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RESEARCH PAPER
 
 

Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity

 
1
Department of Toxicology, Faculty of Pharmacy, Belgrade University, Serbia
2
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
3
Department of Biochemistry, Faculty of Pharmacy, Belgrade University, Serbia
Ann Agric Environ Med 2012;19(4):666–672
KEYWORDS:
ABSTRACT:
Introduction: Contact herbicide diquat (DQ), redox cycling compound, mediates its systemic toxicity throughout the enlarged production of free radicals. Target organs are liver and kidney in humans. To-date, the mechanism of DQ-induced neurotoxicity has not been rationalized. Objective: The objectives of the study were to examine the ability of DQ to induce oxidative stress (OS) and/or nitrosative stress (NS) upon intrastriatal ([i]i.s.[/i]) administration and to investigate the role of nitric oxide (NO[sub]x[/sub]) using NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of DQ [i]i.s[/i]. administration. Material and Methods: The experiment was conducted on Wistar rats, randomly divided in experimental groups, receiving different treatments i.s. applied. Parameters of OS/NS such as: superoxide anion radical (O[sub]2[/sub]• ˉ), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO[sub]3[/sub]ˉ) were measured in the cortex (bilaterally), at 30 [sup]th[/sup] min, 24 hours and 7 days after the treatments. Results: Lethargy and high mortality rate were observed only in the DQ group (within 24 hours and 2-3 hours, respectively) after awakening from anesthesia. Markedly increased production of NO[sub]x[/sub] and O[sub]2[/sub]• ˉ along with elevated lipid peroxidation altogether contributed to DQ neurotoxicity. The most importantly, the L-NAME i.s. pretreatment protected treated animals from dying and diminished OS/NS response against DQ-induced neurotoxicity. Conclusion: The[i] i.s.[/i] pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.
eISSN:1898-2263
ISSN:1232-1966