title: Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity.
abstract: BACKGROUND
  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 (NO(x)) 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.
  
  
  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(2)(•-)), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO(3)(-)) 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 NO(x) and O(2)(•-) 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.
  
  
  CONCLUSIONS
  The i.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.
authors: Department of Toxicology, Faculty of Pharmacy, Belgrade University, Belgrade, Serbia. mirjana.djukic@pharmacy.bg.ac.rs
authors: Mirjana
authors: M
authors: Djukic
authors: Marina D
authors: MD
authors: Jovanovic
authors: Milica
authors: M
authors: Ninkovic
authors: Ivana
authors: I
authors: Stevanovic
authors: Marijana
authors: M
authors: Curcic
authors: Aleksandra
authors: A
authors: Topic
authors: Dragana
authors: D
authors: Vujanovic
authors: Dragan
authors: D
authors: Djurdjevic
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004178:Diquat / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000517:prevention & control*; D009566:Nitrates / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D006540:Herbicides; D009566:Nitrates; D009589:Nitrogen Oxides; D013481:Superoxides; D008315:Malondialdehyde; D004178:Diquat; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester