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 (ZnSO<inf>4</inf>, 200 μg/kg, i.c.) 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 (2μl) was given to the rats belonging to the control group, Rats in the third group were given ZnSO<inf>4</inf> + 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.