Effect of MAO-B inhibition against ischemia-induced oxidative stress in the rat brain. Comparison with a rational antioxidant.
An increasing number of reports suggest the involvement of oxidative stress in neurodegenerative diseases where the increased formation of reactive oxygen species (ROS) leads to neuronal damage and cell death. Dopamine may contribute to neurodegenerative disorders such as Parkinson's disease and ischemia/reperfusion-induced damage. Monoamine oxidase (MAO) enzyme (particularly MAO-B) is responsible for metabolizing dopamine and plays an important role in oxidative stress through altering the redox state of neuronal and glial cells. MAO participates in the generation of hydroxyl radicals during ischemia/reperfusion. This suggests the possible use of MAO inhibitors as neuroprotective agents for treating ischemic injury. The protective effect of deprenyl (N-methyl-N-(1-methyl-2-phenyl-ethyl)-prop-2-yn-1-amine, CAS 14611-51-9) (2 and 10 mg/kg), a MAO-B inhibitor, and beta-carotene (10 and 20 mg/kg), a natural antioxidant, was examined in a rat model of cerebral ischemia. Ischemia was induced in rats by bilateral carotid artery occlusion for 1 h followed by declamping for another hour. The effect of the drugs on the brain activity of lactate dehydrogenase (LDH) and some of the oxidative stress biomarkers such as brain activity of superoxide dismutase (SOD) and catalase (CAT) enzymes and brain malondialdehyde (MDA) content was determined. In addition, the content of catecholamines such as noradrenaline (NA) and dopamine (DA) was determined. Deprenyl decreased the ischemia-induced elevation of LDH activity and MDA content and normalized the SOD activity. In addition, deprenyl increased the CAT activity back to normal, and increased the noradrenaline and dopamine content in the brain of rats. Beta-carotene administration ameliorated the effect of ischemia followed by reperfusion (I/R) demonstrated as decreasing the LDH activity and MDA content and by increasing the SOD activity. The drug also increased CAT activity in the brain of rats. However, beta-carotene did not alter the NA and DA content. These results indicate that deprenyl protected the rat brains against the ischemia-induced oxidative damage, an effect which might be explained through multiple mechanisms, possibly due to reduction of dopamine catabolism with a subsequent increased activity on dopaminergic D2 receptors and suppressing the action of ROS as well.
Seif-El-Nasr
Mona
M
Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. seifelnasr.mona@gmail.com
Atia
Amina S
AS
Abdelsalam
Rania M
RM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009474:Neurons / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D012642:Selegiline / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D019207:beta Carotene / Q000494:pharmacology
D000975:Antioxidants; D008996:Monoamine Oxidase Inhibitors; D019207:beta Carotene; D012642:Selegiline; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase; D009638:Norepinephrine