Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity
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Department of Toxicology, Faculty of Pharmacy, Belgrade University, Serbia
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
Department of Biochemistry, Faculty of Pharmacy, Belgrade University, Serbia
Mirjana Djukic   

Department of Toxicology, Faculty of Pharmacy, Belgrade University, Serbia
Ann Agric Environ Med. 2012;19(4):666–672
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.

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 30th min, 24 hours and 7 days after the treatments.

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.

The i.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.

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