N-nitro-L-arginine methyl ester influence on aluminium toxicity in the brain.

1 , Miodrag Colic 1 , Ankica Jelenkovic 2 , Dubravko Bokonjic 3 , Milica Ninkovic A b s t r a c t We investigated the influence of a non-specific nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on brain nitrite concentration and acetylcholine esterase activity in AlCl 3-treated Wistar rats. Animals were killed 10 min, three hours, three days and 30 days after the treatment and hippocampus and basal forebrain were removed. The biochemical changes observed in neuronal tissues show the involvement of NO in the AlCl 3 toxicity and cholinergic neurotransmission, and that L-NAME may have potential neuroprotective effects. Active avoidance learning was significantly impaired after AlCl 3 application, while pretreatment with L-NAME prevented the behavioural deficits caused by AlCl 3. We also applied immunohistochemical techniques to identify changes induced by AlCl 3, L-NAME+AlCl 3, as well as L-NAME injections after survival periods of three days and 30 days. Immunoreactivity of astrocytes and phagocytic microglia based on glial fibrillary acidic protein (GFAP) and a useful marker for rat macrophages (ED1), respectively, revealed a greater inflammatory response in AlCl 3-injected animals compared to controls.