PMID- 23737979
OWN - NLM
STAT- MEDLINE
DCOM- 20140110
LR  - 20240109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Intermittent exposure to xenon protects against gentamicin-induced 
      nephrotoxicity.
PG  - e64329
LID - 10.1371/journal.pone.0064329 [doi]
LID - e64329
AB  - Aminoglycoside antibiotics, especially gentamicin, are widely used to treat 
      Gram-negative infections due to their efficacy and low cost. Nevertheless the use 
      of gentamicin is limited by its major side effect, nephrotoxicity. Xenon (Xe) 
      provided substantial organoprotective effects in acute injury of the brain and 
      the heart and protected against renal ischemic-reperfusion injury. In this study, 
      we investigated whether xenon could protect against gentamicin-induced 
      nephrotoxicity. Male Wistar rats were intermittently exposed to either 70% xenon 
      or 70% nitrogen (N2) balanced with 30% oxygen before and during gentamicin 
      administration at a dose of 100 mg/kg for 7 days to model gentamicin-induced 
      kidney injury. We observed that intermittent exposure to Xe provided 
      morphological and functional renoprotection, which was characterized by 
      attenuation of renal tubular damage, apoptosis, and oxidative stress, but not a 
      reduction in inflammation. We also found that Xe pretreatment upregulated 
      hypoxia-inducible factor 2alpha (HIF-2alpha) and its downstream effector vascular 
      endothelial growth factor, but not HIF-1alpha. With regard to the three HIF prolyl 
      hydroxylases, Xe pretreatment upregulated prolyl hydroxylase domain-containing 
      protein-2 (PHD2), suppressed PHD1, and had no influence on PHD3 in the rat 
      kidneys. Pretreatment with Xe also increased the expression of miR-21, a microRNA 
      known to have anti-apoptotic effects. These results support Xe renoprotection 
      against gentamicin-induced nephrotoxicity.
FAU - Jia, Ping
AU  - Jia P
AD  - Division of Nephrology, Zhongshan Hospital Fudan University, Shanghai, China.
FAU - Teng, Jie
AU  - Teng J
FAU - Zou, Jianzhou
AU  - Zou J
FAU - Fang, Yi
AU  - Fang Y
FAU - Jiang, Suhua
AU  - Jiang S
FAU - Yu, Xiaofang
AU  - Yu X
FAU - Kriegel, Alison J
AU  - Kriegel AJ
FAU - Liang, Mingyu
AU  - Liang M
FAU - Ding, Xiaoqiang
AU  - Ding X
LA  - eng
GR  - HL111580/HL/NHLBI NIH HHS/United States
GR  - P01 HL082798/HL/NHLBI NIH HHS/United States
GR  - HL029587/HL/NHLBI NIH HHS/United States
GR  - R21 HL111580/HL/NHLBI NIH HHS/United States
GR  - HL082798/HL/NHLBI NIH HHS/United States
GR  - P01 HL029587/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130530
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Gentamicins)
RN  - 0 (MicroRNAs)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (mirn21 microRNA, rat)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 3H3U766W84 (Xenon)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*adverse effects
MH  - Apoptosis/drug effects
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics
MH  - Cytoprotection/*drug effects
MH  - Down-Regulation/drug effects
MH  - Gentamicins/*adverse effects
MH  - Kidney/cytology/*drug effects/metabolism/physiology
MH  - Kidney Tubules/cytology/drug effects/metabolism/physiology
MH  - Male
MH  - MicroRNAs/genetics
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
MH  - Up-Regulation/drug effects
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - Xenon/*pharmacology
PMC - PMC3667819
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/06/06 06:00
MHDA- 2014/01/11 06:00
PMCR- 2013/05/30
CRDT- 2013/06/06 06:00
PHST- 2013/02/03 00:00 [received]
PHST- 2013/04/12 00:00 [accepted]
PHST- 2013/06/06 06:00 [entrez]
PHST- 2013/06/06 06:00 [pubmed]
PHST- 2014/01/11 06:00 [medline]
PHST- 2013/05/30 00:00 [pmc-release]
AID - PONE-D-13-06007 [pii]
AID - 10.1371/journal.pone.0064329 [doi]
PST - epublish
SO  - PLoS One. 2013 May 30;8(5):e64329. doi: 10.1371/journal.pone.0064329. Print 2013.