cells and SD rats7 mg/kg, i.p. BUN, creatinine, and urinary LDH
HO-1 expression, activities of SOD, CAT, GR, MDA, and GSH

-Caryophyllene 1–10 mg/kg, i.p. single doseC57BL/6J mice25 mg/kg, i.p. inflammation and dysfunction
NOX-2 and NOX-4 expression, 4-HNE, 3-NT accumulation, and cell death

Berberine 1–3 mg/kg, single dose, i.p.BALB/cN mice13 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

Bixin 2.5 and 5 mg/kg
for 3 days, i.p.
Wistar rats5 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 mice12–18 mg/kg,
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 ester10 μM/kg, single dose, i.p.Wistar Albino rats7 mg/kg, i.p. BUN, tubular damage, and oxidative tissue damage
antioxidant enzymes

Cannabidiol 2.5–10 mg/kg, i.p. (before and after treatment)C57BL/6J mice20 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

Capsaicin5 and 10 mg/kg, PO
for 6 days, i.p.
SD rats5 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 mice5 mg/kg, i.p. HO-1 expression[39]

Cardamonin10 and 30 mg/kg, PO for 2 weeksAlbino rats7 mg/kg, i.p. SOD, GSH
NOX-1, caspase-3 expression, and Bax/Bcl-2 ratio

Carnosic acid 100 mg/kg, PO for 10 daysWistar rats7.5 mg/kg, i.p. BUN, creatinine, and MDA
GSH levels, catalase, SOD, GST, GPx, and GR activities
caspase-3 activity, apoptosis, and renal damage

Chrysin 25 or 50 mg/kg
14 days, i.p.
Wistar rats7.5 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 rats5 mg/kg, i.p. urea, creatinine, and MDA content
GSH levels, SOD, CAT, and GPx activities

Curcumin100 mg/kg
10 days, i.p.
Wistar rats7 mg/kg, i.p. MDA
NAMPT, SIRT1, SIRT3, and SIRT4 levels
100 mg/kg, i.p.C57BL/6J mice20 mg/kg, i.p. renal TNF-α, MCP-1, and ICAM-1 mRNA expression[54]
8 mg/kgWistar rats5 mg/kg, i.p. creatinine, TBARS, and MDA[51]

Cyanidin 10, 20, and 40 µg/mLHK-2 cells8 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

Decursin 20–80 mMPrimary HRCs20–80 mM catalase, SOD, and GPx activities
caspases 3 and 9, PARP, DNA fragmentation, and apoptosis
10–40 mg/kg
3 days, i.p.
SD rats5.2 mg/kg, i.p. BUN and creatinine[60]

Ellagic acid 10 and 30 mg/kg
9 days, i.p.
SD rats6 mg/kg, i.p. creatinine, urea, and kidney injury
total antioxidant status and GSH
10 mg/kg
10 days, i.p.
SD rats7 mg/kg, i.p. MDA levels and improved antioxidant enzymes
tubular necrosis and tubular dilatation

Emodin 10 mg/kg for 9 days, i.p.Wistar rats6 mg/kg, i.p. GSH, TAC, GST, GPx, GR, SOD, and CAT
NAG, creatinine, and urea concentration

Epigallocatechin-3-gallatel00 mg orally, 2 daysWistar rats7 mg/kg, i.p. SOD, CAT, GPx, and GSH
NF-κB and 4HNE
100 mg/kg i.p., single doseC57BL/6 mice20 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

Ginsenosides 10–60 µg/mLLLC-PK1 cells25 and 500 µM LDH leakage, renal damage, and apoptosis[7880]

Glycyrrhizic acid 75 and 150 mg/kg for 7 days, i.p.BALB/c and Swiss Albino mice7 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 rats7.5 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 mice5 mg/kg, i.p. BUN, creatinine, nitrite, and tissue MDA and ROS[87]

Licochalcone A1 mg/kg for
15 days, i.p.
BALB/c mice5 mg/kg, i.p. BUN, creatinine, nitrite, and MDA[89]

Ligustrazine 50 and 100 mg/kg, 7 days, i.p.SD rats8 mg/kg, i.p. urinary protein excretion, NAG excretion, creatinine, and BUN
GSH levels, SOD, and GST activities
tubular cell apoptosis

Luteolin10 mg/kg
3 days, i.p.
BALB/cN mice10 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
50 mg/kg
3 days, i.p.
C57BL/6J mice20 mg/kg, i.p. CYP2E1, Bcl-2, 4-HNE, 3-NT, NF-κB, and caspase-3
MRP4 and MRP2 expression

Lycopene6 mg/kg
10 days, i.p.
Wistar rats7 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

Naringenin 20 mg  kg−1 day−1, PO for 10 daysWistar Albino rats7 mg/kg, intravenous (i.v.) urea, creatinine, sodium excretion, and renal lipid peroxides
GST activity and renal antioxidant enzymes

Paeonol 20 mg/kg
3 days, i.p.
BALB/c mice10–30 mg/kg I.P. creatinine, BUN, TNF-α, and IL-1β[102]

Penta-O-galloyl-β-D-glucose 20–80 µMPrimary HRC40 µM cytotoxicity, apoptosis, PARP cleavage, Bax, and caspase-3
cytochrome C translocation and ROS production

Platycodin D0.1, 1, and 5 mg/kg for 3 days, i.p.ICR mice20 mg/kg, i.p. BUN, creatinine, TBARS, NF-κB activation,
GSH, GPx, and SOD

Quercetin100 mg/kg
30 days
Albino rats12 mg/kg i.p. GSH, GPX, SOD, CAT, GR, XO, TOS, and TAC
BUN, creatinine, LPO, H2O2, and tubular cell necrosis
50 mg/kg
3 days
Wistar rats5 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
50 and 100 mg/kg
9 days, i.p.
Fischer-F344 rats7.5 mg/kg, i.p. caspase-3/7 activity and DNA fragmentation[148]

Resveratrol25 mg/kg
single dose, i.p.
Albino mice5 mg/kg, i.p. creatinine, MDA, and LDH leakage[115]
10 mg/kg, 7 daysC57BL/6 mice and20 mg/kg, i.p. inflammation and necrosis[116]
30 μg/mL, i.p.Fischer rat kidney in vitro7.5/15 μg/mL, i.p. acetylation of p53 and SIRT1[117]

Rosmarinic acid 1, 2, and 5 mg/kg
2 days, i.p.
BALB/cN mice13 mg/kg, i.p. creatinine and BUN
CYP2E1, HO-1, and 4-HNE expression
NFκB and cleaved caspase-3 expression

Rutin75 and 150 mg/kg
21 days
Wistar rats7 mg/kg, i.p. BUN, creatinine, H2O2, LDH, caspase-3, NFκB, and TNF-α level[122]
30 mg/kg
14 days
SD rats5 mg/kg, i.p. membrane integrity, GSH, XO, and GGT[86]

Schizandrin and schizandrin B10, 25, 50 mg/kg
15 days, i.p.
BALB/c mice10 mg/kg, i.p. NFκB activation and p53 activation[124]

Silibinin200 mg/kg
single dose, i.p.
Wistar rats5 mg/kg, i.p. creatinine clearance
glomerular and proximal tubular function
[127, 128]

Sulforaphane500 μg/kg/day i.v. for 3 daysWistar rats7.5 mg/kg, i.p. p38 MAPK and renal adhesion molecule expressions[130]
500 μg/kg/day i.p. for 3 daysWistar rats10 mg/kg, i.p. inflammatory cell infiltration[131]

Tannic acid 40 and 80 mg/kg
7 days, i.p.
Swiss Albino mice7 mg/kg, i.p. BUN, creatinine, p38 MAPK phosphorylation, and PARP cleavage
XOR and LPO; G6PD, QR, and catalase activities

Thymoquinone50 mg/L in drinking water for 5 daysWistar Albino rats and Swiss Albino mice5, 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

Xanthorrhizol 100 and 200 mg/kg
for 4 days, i.p.
ICR mice45 mg/kg, i.p. BUN, creatinine, and lipid peroxides[143]

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