Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats.
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.
Kalonia
Harikesh
H
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advance Study, Panjab University, Chandigarh, India.
Kumar
Puneet
P
Kumar
Anil
A
Nehru
Bimla
B
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D002109:Caffeic Acids; D007783:Lactones; D009573:Nitrites; D016194:Receptors, N-Methyl-D-Aspartate; D013450:Sulfones; C116926:rofecoxib; D013482:Superoxide Dismutase; D017378:Quinolinic Acid; C040048:caffeic acid