Pretreatment with potassium channel blockers of 4-aminopyridine and tetraethylammonium attenuates behavioural symptoms of Parkinsonism induced by intrastriatal injection of 6-hydroxydopamine; the role of lipid peroxidation.
OBJECTIVE
Potassium channels participate in cellular and molecular signalling pathways regulating the life and death of neurons. In this study, effect of pretreatment with potassium channel blockers of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the behavioural symptoms of 6-hydroxydopamine (6-OHDA)-induced Parkinsonism was evaluated.


METHODS
6-OHDA was injected into right striatum of adult male Wistar rats using stereotaxic surgery. Severity of 6-OHDA-induced Parkinsonism was assessed by conventional behavioural tests. 4-AP and TEA were injected twice per day intraperitoneally, before 6-OHDA injection to 15 days after that. Also, malondialdehyde (MDA) concentration as a marker of oxidative stress was measured in rat sera.


RESULTS
Pretreatment with 4-AP (0.5 and 1 mg/kg) and TEA (2 and 5 mg/kg) attenuated significantly behavioural symptoms of 6-OHDA-induced Parkinsonism. Application of both 4-AP and TEA together was more effective than the effect of each one of these blockers alone. 6-OHDA increased MDA concentration but pretreatment with 4-AP prevented of 6-OHDA-induced increase in MDA. On the other hand, pretreatment with TEA and combination of TEA and 4-AP could not prevent of 6-OHDA-induced oxidative stress.


CONCLUSIONS
Since severity of behavioural symptoms of 6-OHDA-induced Parkinsonism is correlated to the degree of nigral dopaminergic cell death, we suggest that antiparkinsonism effect of TEA and 4-AP was mediated by their neuroprotective effect. Because, both Parkinsonism in rat and PD in human, the main pathophysiological hallmark, is neurodegeneration of dopaminergic neurons in substantia nigra, we suggest doing clinical trials for evaluation of effectiveness of 4-AP and TEA in slowing down of PD progress.
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Hashem
H
Haghdoost-Yazdi
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Hossein
H
Piri
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Ayda
A
Faraji
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Negin
N
Fraidouni
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Tahereh
T
Dargahi
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Marzieh
M
Mahmudi
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Mahmud
M
Alipour Heidari
D015761:4-Aminopyridine / Q000627:therapeutic use*; D018663:Adrenergic Agents; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007839:Functional Laterality / Q000187:drug effects; D008297:Male; D001523:Mental Disorders / Q000209:etiology* / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D004856:Postural Balance / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000097:blood
C575035:(Z)2-(5-(4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid; D018663:Adrenergic Agents; D026902:Potassium Channel Blockers; D045162:Thiazolidinediones; D019789:Tetraethylammonium; D016627:Oxidopamine; D015761:4-Aminopyridine; D001058:Apomorphine
4-AP; 6-OHDA; Behavioural symptoms; Malondialdehyde; TEA