Agmatine as retinal protection from ischemia-reperfusion injury in guinea pigs.
OBJECTIVE
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 microm) and Agm 2 (24.49 +/- 0.88 microm) groups was lower than that of those in the control 1 (37.60 +/- 2.27 microm) and control 2 (36. 64 +/- 1.32 microm) 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.


CONCLUSIONS
Agmatine exerts a significant neuroprotective effect on guinea pig retinas after transient ischemia-reperfusion insult.
Dastan
Ali
A
Department of Ophthalmology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Kocer
Ibrahim
I
Erdogan
Fazli
F
Ates
Orhan
O
Kiziltunc
Ahmet
A
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D007429:Intraocular Pressure; D015227:Lipid Peroxidation; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D000376:Agmatine; D052248:Nitric Oxide Synthase Type I