Kalonia Harikesh, Kumar Puneet, Kumar Anil, Nehru Bimla
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advance Study, Panjab University, Chandigarh, India.
Inflammopharmacology. 2009 Aug;17(4):211-9. doi: 10.1007/s10787-009-0012-1. Epub 2009 Jul 26.
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.
长期以来，氧化应激一直被认为与谷氨酸通过N-甲基-D-天冬氨酸（NMDA）受体发挥的神经毒性作用有关。因此，本研究旨在探讨罗非昔布和咖啡酸对氧化应激、线粒体功能障碍以及与NMDA受体介导的兴奋性毒性相关神经元的影响。咖啡酸是一种著名的抗氧化类黄酮，具有抗炎和免疫调节等作用。本研究旨在探讨咖啡酸和罗非昔布及其组合对喹啉酸（QA）诱导的氧化损伤、线粒体功能障碍和组织学改变的抗氧化样作用。纹状体内注射喹啉酸（300 nmol）显著增加了离体纹状体中的氧化应激（脂质过氧化增加、亚硝酸盐浓度升高、超氧化物歧化酶和过氧化氢酶减少），改变了线粒体复合酶活性并导致组织学改变。咖啡酸（5和10 mg/kg，口服）和罗非昔布（10和20 mg/kg，口服）治疗21天显著减轻了离体纹状体中的氧化损伤和复合酶线粒体活性的损害。此外，罗非昔布（10 mg/kg，口服）和咖啡酸（5 mg/kg，口服）的亚有效剂量组合增强了它们的保护作用，与它们各自的作用相比具有显著性。本研究表明咖啡酸和罗非昔布组合对QA诱导的大鼠离体氧化损伤、线粒体和组织学改变具有治疗作用。
