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

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2012
Intrastriatal_pre_treatment_pub_2012.pdf (218.6Kb)
Authors
Đukić, Mirjana
Jovanović, Marina
Ninković, Milica
Stevanović, Ivana
Ćurčić, Marijana
Topić, Aleksandra
Vujanović, Dragana
Đurđević, Dragan
Article (Published version)
Metadata
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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.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
Publisher:
  • 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).

ISSN: 1232-1966

PubMed: 23311786

WoS: 000313298600011

Scopus: 2-s2.0-84871589433
[ Google Scholar ]
11
13
Handle
https://hdl.handle.net/21.15107/rcub_farfar_1663
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1663
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Đukić, Mirjana
AU  - Jovanović, Marina
AU  - Ninković, Milica
AU  - Stevanović, Ivana
AU  - Ćurčić, Marijana
AU  - Topić, Aleksandra
AU  - Vujanović, Dragana
AU  - Đurđević, Dragan
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1663
AB  - 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.
PB  - Inst Agricultural Medicine, Lublin
T2  - Annals of Agricultural and Environmental Medicine
T1  - Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity
VL  - 19
IS  - 4
SP  - 666
EP  - 672
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1663
ER  - 
@article{
author = "Đukić, Mirjana and Jovanović, Marina and Ninković, Milica and Stevanović, Ivana and Ćurčić, Marijana and Topić, Aleksandra and Vujanović, Dragana and Đurđević, Dragan",
year = "2012",
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.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.",
publisher = "Inst Agricultural Medicine, Lublin",
journal = "Annals of Agricultural and Environmental Medicine",
title = "Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity",
volume = "19",
number = "4",
pages = "666-672",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1663"
}
Đukić, M., Jovanović, M., Ninković, M., Stevanović, I., Ćurčić, M., Topić, A., Vujanović, D.,& Đurđević, D.. (2012). Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity. in Annals of Agricultural and Environmental Medicine
Inst Agricultural Medicine, Lublin., 19(4), 666-672.
https://hdl.handle.net/21.15107/rcub_farfar_1663
Đukić M, Jovanović M, Ninković M, Stevanović I, Ćurčić M, Topić A, Vujanović D, Đurđević D. Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity. in Annals of Agricultural and Environmental Medicine. 2012;19(4):666-672.
https://hdl.handle.net/21.15107/rcub_farfar_1663 .
Đukić, Mirjana, Jovanović, Marina, Ninković, Milica, Stevanović, Ivana, Ćurčić, Marijana, Topić, Aleksandra, Vujanović, Dragana, Đurđević, Dragan, "Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity" in Annals of Agricultural and Environmental Medicine, 19, no. 4 (2012):666-672,
https://hdl.handle.net/21.15107/rcub_farfar_1663 .

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