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Molecular Biology Reports

, Volume 46, Issue 2, pp 1963–1972 | Cite as

Colistin induced peripheral neurotoxicity involves mitochondrial dysfunction and oxidative stress in mice

  • Chongshan Dai
  • Shusheng Tang
  • Xiang Biao
  • Xilong Xiao
  • Chunli ChenEmail author
  • Jichang LiEmail author
Original Article
  • 102 Downloads

Abstract

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 (ΔΨm) 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.

Keywords

Colistin Peripheral neurotoxicity Oxidative stress Mitochondrial dysfunction Akt/mTOR pathway 

Notes

Acknowledgements

This study is supported by National Natural Science Foundation of China (Grant Nos. 31472240 and 31802241 To J.L.and C. C.; C. D, S.T. and X.X. was supported by the Key Projects in Chinese National Science and Technology Pillar Program during the 12th Five-year Plan Period, No. 2015BAD11B03).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.College of Veterinary MedicineNortheast Agricultural UniversityHarbinPeople’s Republic of China
  2. 2.College of Veterinary MedicineChina Agricultural UniversityBeijingPeople’s Republic of China

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