Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity
Article (Published version)
MetadataShow full item record
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 (O-2(center dot-)), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO3-) were measured in the cortex (bilaterally), at ...30th 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 O-2(center dot-) 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.
Keywords:diquat / oxidative stress / nitric oxide / L-NAME / Wistar rats / brain
Source:Annals of Agricultural and Environmental Medicine, 2012, 19, 4, 666-672
- Inst Agricultural Medicine, Lublin
Funding / projects:
- Preventive, therapeutic, and ethical approach in preclinical and clinical studies of the genes and modulators of redox cell signaling in immune, inflammatory and proliferative cell response (RS-41018)
- Complex diseases as a model system for phenotype modulation- structural and functional analysis of molecular biomarkers (RS-173008)
- Ministry of Defense of the Republic of Serbia (Project No. MMA/06-10/B.3).