Research Article
Dexmedetomidine Pretreatment Attenuates
Kidney Injury and Oxidative Stress during Orthotopic
Autologous Liver Transplantation in Rats
Xiaofang Yu,
1,2
Xinjin Chi,
1
Shan Wu,
1
Yi Jin,
3
Hui Yao,
1
Yiheng Wang,
1,4
Zhengyuan Xia,
5
and Jun Cai
1
1
Department of Anesthesiology, Tird Afliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China
2
Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
3
Department of Pathology, Tird Afliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China
4
Department of Anesthesiology, First Afliated Hospital, University of South China, Hengyang, Hunan 421001, China
5
Department of Anesthesiology, Te Second Afliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou,
Zhejiang 325027, China
Correspondence should be addressed to Zhengyuan Xia; zyxia@hku.hk and Jun Cai; gzcaijun@hotmail.com
Received 4 May 2015; Revised 2 August 2015; Accepted 3 August 2015
Academic Editor: Ryuichi Morishita
Copyright © 2016 Xiaofang Yu et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Tis paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective efects during
orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation.
Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group
D1), high dose Dex (group D2), atipamezole (a nonspecifc
2
receptor blocker) + high dose Dex (group B1), ARC239 (a specifc
2B/c
receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specifc
2A
receptor blocker) + high dose Dex (group
B3). Ten histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and
oxidants and antioxidants were performed 8 hours afer OALT. We found that pretreatment with Dex activated Nrf2 in glomerular
cells and upregulated antioxidants but reduced oxidants (all < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but
not ARC239, reversed these protective efects. In conclusion, pretreatment with Dex activates Nrf2 through
2A
receptor, increases
the antioxidant levels, and attenuates renal injury during OALT.
1. Introduction
Orthotopic liver transplantation (OLT) has been considered
the best choice for end-stage liver diseases [1]. Acute kidney
injury (AKI) is the most common and severe complication
afer OLT with a 12%–70% [2, 3] incidence rate and an annual
mortality rate of up to 35%–45% [4]. It is an important factor
in early postoperative death and infuences the prognosis and
rehabilitation of patients [5, 6]. Terefore, it is important to
try to increase the survival rate and improve the rehabilitation
afer OLT by means of controlling and/or avoiding acute kid-
ney injury in the perioperative period of liver transplantation.
Previous studies have demonstrated that the oxidative stress
injury is related to AKI afer OLT.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a
master transcriptional factor in cells, which acts against
oxidative and stress injury. It can enhance the antioxidant
enzymes and phase II detoxifcation enzyme levels in com-
bination with the antioxidant response element (ARE) and
plays a key role in the endogenous antioxidative activity
[7, 8]. Recent studies have borne out claims that it plays
an important role in preventing ischemia-reperfusion injury.
Some researchers have reported that Nrf2 can provide pro-
tective efect by upregulating the expression of heme oxyge-
nase 1 (HO-1), nicotinamide-adenine dinucleotide phosphate
Hindawi Publishing Corporation
Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 4675817, 10 pages
http://dx.doi.org/10.1155/2016/4675817