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Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms.
Fundam Clin Pharmacol. 2007 Jun; 21(3):297-306.FC

Abstract

Systemic administration of 3-nitropropionic acid (3-NP), a complex II inhibitor of the electron transport chain, causes motor and cognitive deficits that are associated with excitotoxicity and excessive free radical generation. Recently, cyclooxygenase (COX) inhibitors have been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate the effects of COX inhibitors in 3-NP-induced cognitive impairment and oxidative stress in rats. Intraperitoneal administration of 3-NP (20 mg/kg for 4 days) showed motor abnormalities and cognitive impairment in rats. Chronic treatment with naproxen (10 and 20 mg/kg) and valdecoxib (5 and 10 mg/kg) once daily for a period of 8 days beginning 4 days prior to 3-NP administration significantly improved 3-NP-induced motor and cognitive impairment in rats. Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and nitrite levels, depleted reduced glutathione levels and reduced succinate dehydrogenase (SDH) activity in the brains of rats, whereas administration of naproxen, a nonselective COX inhibitor (10 and 20 mg/kg p.o.) and valdecoxib, a selective COX-2 inhibitor (5 and 10 mg/kg p.o.) significantly attenuated 3-NP-induced oxidative stress. Cyclooxygenase inhibitors also significantly restored the decreased SDH activity. The results of the present study clearly indicate that naproxen and valdecoxib showed protection against 3-NP-induced motor and cognitive impairment by decreasing oxidative stress.

Authors+Show Affiliations

Kumar P
Pharmacology Division, University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh 160014, India.
Padi SS
No affiliation info available
Naidu PS
No affiliation info available
Kumar A
No affiliation info available

MeSH

AnimalsBehavior, AnimalBrainCyclooxygenase InhibitorsGlutathioneIsoxazolesLipid PeroxidationMaleMalondialdehydeMaze LearningMemoryMotor ActivityNaproxenNeuroprotective AgentsNeurotoxicity SyndromesNitritesNitro CompoundsOxidative StressPropionatesRatsRats, WistarSuccinate DehydrogenaseSulfonamides

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17521299

Citation

Kumar, P, et al. "Cyclooxygenase Inhibition Attenuates 3-nitropropionic Acid-induced Neurotoxicity in Rats: Possible Antioxidant Mechanisms." Fundamental & Clinical Pharmacology, vol. 21, no. 3, 2007, pp. 297-306.
Kumar P, Padi SS, Naidu PS, et al. Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms. Fundam Clin Pharmacol. 2007;21(3):297-306.
Kumar, P., Padi, S. S., Naidu, P. S., & Kumar, A. (2007). Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms. Fundamental & Clinical Pharmacology, 21(3), 297-306.
Kumar P, et al. Cyclooxygenase Inhibition Attenuates 3-nitropropionic Acid-induced Neurotoxicity in Rats: Possible Antioxidant Mechanisms. Fundam Clin Pharmacol. 2007;21(3):297-306. PubMed PMID: 17521299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms. AU - Kumar,P, AU - Padi,S S V, AU - Naidu,P S, AU - Kumar,A, PY - 2007/5/25/pubmed PY - 2007/8/22/medline PY - 2007/5/25/entrez SP - 297 EP - 306 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 21 IS - 3 N2 - Systemic administration of 3-nitropropionic acid (3-NP), a complex II inhibitor of the electron transport chain, causes motor and cognitive deficits that are associated with excitotoxicity and excessive free radical generation. Recently, cyclooxygenase (COX) inhibitors have been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate the effects of COX inhibitors in 3-NP-induced cognitive impairment and oxidative stress in rats. Intraperitoneal administration of 3-NP (20 mg/kg for 4 days) showed motor abnormalities and cognitive impairment in rats. Chronic treatment with naproxen (10 and 20 mg/kg) and valdecoxib (5 and 10 mg/kg) once daily for a period of 8 days beginning 4 days prior to 3-NP administration significantly improved 3-NP-induced motor and cognitive impairment in rats. Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and nitrite levels, depleted reduced glutathione levels and reduced succinate dehydrogenase (SDH) activity in the brains of rats, whereas administration of naproxen, a nonselective COX inhibitor (10 and 20 mg/kg p.o.) and valdecoxib, a selective COX-2 inhibitor (5 and 10 mg/kg p.o.) significantly attenuated 3-NP-induced oxidative stress. Cyclooxygenase inhibitors also significantly restored the decreased SDH activity. The results of the present study clearly indicate that naproxen and valdecoxib showed protection against 3-NP-induced motor and cognitive impairment by decreasing oxidative stress. SN - 0767-3981 UR - https://www.unboundmedicine.com/medline/citation/17521299/Cyclooxygenase_inhibition_attenuates_3_nitropropionic_acid_induced_neurotoxicity_in_rats:_possible_antioxidant_mechanisms_ DB - PRIME DP - Unbound Medicine ER -