Neuroprotective potentials of candesartan, atorvastatin and their combination against stroke induced motor dysfunction.
Cerebral ischaemia is a leading cause of death and disability. The objective of the present investigation was to explore the neuroprotective potentials of candesartan and atorvastatin alone and their combination against the cerebral ischaemia induced behavioral, biochemical, and mitochondrial dysfunction. Male Wistar rats (200-220 g) were subjected to bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion. Candesartan (0.1 and 0.3 mg/kg) and atorvastatin (10 and 20 mg/kg) were pretreated for 7 days before animals were subjected to ischaemia reperfusion injury. Various behavioral tests (locomotor activity and rotarod performance), biochemical parameters (Malondialdehyde levels, nitrite concentration, superoxide dismutase and catalase activity, redox ratio, and GST) and mitochondrial enzyme (Complex I, II, III, and IV) dysfunctions were measured in cerebral cortex, striatum and hippocampus of the ischaemic brain. Seven days candesartan (0.1 and 0.3 mg/kg) or atorvastatin (10 and 20 mg/kg) pretreatment significantly attenuated neurobehavioral alterations, oxidative damage and restored mitochondrial enzyme dysfunction as compared to control (I/R) group. Further, combined treatment of candesartan (0.1 mg/kg) and atorvastatin (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone. Present study suggests the protective effect of candesartan and atorvastatin and their combination against ischaemia reperfusion induced behavioral and biochemical alterations in rats.
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India.
Vaibhav
V
Gaur
Anil
A
Kumar
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000069059:Atorvastatin; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D020521:Stroke / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013777:Tetrazoles; D000069059:Atorvastatin; C081643:candesartan