Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India.
Behav Brain Res. 2011 Jan 1;216(1):220-8. doi: 10.1016/j.bbr.2010.07.040. Epub 2010 Aug 7.
A possible neuroprotective role has been recently suggested for 3H3MGCoA reductase inhibitors (statins). Here, we sought to determine neuroprotective effect of statins in quinolinic acid induced neurotoxicity in rats. Rats were surgically administered quinolinic acid and treated with Atorvastatin (10, 20 mg/kg), simvastatin (15, 30 mg/kg) and fluvastatin (5, 10 mg/kg) once daily up to 3 weeks. Atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10 mg/kg) treatment significantly attenuated the quinolinic acid induced behavioral (locomotor activity, rotarod performance and beam walk test), biochemical (lipid peroxidation, nitrite concentration, SOD and catalase), mitochondrial enzyme complex alterations in rats suggesting their free radical scavenging potential. Additionally, atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10 mg/kg) significantly decrease the TNF-α level and striatal lesion volume in quinolinic acid treated animals indicating their anti-inflammatory effects. In comparing the protective effect of different statins, atorvastatin is effective at both the doses while simvastatin and fluvastatins at respective lower doses were not able to produce the protective effect in quinolinic acid treated animals. These modulations can account, at least partly, for the beneficial effect of statins in our rodent model of striatal degeneration. Our findings show that statins could be explored as possible neuroprotective agents for neurodegenerative disorders such as HD.
他汀类药物(3H3MGCoA 还原酶抑制剂)可能具有神经保护作用。本研究旨在确定他汀类药物对喹啉酸诱导的大鼠神经毒性的神经保护作用。大鼠接受手术给予喹啉酸,并每日一次给予阿托伐他汀(10、20mg/kg)、辛伐他汀(15、30mg/kg)和氟伐他汀(5、10mg/kg)治疗,共 3 周。阿托伐他汀(10、20mg/kg)、辛伐他汀(30mg/kg)和氟伐他汀(10mg/kg)治疗显著减轻了喹啉酸诱导的行为(运动活性、转棒性能和平衡木行走测试)、生化(脂质过氧化、亚硝酸盐浓度、SOD 和过氧化氢酶)和大鼠线粒体酶复合物改变,表明其具有自由基清除潜力。此外,阿托伐他汀(10、20mg/kg)、辛伐他汀(30mg/kg)和氟伐他汀(10mg/kg)显著降低了喹啉酸处理动物的 TNF-α水平和纹状体损伤体积,表明其具有抗炎作用。在比较不同他汀类药物的保护作用时,阿托伐他汀在两种剂量下均有效,而辛伐他汀和氟伐他汀在各自的较低剂量下未能在喹啉酸处理的动物中产生保护作用。这些调节至少可以部分解释他汀类药物在我们的纹状体退化啮齿动物模型中的有益作用。我们的研究结果表明,他汀类药物可能被探索为神经退行性疾病(如 HD)的潜在神经保护剂。