Neuroprotective effects of Tacrolimus (FK-506) and Cyclosporin (CsA) in oxidative injury

Seema Yousuf, Fahim Atif, Varun Kesherwani, Sandeep Kumar Agrawal

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The detrimental effects of hypoxic damage to central nervous systemlead to energy depletion, free radical formation, lipid peroxidation (LPO), and increased calcium. We hypothesized that in vitro tacrolimus (FK-506) and cyclosporine A (CsA) could be protective against hypoxic damage in spinal cord. Dorsal columns were isolated from the spinal cord of adult rats and injured by exposure to hypoxic condition for 1 h, and treated with FK-506 (0.1 μM) and CsA (0.1 μM). After injury, reperfusion was carried out for 2 h. Tissues were collected, processed for biochemical assays, and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Spinal cord hypoxia caused a significant decrease (P <0.001) in mitochondrial ATP (30.64%) and tissue reduced glutathione (GSH) (60.14%) content. Conversely, a significant increase (P <0.001) in tissue LPO level (57.77%) and myeloperoxidase (MPO) activity (461.24%) was observed in hypoxic group. Mitochondrial swelling was also significantly increased in hypoxic group (90.0%). Treatment with either FK-506 or CsA showed that significant neuroprotective effects (P < 0.05-0.01) were measured in various parameters in hypoxic groups. FK-506 and CsA treatment showed increase in ATP by 11.19% and 16.14% whileGSH content increased by 66.46% and 77.32%, respectively. Conversely, LPO content decreased by 18.97% and 24.06% and MPO level by 42.86% and 18.66% after FK-506 and CsA treatment. Calcium uptake was also decreased in mitochondria as exhibited by the increase in absorbance by 11.19% after FK-506 treatment. TTC staining also showed increased viability after FK-506 and CsA treatment. In conclusion, present study demonstrates the neuroprotective effect of FK-506 and CsA treatment against spinal cord hypoxia induced damage ismediated via their antioxidant actions.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalBrain and Behavior
Issue number2
StatePublished - Nov 2011
Externally publishedYes


  • ATP
  • Hypoxia
  • Mitochondrial swelling
  • Neuroprotection
  • Spinal cord

ASJC Scopus subject areas

  • Behavioral Neuroscience


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