Abstract
Introduction: This study aimed to investigate the possible effect of gastrodin in renal ischemia-reperfusion injury (IRI) and the mechanisms. Methods: Forty-eight male Sprague Dawley rats were randomly divided into 3 groups: sham-operated group, saline-treated IRI group, and gastrodin-treated IRI group. Gastrodin or 0.9% saline (300 mg/kg/day) was intragastrically administrated for 8 days before operation. We analyzed renal function and histological change. The malondialdehyde level, antioxidant enzymes’ activities, and markers of inflammation and apoptosis were measured. Statistical analysis was performed using 1-way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA on ranks. Results: Gastrodin pretreatment improved IRI-induced renal dysfunction and histologic injury. Mechanistically, gastrodin reversed the elevation of malondialdehyde level and the reduction of antioxidant enzymes’ activities. Gastrodin also reduced the elevated myeloperoxidase activity, TNF-α and IL-1β levels, and the activation of p38 MAPK. Moreover, gastrodin-treated rats exhibited a dramatic reduction in renal tubular apoptosis, along with a decrease in caspase-3 activation and an increase in the Bcl-2/Bax ratio. Conclusion: Gastrodin pretreatment may alleviate renal IRI via the amelioration of oxidative injury, inflammatory response, and renal tubular apoptosis.
References
1.
Lameire
NH
, Bagga
A
, Cruz
D
, De Maeseneer
J
, Endre
Z
, Kellum
JA
, Acute kidney injury: an increasing global concern
. Lancet
. 2013 Jul
;382
(9887
):170
–9
.2.
Ronco
C
, Bellomo
R
, Kellum
JA
. Acute kidney injury
. Lancet
. 2019 Nov
;394
(10212
):1949
–64
. .3.
Uchino
S
, Kellum
JA
, Bellomo
R
, Doig
GS
, Morimatsu
H
, Morgera
S
, Acute renal failure in critically ill patients: a multinational, multicenter study
. JAMA
. 2005 Aug
;294
(7
):813
–8
.4.
Bonventre
JV
, Yang
L
. Cellular pathophysiology of ischemic acute kidney injury
. J Clin Invest
. 2011 Nov
;121
(11
):4210
–21
. .5.
Paller
MS
, Hoidal
JR
, Ferris
TF
. Oxygen free radicals in ischemic acute renal failure in the rat
. J Clin Invest
. 1984 Oct
;74
(4
):1156
–64
. .6.
Lum
H
, Roebuck
KA
. Oxidant stress and endothelial cell dysfunction
. Am J Physiol Cell Physiol
. 2001 Apr
;280
(4
):C719
–41
. .7.
Liang
HL
, Hilton
G
, Mortensen
J
, Regner
K
, Johnson
CP
, Nilakantan
V
. MnTMPyP, a cell-permeant SOD mimetic, reduces oxidative stress and apoptosis following renal ischemia-reperfusion
. Am J Physiol Renal Physiol
. 2009 Feb
;296
(2
):F266
–76
. .8.
Ratnam
DV
, Ankola
DD
, Bhardwaj
V
, Sahana
DK
, Kumar
MN
. Role of antioxidants in prophylaxis and therapy: a pharmaceutical perspective
. J Control Release
. 2006 Jul
;113
(3
):189
–207
. .9.
Han
X
, Shi
H
, Liu
K
, Zhong
L
, Wang
F
, You
Q
. Protective effect of gastrodin on myocardial ischemia-reperfusion injury and the expression of Bax and Bcl-2
. Exp Ther Med
. 2019 Jun
;17
(6
):4389
–94
. .10.
Peng
Z
, Wang
H
, Zhang
R
, Chen
Y
, Xue
F
, Nie
H
, Gastrodin ameliorates anxiety-like behaviors and inhibits IL-1beta level and p38 MAPK phosphorylation of hippocampus in the rat model of posttraumatic stress disorder
. Physiol Res
. 2013
;62
(5
):537
–45
.11.
Peng
Z
, Wang
S
, Chen
G
, Cai
M
, Liu
R
, Deng
J
, Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway
. Neurochem Res
. 2015 Apr
;40
(4
):661
–73
.12.
Tian
ZK
, Zhang
YJ
, Feng
ZJ
, Jiang
H
, Cheng
C
, Sun
JM
, Nephroprotective effect of gastrodin against lead-induced oxidative stress and inflammation in mice by the GSH, Trx, Nrf2 antioxidant system, and the HMGB1 pathway
. Toxicol Res
. 2021 Mar
;10
(2
):249
–63
.13.
Ma
JQ
, Sun
YZ
, Ming
QL
, Tian
ZK
, Zhang
YJ
, Liu
CM
. Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway
. Food Funct
. 2020 May
;11
(5
):4615
–24
. .14.
Sun
B
, Jiang
J
, Zhu
X
, Yang
D
, Cui
Z
, Zhang
Y
, Protective effects of gastrodin pretreatment on mouse hepatic ischemia-reperfusion occurring through antioxidant and anti-apoptotic mechanisms
. Exp Ther Med
. 2021 May
;21
(5
):471
.15.
Daemen
MA
, vanʼt Veer
C
, Denecker
G
, Heemskerk
VH
, Wolfs
TG
, Clauss
M
, Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation
. J Clin Invest
. 1999 Sep
;104
(5
):541
–9
.16.
Letavernier
E
, Perez
J
, Joye
E
, Bellocq
A
, Fouqueray
B
, Haymann
JP
, Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure
. J Am Soc Nephrol
. 2005 Aug
;16
(8
):2395
–402
.17.
Ma
D
, Lim
T
, Xu
J
, Tang
H
, Wan
Y
, Zhao
H
, Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1alpha activation
. J Am Soc Nephrol
. 2009 Apr
;20
(4
):713
–20
.18.
Zheng
Y
, Lu
M
, Ma
L
, Zhang
S
, Qiu
M
, Wang
Y
. Osthole ameliorates renal ischemia-reperfusion injury in rats
. J Surg Res
. 2013 Jul
;183
(1
):347
–54
. .19.
Weight
SC
, Furness
PN
, Nicholson
ML
. New model of renal warm ischaemia-reperfusion injury for comparative functional, morphological and pathophysiological studies
. Br J Surg
. 1998 Dec
;85
(12
):1669
–73
. .20.
Chatterjee
PK
. Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review
. Naunyn Schmiedebergs Arch Pharmacol
. 2007 Oct
;376
(1–2
):1
–43
. .21.
Daemen
MA
, de Vries
B
, Buurman
WA
. Apoptosis and inflammation in renal reperfusion injury
. Transplantation
. 2002 Jun
;73
(11
):1693
–700
. .22.
Green
DR
, Reed
JC
. Mitochondria and apoptosis
. Science
. 1998 Aug
;281
(5381
):1309
–12
. .23.
Shimizu
S
, Narita
M
, Tsujimoto
Y
. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC
. Nature
. 1999 Jun
;399
(6735
):483
–7
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