Research Article

Effects of Tacrolimus on Endothelin-1, Melatonin and Heat Shock Protein Levels in Experimental Brain Ischemia

Volume: 14 Number: 2 July 15, 2019
Özlem Güler *, Mustafa Yıldız , Mehmet Nuri Bozdemir , Ahmet Kavaklı , Adile Ferda Dağlı , Bilal Üstündağ
EN TR

Effects of Tacrolimus on Endothelin-1, Melatonin and Heat Shock Protein Levels in Experimental Brain Ischemia

Abstract

Objective: We aimed to investigate the effects of tacrolimus on plasma endothelin-1, melatonin and brain Hsp-70 levels in experimental ischemic stroke in this study.

Material and Methods: Twenty-one male Wistar-Albino rats randomly divided into three groups which included seven rats. Animals in group 2 and group 3 were anesthetized and bilateral common carotid arteries were clamped with aneurysm clips for 10 minutes. Animals in group 1 were not clamped and were not given any treatment. Rats in group 2 were received 1 ml saline and in group 3 were received 1 mg/kg tacrolimus intraperitoneally. Injections were applied 1st hour before ischemia and at 6th, 24th, 48th and 72nd hours post ischemia. All the animals were decapitated on the 4th day and plasmas were obtained and brains were excised. Plasma endothelin-1 and melatonin levels were measured. Brain Hsp-70 immunostaining and neuron cell death were scored semiquantitatively.

Results: The plasma endothelin-1 levels in group 3 were higher than group 2 and group 1, but were similar in group 1 and group 2.  In group 1 plasma melatonin levels were lesser than group 2 and group 3. In group 2 plasma melatonin levels were higher than group 3. The mean neuron death in group 3 was lesser than in group 2. The mean Hsp-70 immunostaining intensity in group 2 was greater than group 3 and group 1. In group 1 the mean Hsp-70 immünostaining intensity was lesser than group 3.

Conclusions: Tacrolimus administration in ischemic stroke reduces plasma melatonin and brain Hsp-70 levels and increases plasma endothelin-1 levels and has neuroprotective effect.

Keywords

Endothelin-1,Heat Shock Protein-70,ischemic stroke,melatonin,tacrolimus

References

  1. 1. Ginsberg MD. Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 2008; 55: 363-89.
  2. 2. Shuaib A, Hussain MS. The past and future of neuroprotection in cerebral ischaemic stroke. Eur Neurol 2008; 59: 4-14.
  3. 3. Patury S, Miyata Y, Gestwicki JE. Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 2009; 9: 1337-51.
  4. 4. Abraham D, Dashwood M. Endothelin--role in vascular disease. Rheumatology (Oxford) 2008; 47: v23-24.
  5. 5. Esposito E, Cuzzocrea S. Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol 2010; 8: 228-42.
  6. 6. Reiter RJ. Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 1998; 56: 359-84.
  7. 7. Almawi WY, Melemedjian OK. Clinical and mechanistic differences between FK506 (tacrolimus) and cyclosporin A. Nephrol Dial Transplant 2000; 15: 1916-18.
  8. 8. Sharkey J, Crawford JH, Butcher SP, Marston HM. Tacrolimus (FK506) ameliorates skilled motor deficits produced by middle cerebral artery occlusion in rats. Stroke 1996;27:2282-6.
  9. 9. Zawadzka M, Kaminska B. A novel mechanism of FK506-mediated neuroprotection: downregulation of cytokine expression in glial cells. Glia 2005; 49: 36-51.
  10. 10. Cho S, Liu D, Gonzales C, Zaleska MM, Wood A. Temporal assessment of caspase activation in experimental models of focal and global ischemia. Brain Res 2003; 982: 146-55.
AMA
1.Güler Ö, Yıldız M, Bozdemir MN, Kavaklı A, Dağlı AF, Üstündağ B. Effects of Tacrolimus on Endothelin-1, Melatonin and Heat Shock Protein Levels in Experimental Brain Ischemia. KSU Medical Journal. 2019;14(2):75-79. doi:10.17517/ksutfd.533419