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

Mirjana Djukic 1, Marina D Jovanovic 2, Milica Ninkovic 2, Ivana Stevanovic 2, Marijana Curcic 1, Aleksandra Topic 3, Dragana Vujanovic 1, Dragan Djurdjevic 2
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):
ICID: 1024067
Article type: Original article
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.s.) administration and to investigate the role of nitric oxide (NOx) using NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of DQ i.s. 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 (O2• ˉ), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO3ˉ) were measured in the cortex (bilaterally), at 30 th 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 NOx and O2• 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.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.
PMID 23311786 - click here to show this article in PubMed

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