Comparative neuroprotective profile of statins in quinolinic acid induced neurotoxicity in rats.
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.
Kalonia
Harikesh
H
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India.
Kumar
Puneet
P
Kumar
Anil
A
D000704:Analysis of Variance; D000818:Animals; D000069059:Atorvastatin; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D018696:Neuroprotective Agents; D009573:Nitrites; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000077340:Fluvastatin; D000069059:Atorvastatin; D019821:Simvastatin; D013482:Superoxide Dismutase; D017378:Quinolinic Acid