Cyclooxygenase inhibition attenuates 3‐nitropropionic acid‐induced neurotoxicity in rats: possible antioxidant mechanisms

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.

Effects of caffeic acid, rofecoxib, and their combination against quinolinic acid-induced behavioral alterations and disruption in glutathione redox status

“…Further, caffeic acid and rofecoxib treatment could significantly revert these glutathione alterations in the QA-treated animals, restoring the reduction in glutathione level and redox ratio, and attenuating the increase of oxidized glutathione level. Moreover, combination of rofecoxib and caffeic acid strengthened the protective effect, which is also consistent with previous findings that COX, LOX and dual inhibitors could exert neuroprotective effect at different neurodegenerative conditions [19,29,57] .…”

“…Furthermore, co-treatment of caffeic acid and rofecoxib ex- Also, the neuroprotective-and antioxidative-like actions of the selective inhibitors for LOX and COX-2 have been well documented [19,29] .…”

“…Consistent with earlier reports, our study suggests that intrastriatal QA injection induces motor incoordination, which may be due to the degeneration of striatal neurons. Antioxidative and protective effects of COX and LOX inhibitors have been well documented in various neurodegenerative conditions [19,29] . In the present study, both caffeic acid and rofecoxib significantly attenuated the behavioral alterations in QA-treated rats.…”

“…Animals were placed individually in the activity chamber for 3 min as a habituation period before the 5-min motor activity task. Total activity (horizontal and vertical) was expressed as counts per 5 min as described by Kumar [19] .…”

Conotoxins: Possible Therapeutic Measure for Huntingtons Disease

“…Animals were placed individually in the activity chamber for 3min as a habituation period before making actual recording. Each animal was observed over a period of 5min and expressed as counts per 5min [30].…”