Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity
Journal Title: Annals of Agricultural and Environmental Medicine - Year 2012, Vol 19, Issue 4
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.
Authors and Affiliations
Mirjana Djukic, Marina Jovanovic, Milica Ninkovic, Ivana Stevanovic, Marijana Curcic, Aleksandra Topic, Dragana Vujanovic, Dragan Djurdjevic
Keywords
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