Protective effect of irbesartan, an angiotensin II receptor antagonist, alone and in combination with aspirin on middle cerebral artery occlusion model of focal cerebral ischemia in rats.
The present study was designed to test pretreatment multiple doses of irbesartan (IRB) 50 mg, aspirin (ASP) 100 mg and the combination of both drugs for 7 days on middle cerebral artery-occluded (MCAO) rats. Focal cerebral ischemia was induced by MCA occlusion for 2 hours followed by reperfusion for 22 hours. After 24 hours of ischemia, grip strength and locomotor activity tests were performed. Animals were immediately sacrificed, infarct volume was measured followed by the estimation of markers of oxidative stress in the whole brains. Locomotor activity and grip strength were improved in IRB- and ASP-treated rats. Infarct volume was reduced in both IRB and ASP pretreatment as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase were observed following MCAO. Pretreatment of IRB and ASP showed the reduction in TBARS, elevation in GSH, SOD and catalase levels as compared with MCAO rats. The protective effects of IRB, an angiotensin II receptor antagonist having affinity for AT(1) receptor subtypes, could be due to inhibition of AT( 1) receptor expression in addition to its neuroprotective and free radical scavenging properties in cerebral ischemia. Further, it may be possible that the combination of IRB and ASP may be useful as an add-on therapy and would yield beneficial effects, if administered immediately following the ischemia in reducing the severity of the neurological deficits. However, our results are preliminary, further studies with posttreatment of IRB and ASP are required to provide more firm view.
Pratap
Ravi
R
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
Pillai
K K
KK
Khanam
Razia
R
Islam
Fakhrul
F
Ahmad
Shibli Jameel
SJ
Akhtar
Mohammad
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000077405:Irbesartan; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010784:Photomicrography; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D013777:Tetrazoles; D017392:Thiobarbituric Acid Reactive Substances; D000077405:Irbesartan; D001241:Aspirin