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Agmatine as retinal protection from ischemia-reperfusion injury in guinea pigs

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To determine the neuroprotective effect of agmatine (Agm) on the retinas of guinea pigs subjected to a transient ischemia-reperfusion insult.

Methods

Twenty-eight guinea pigs were randomly divided into four groups. Forty-five minutes before ischemic insult, the guinea pigs were intraperitoneally administered either Agm (50 mg/kg) (Agm 1) or saline (control 1 group) once, or twice separated by a 12-h interval (Agm 2; control 2). Transient ocular ischemia was achieved under general anesthesia by cannulating an anterior chamber maintainer connected to an infusion line of a semiflexible bottle. The saline reservoir pressure was increased by using a blood pressure tolls cuff to achieve an intraocular pressure (IOP) of 150 mmHg. This IOP was maintained for 90 min. Reperfusion was achieved by pulling off the anterior chamber maintainer. The animals in the Agm 1 and control 1 groups were killed at the end of the 4-h reperfusion period. The eyes were enucleated for histopathological (retinal thickness) and biochemical (thiobarbituric acid reactive substance, TBARS, and nitric oxide, NO) investigation. The animals in the Agm 2 and control 2 groups were killed at the end of a 24-h reperfusion period.

Results

The mean retinal thickness of the animals in the Agm 1 (25.94 ± 1.23 μm) and Agm 2 (24.49 ± 0.88 μm) groups was lower than that of those in the control 1 (37.60 ± 2.27 μm) and control 2 (36. 64 ± 1.32 μm) groups (P < 0.05). The mean TBARS level of the animals in the Agm 1 (8.37 ± 0.94 nmol/ml) and Agm 2 (8.01 ± 0.97 nmol/ml) groups was lower than that of those in the control 1 (12.09 ± 1.27 nmol/ml) and control 2 (12.09 ± 1.27 and 11.72 ± 1.63 nmol/ml) groups (P < 0.05). The mean NO level of the animals in the Agm 1 (100.77 ± 6.20 nmol/ml) and Agm 2 (94.63 ± 5.24 nmol/ml) was lower than that of those in the control 1 (131.77 ± 4.61 nmol/ml) and control 2 (122.43 ± 4.35 nmol/ml) groups (P < 0.05). There were positive correlations between the TBARS and NO levels and retinal thickness in the Agm and control groups.

Conclusion

Agmatine exerts a significant neuroprotective effect on guinea pig retinas after transient ischemia-reperfusion insult.

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References

  1. Reis DJ, Regunathan S. Is agmatine a novel neurotransmitter in brain? Trends Pharmacol Sci 2000;21:187–193.

    Article  CAS  PubMed  Google Scholar 

  2. Grillo MA, Colombatto S. Metabolism and function in animal tissues of agmatine, a biogenic amine formed from arginine. Amino Acids 2004;26:3–8.

    Article  CAS  PubMed  Google Scholar 

  3. Moinard C, Cynober L, de Bandt JP. Polyamines: metabolism and implications in human diseases. Clin Nutr 2005;24:184–197.

    Article  CAS  PubMed  Google Scholar 

  4. Lortie MJ, Novotny WF, Peterson OW, et al. Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat. J Clin Invest 1996;97:413–420.

    Article  CAS  PubMed  Google Scholar 

  5. Wang WP, Iyo AH, Miguel-Hidalgo J, Regunathan S, Zhu MY. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons Brain Res 2006;108:210–216.

    Article  Google Scholar 

  6. Raasch W, Schäfer U, Chun J, Dominiak P. Biological significance of agmatine, an endogenous ligand at imidazoline binding sites. Br J Pharmacol 2001;133:755–780.

    Article  CAS  PubMed  Google Scholar 

  7. Halaris A, Plietz J. Agmatine: metabolic pathway and spectrum of activity in brain. CNS Drugs. 2007;21:885–900.

    Article  CAS  PubMed  Google Scholar 

  8. Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ. Agmatine an endogenous clonidine-displacing substance in the brain. Science 1994;263:966–969.

    Article  CAS  PubMed  Google Scholar 

  9. Satriano J, Isome M, Casero RA Jr, Thomson SC, Blantz RC. Polyamine transport system mediates agmatine transport in mammalian cells. Am J Physiol Cell Physiol 2001;281:329–334.

    Google Scholar 

  10. Piletz JE, May PJ, Wang G, Zhu H. Agmatine crosses the blood-brain barrier. Ann N Y Acad Sci 2003;1009:64–74.

    Article  CAS  PubMed  Google Scholar 

  11. Lafuente MP, Villegas-Pérez MP, Sellés-Navarro I, Mayor-Torroglosa S, Miralles de Imperial J, Vidal-Sanz M. Retinal ganglion cell death after acute retinal ischemia is an ongoing process whose severity and duration depends on the duration of the insult. Neuroscience 2002;109:157–168.

    Article  CAS  PubMed  Google Scholar 

  12. Nayak MS, Kita M, Marmor MF. Protection of rabbit retina from ischemic injury by superoxide dismutase and catalase. Invest Ophthalmol Vis Sci 1993;34:2018–2022.

    CAS  PubMed  Google Scholar 

  13. Siu AW, Reiter RJ, To CH. Pineal indoleamines and vitamin E reduce nitric oxide-induced lipid peroxidation in rat retinal homogenates. J Pineal Res 1999;27:122–128.

    Article  CAS  PubMed  Google Scholar 

  14. Uchiyama M, Mihara M. Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Ann Biochem 1978;86:271–278.

    Article  CAS  Google Scholar 

  15. Wei Y, Wang N, Lu Q, Zhang N, Zheng D, Li J. Enhanced protein expressions of sortilin and p75NTR in retina of rat following elevated intraocular pressure-induced retinal ischemia. Neurosci Lett 2007;18:169–174.

    Article  Google Scholar 

  16. Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies, Prog Retin Eye Res 2004;23:91–147.

    Article  CAS  PubMed  Google Scholar 

  17. Grozdanic SD, Sakaguchi DS, Kwon YH, Kardon RH, Sonea IM. Functional characterization of retina and optic nerve after acute ocular ischemia in rats. Invest Ophthalmol Vis Sci 2003;44:2597–2605.

    Article  PubMed  Google Scholar 

  18. Riazi-Esfahani M, Kiumehr S, Asadi-Amoli F, Lashay AR, Dehpour AR. Morphine pretreatment provides histologic protection against ischemia-reperfusion injury in rabbit retina. Retina 2008;28:511–517.

    Article  PubMed  Google Scholar 

  19. Adachi M, Takahashi K, Nishikawa M, Miki H, Uyama M. High intraocular pressure-induced ischemia and reperfusion injury in the optic nerve and retina in rats. Graefes Arch Clin Exp Ophthalmol 1996;234:445–451.

    Article  CAS  PubMed  Google Scholar 

  20. Weber M, Mohand-Said S, Hicks D, Dreyfus H, Sahel JA. Monosialoganglioside GM1 reduces ischemia-reperfusion-induced injury in the rat retina. Invest Ophthalmol Vis Sci 1996;37:267–273.

    CAS  PubMed  Google Scholar 

  21. Szabo EM, Droy-Lefaix MT, Doly M, Carre C, Braquer P. Ischemia and reperfusion-induced histologic changes in the rat retina. Invest Ophthalmol Vis Sci 1991;32:1471–1478.

    CAS  PubMed  Google Scholar 

  22. Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978;90:37–43.

    Article  CAS  PubMed  Google Scholar 

  23. Bradford MM. A rapid and sensitive method for the quantization of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem 1976;72:248–254.

    Article  CAS  PubMed  Google Scholar 

  24. Louzada-Junior P, Dias JJ, Santos WF, Lachat JJ, Bradford HF, Coutinho-Netto J. Glutamate release in experimental ischemia of retina: an approach using microdialysis. J Neurochem 1992;59:358–363.

    Article  CAS  PubMed  Google Scholar 

  25. Kageyama T, Ishikawa A, Tamai M. Glutamate elevation in rabbit vitreous during transient ischemia-reperfusion. Jpn J Ophthalmol 2000;44:110–114.

    Article  CAS  PubMed  Google Scholar 

  26. Naskar R, Dreyer EB. New horizons in neuroprotection. Surv Ophthalmol 2001;45 Suppl 3:S250–S255.

    Article  Google Scholar 

  27. White BC, Sullivan JM, DeGracia DJ, et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 2000;179:1–33.

    Article  CAS  PubMed  Google Scholar 

  28. Hong S, Lee JE, Kim CY, Seong GJ. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line. BMC Neurosci 2007;8:81.

    Article  PubMed  Google Scholar 

  29. Kim JH, Yenari MA, Giffard RG, Cho SW, Park KA, Lee JE. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Exp Neurol 2004;189:122–130.

    Article  CAS  PubMed  Google Scholar 

  30. Kim DJ, Kim DI, Lee SK, et al. Protective effect of agmatine on a reperfusion model after transient cerebral ischemia: temporal evolution on perfusion MR imaging and histopathologic findings. Am J Neuroradiol 2006;27:780–785.

    CAS  PubMed  Google Scholar 

  31. Wheeler LA, Gil DW, WoldeMussie E. Role of alpha-2 adrenergic receptors in neuroprotection and glaucoma. Surv Ophthalmol 2001;45Suppl 3:S290–294.

    Article  PubMed  Google Scholar 

Download references

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Correspondence to Ibrahim Kocer.

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Dastan, A., Kocer, I., Erdogan, F. et al. Agmatine as retinal protection from ischemia-reperfusion injury in guinea pigs. Jpn J Ophthalmol 53, 219–224 (2009). https://doi.org/10.1007/s10384-009-0660-0

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  • DOI: https://doi.org/10.1007/s10384-009-0660-0

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