A NOS inhibitor aminoguanidine reduces zinc-induced neuron loss in rat hippocampus

Abstract

There are many studies on zinc as a possible cause of neuronal hyperactivity and cell death. The present study was designed to investigate the changes in total pyramidal cell number of rat hippocampus after intracortical zinc sulphate (ZnSO4, 200 mug/kg, i.e.) and a nitric oxide synthase (NOS) inhibitor aminoguanidine (AG) administration. Animals were divided into three groups as control, zinc and the treatment (zinc+AG) groups. Each group was divided into two subgroups, as 7-day group and 15-day group. Zinc sulphate was injected intracortically into 2 mm lateral of Bregma. The same volume of saline (2 mul) was given to the rats belonging to the control group. Rats in the third group were given ZnSO4 + AG in the same injection point. Animals in the third group only received 100 mg/kg AG intraperitoneally twice a day for periods of 7 or 15 days. Total pyramidal neuron number was estimated using the optical fractionator method. The total number of pyramidal cells found in the left hippocampus was 653,468 +/- 3,452 and 601,860 +/- 3,348 in the control groups; 257,968 +/- 1,277 and 250,555 +/- 1,443 in the zinc groups; 382,519 +/- 1,973 and 365,880 +/- 2,658 in the treatment groups in 7-day post treatment and 15-day post treatment rats, respectively. These results suggest that zinc has a neurotoxic effect on pyramidal neurons in rat hippocampus (p < 0.05) and an inhibitor of nitric oxide synthase, AG, decreases cell loss (p < 0.05). This shows that nitric oxide (NO) contributes to this type of neurotoxicity in the rat hippocampus and also suggests a possible therapeutic role for NOS inhibitor in neurodegenerative diseases.