Protection in glutamate-induced neurotoxicity by imidazoline receptor agonist moxonidine.
In the present study we investigated the effects of mixed imidazoline-1 and alpha(2)-adrenoceptor agonist, moxonidine, in glutamate-induced neurotoxicity in frontal cortical cell cultures of rat pups by dye exclusion test. Also, phosphorylated p38 mitogen activated protein kinases (p-p38 MAPK) levels were determined from rat frontal cortical tissue homogenates by two dimensional gel electrophoresis and semidry western blotting. Glutamate at a concentration of 10(-6) M was found neurotoxic when applied for 16 hr in cell cultures. Dead cell mean scores were 12.8 +/- 0.5 for control and 52.3 +/- 4.8 for glutamate (p < .001). On the other hand, p-p38 MAPK levels start to increase at a glutamate concentration of 10(-7) M for 20 min application. Moxonidine was found to have an U-shape neuroprotective effect in glutamate-induced neurotoxicity in neuronal cell culture experiments. Even though moxonidine did not induce neurotoxicity alone between the doses of 10(-8) to 10(-4) M concentrations in cell culture series, it caused the reduction of glutamate-induced dead cell population 23.07 +/- 3.6% in 10(-6) M and 26.7 +/- 2.1% in 10(-5) M concentrations (p <.001 for both, in respect to control values). The protective effect of moxonidine was confirmed in 10(-8) and 10(-7) M, but not in higher concentrations in glutamate neurotoxicity in gel electrophoresis and western blotting of p-p38 MAPK levels. In addition to other studies that revealed an antihypertensive feature of moxonidine, we demonstrated a possible partial neuroprotective role in lower doses for it in glutamate-mediated neurotoxicity model.
Bakuridze
Kakhi
K
Department of Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia.
Savli
Evren
E
Gongadze
Niko
N
Baş
Duygu Belkis
DB
Gepdiremen
Akçahan
A
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005625:Frontal Lobe / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D054755:Imidazoline Receptors / Q000819:agonists*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007093:Imidazoles; D054755:Imidazoline Receptors; D018696:Neuroprotective Agents; D018698:Glutamic Acid; C043482:moxonidine; D048051:p38 Mitogen-Activated Protein Kinases