Effects of L-NAME, a non-specific nitric oxide synthase inhibitor, on AlCl3-induced toxicity in the rat forebrain cortex.
The present experiments were done to determine the effectiveness of a non-specific nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on oxidative stress parameters induced by aluminium chloride (AlCl(3)) intrahippocampal injections in Wistar rats. Animals were sacrificed 3 h and 30 d after treatments, heads were immediately frozen in liquid nitrogen and forebrain cortices were removed. Crude mitochondrial fraction preparations of forebrain cortices were used for the biochemical analyses: nitrite levels, superoxide production, malondialdehyde concentrations, superoxide dismutase (SOD) activities and reduced glutathione contents. AlCl(3) injection resulted in increased nitrite concentrations, superoxide anion production, malondialdehyde concentrations and reduced glutathione contents in the forebrain cortex, suggesting that AlCl(3) exposure promoted oxidative stress in this brain structure. The biochemical changes observed in neuronal tissues showed that aluminium acted as a pro-oxidant. However, the nonspecific nitric oxide synthase (NOS) inhibitor, L-NAME, exerted anti-oxidant actions in AlCl(3)-treated animals. These results revealed that NO-mediated neurotoxicity due to intrahippocampal AlCl3 injection spread temporally and spatially to the forebrain cortex, and suggested a potentially neuroprotective effect for L-NAME.
Stevanović
Ivana D
ID
Military Medical Academy, Institute for Medical Research, Crnotravska 17, Belgrade, Serbia. ivanav13@yahoo.ca
Jovanović
Marina D
MD
Jelenković
Ankica
A
Colić
Miodrag
M
Stojanović
Ivana
I
Ninković
Milica
M
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000818:Animals; D002712:Chlorides / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D017607:Aluminum Compounds; D002712:Chlorides; D009573:Nitrites; D013481:Superoxides; D000077410:Aluminum Chloride; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester