J Vet Sci.  2009 Mar;10(1):15-22. 10.4142/jvs.2009.10.1.15.

Effects of L-NAME, a non-specific nitric oxide synthase inhibitor, on AlCl3-induced toxicity in the rat forebrain cortex

Affiliations
  • 1Military Medical Academy, Institute for Medical Research, Crnotravska 17, Belgrade, Serbia. ivanav13@yahoo.ca
  • 2Institute for Biological Research, Belgrade, Serbia.
  • 3Department of Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia.

Abstract

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 (AlCl3) 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. AlCl3 injection resulted in increased nitrite concentrations, superoxide anion production, malondialdehyde concentrations and reduced glutathione contents in the forebrain cortex, suggesting that AlCl3 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 non-specific nitric oxide synthase (NOS) inhibitor, L-NAME, exerted anti-oxidant actions in AlCl3-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.

Keyword

aluminium chloride; forebrain cortex; L-NAME; nitric oxide; oxidative stress

MeSH Terms

Aluminum Compounds/*toxicity
Animals
Chlorides/*toxicity
Glutathione/metabolism
Male
Malondialdehyde
NG-Nitroarginine Methyl Ester/*pharmacology
Nitric Oxide Synthase/*antagonists & inhibitors
Nitrites/chemistry/metabolism
Prosencephalon/*drug effects
Rats
Rats, Wistar
Superoxide Dismutase/metabolism
Superoxides/metabolism

Figure

  • Fig. 1 The effects of intrahippocampal drug injection on nitrite levels (nM nitrite/mg protein) in the rat ipsilateral and contralateral forebrain cortex at different survival times: 3 h (A) and 30 d (B). Results are means ± SD of 10 animals. *Indicates a statistically significant difference between treated (AlCl3-, L-NAME + AlCl3- and L-NAME-treated) and control (sham-operated) animals (p < 0.05). •Indicates a statistically significant difference between treated (L-NAME + AlCl3- and L-NAME-treated) and AlCl3-treated animals (p < 0.05). ♦Indicates a statistically significant difference between L-NAME-treated and L-NAME + AlCl3-treated animals (p < 0.05).

  • Fig. 2 The effects of intrahippocampal drug injection on ·O2- levels (µM red. NBT/min/mg proteins) in the rat ipsilateral and contralateral forebrain cortex at different survival times: 3 h (A) and 30 d (B). Results are means ± SD of 10 animals. *Indicates a statistically significant difference between treated (AlCl3-, L-NAME + AlCl3- and L-NAME-treated) and control (sham-operated) animals (p < 0.05). •Indicates a statistically significant difference between treated (L-NAME + AlCl3- and L-NAME-treated) and AlCl3-treated animals (p < 0.05).

  • Fig. 3 The effects of intrahippocampal drug injection on lipide peroxidation (nM MDA/h/mg proteins) in the rat ipsilateral and contralateral forebrain cortex at different survival times: 3 h (A) and 30 d (B). Results are means ± SD of 10 animals. *Indicates a statistically significant difference between treated (AlCl3- and L-NAME-treated) and control (sham-operated) animal (p < 0.05). •Indicates a statistically significant difference between treated (L-NAME + AlCl3- and L-NAME-treated) and AlCl3-treated animals (p < 0.05). ♦Indicates a statistically significant difference between L-NAME-treated and L-NAME + AlCl3-treated animals (p < 0.05).

  • Fig. 4 The effects of intrahippocampal drug injection on SOD activities (U/mg proteins) in the rat ipsilateral and contralateral forebrain cortex at different survival times: 3 h (A) and 30 d (B). Results are means ± SD of 10 animals. *Indicates a statistically significant difference between treated (L-NAME + AlCl3- and L-NAME-treated) and control (sham-operated) animal (p < 0.05). •Indicates a statistically significant difference between treated (L-NAME + AlCl3- and L-NAME-treated) and AlCl3-treated animals (p < 0.05). ♦Indicates a statistically significant difference between L-NAME-treated and L-NAME + AlCl3-treated animals (p < 0.05).

  • Fig. 5 The effects of intrahippocampal drug injection on reduced glutathione concentrations (nM GSH/mg proteins) in the rat ipsilateral and contralateral forebrain cortex at different survival times: 3 h (A) and 30 d (B). Results are means ± SD of 10 animals. *Indicates a statistically significant difference between treated (AlCl3-, L-NAME + AlCl3- and L-NAME-treated) and control (sham-operated) animals (p < 0.05). •Indicates a statistically significant difference between treated (L-NAME + AlCl3- and L-NAME-treated) and AlCl3-treated animals (p < 0.05). ♦Indicates a statistically significant difference between L-NAME-treated and L-NAME + AlCl3-treated animals (p < 0.05).


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