Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats

Abstract

Oxidative stress has long been implicated in the neurotoxic effects of glutamate acting through N-methyl-D-aspartate (NMDA) receptors. Therefore, present study has been designed to explore the effect of rofecoxib and caffeic acid on the involvement of oxidative stress, mitochondrial dysfunction and neuronal linked with NMDA receptor-mediated excitotoxicity. Caffeic acid, is a well-known antioxidant flavanoid, implicate anti-inflammatory and immunomodulatory like actions. The present study is an attempt to investigate the antioxidant-like effect of caffeic acid and rofecoxib and their combination against QA-induced oxidative damage, mitochondrial dysfunction and histological alterations. Intrastriatal injection of quinolinic acid (300 nmol) significantly increased oxidative stress (raised lipid peroxidation, nitrite concentration, depleted SOD and catalase), altered mitochondrial complex enzyme activities and histological alteration in the ex vivo striatum. Caffeic acid (5 and 10 mg/kg, p.o.) and rofecoxib (10 and 20 mg/kg, p.o.) treatment for 21 days significantly attenuated oxidative damage and impairment in mitochondrial activities of complex enzymes in the ex vivo striatum. Further, combination of sub effective doses of rofecoxib (10 mg/kg, p.o.) and caffeic acid (5 mg/kg, p.o.) potentiated their protective effect which was significant as compared to their effect per se. The present study suggests the therapeutic effect of caffeic acid and rofecoxib combination against QA-induced ex vivo oxidative damage, mitochondrial and histological alterations in rats.

Caffeic Acid Phenethyl Ester Protects Blood–Brain Barrier Integrity and Reduces Contusion Volume in Rodent Models of Traumatic Brain Injury

“…For example, CAPE/caffeic acid has been reported to protect the brain against induced diabetes, quinolinic acid-induced brain damage, aluminuminduced toxicity, neonatal hypoxia, and transient focal ischemia (Celik and Erdogan, 2008;Kalonia et al, 2009;Khan et al, 2007;Wei et al, 2004;Yang et al, 2008;Zhou et al, 2006). Caffeic acid has also been reported to reduce lesion area and glial scar formation following cryoinjury in mice (Zhang et al, 2007).…”

Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide

“…These enzymes are involved in initiation, maintenance, and modulation of inflammatory processes, and also aging, apoptosis, platelet aggregation, oxidative stress and synaptic activity (3). Neuroprotective potential of COX-2 inhibitors and 5-LOX inhibitors has been documented in different experimental model of neurotoxicity (4,5).…”

Development, characterization and nasal delivery of rosmarinic acid-loaded solid lipid nanoparticles for the effective management of Huntington’s disease

“…Briefly, the rats were exposed to prior training session on the rotarod (constant speed of 25 rpm; rod diameter 7 cm) for 1st, 5th, 10th, 15th day after 3-NP administration. The average fall of time was recorded and expressed as percentage fall off time (Kalonia et al, 2009). …”

“…Before subjecting the animals to a cognitive task, all animals were individually placed in the activity meter and the total activity count was measured for 10 min. The locomotor activity was expressed in terms of total photobeam counts per 10 min per animal (Kalonia et al, 2009). …”

“…A ceiling of 120 s is employed at the end after which the rat is removed and placed in the cage by hand and receives, if it is the case, a score of 120 s. The test procedure is identical for all rats tested and performed in the same environment, preferably in the morning. Time taken to traverse rat from start platform to their home cage was measured along with their number of slipping errors (Kalonia et al, 2009). …”