PMID- 30783935
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20200225
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 46
IP  - 2
DP  - 2019 Apr
TI  - Colistin induced peripheral neurotoxicity involves mitochondrial dysfunction and 
      oxidative stress in mice.
PG  - 1963-1972
LID - 10.1007/s11033-019-04646-5 [doi]
AB  - Polymyxin is a critical antibiotic against the infection caused by 
      multidrug-resistant gram-negative bacteria. Neurotoxicity is one of main 
      dose-limiting factors. The present study aimed to investigate the underlying 
      molecular mechanism on colistin induced peripheral neurotoxicity using a mouse 
      model. Forty mice were divided into control, colistin 1-, 3- and 7-day groups, 
      the mice were intravenously injected with saline or colistin (sulfate) at the 
      dose of 15 mg/kg/day for 1, 3 and 7 days, respectively. The results showed that, 
      colistin treatment for 7 days markedly resulted in the demyelination, axonal 
      degeneration and mitochondria swelling in the mice's sciatic tissues. Colistin 
      treatment induces oxidative stress as well as the increases of mitochondrial 
      permeability transition, decreases of membrane potential (DeltaPsi(m)) and activities 
      of mitochondrial respiratory chain in the mice's sciatic nerve tissues. 
      Furthermore, in the colistin-7 day group, adenosine-triphosphate (ATP) level 
      Na(+)/K(+)-ATPase activity decreased to 75.2% (p < 0.01) and 80.1% (p < 0.01), 
      respectively. Meanwhile, colistin treatment down-regulates the expression of 
      protein kinase B (Akt) and mammalian target of rapamycin (mTOR) mRNAs and 
      up-regulates the expression of Bax and caspase-3 mRNAs. Our results reveal that 
      colistin induced sciatic nerves damage involves oxidative stress, mitochondrial 
      dysfunction and the inhibition of Akt/mTOR pathway.
FAU - Dai, Chongshan
AU  - Dai C
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, People's Republic of China.
AD  - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, 
      People's Republic of China.
FAU - Tang, Shusheng
AU  - Tang S
AD  - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, 
      People's Republic of China.
FAU - Biao, Xiang
AU  - Biao X
AD  - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, 
      People's Republic of China.
FAU - Xiao, Xilong
AU  - Xiao X
AD  - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, 
      People's Republic of China.
FAU - Chen, Chunli
AU  - Chen C
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, People's Republic of China. chunli.chen@neau.edu.cn.
FAU - Li, Jichang
AU  - Li J
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, People's Republic of China. lijichang@neau.edu.cn.
LA  - eng
GR  - 31472240/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190219
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 0 (Reactive Oxygen Species)
RN  - Z67X93HJG1 (Colistin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - China
MH  - Colistin/*metabolism/*pharmacology/toxicity
MH  - Female
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Oxidative Stress/drug effects/physiology
MH  - Peripheral Nervous System Diseases/chemically induced/*physiopathology
MH  - Reactive Oxygen Species/metabolism
MH  - Sciatic Neuropathy/chemically induced/physiopathology
OTO - NOTNLM
OT  - Akt/mTOR pathway
OT  - Colistin
OT  - Mitochondrial dysfunction
OT  - Oxidative stress
OT  - Peripheral neurotoxicity
EDAT- 2019/02/21 06:00
MHDA- 2019/09/11 06:00
CRDT- 2019/02/21 06:00
PHST- 2018/11/30 00:00 [received]
PHST- 2019/01/24 00:00 [accepted]
PHST- 2019/02/21 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2019/02/21 06:00 [entrez]
AID - 10.1007/s11033-019-04646-5 [pii]
AID - 10.1007/s11033-019-04646-5 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2019 Apr;46(2):1963-1972. doi: 10.1007/s11033-019-04646-5. Epub 
      2019 Feb 19.