Dopaminergic system activity and cellular defense mechanisms in the striatum and striatal synaptosomes of the rat subchronically exposed to manganese.
In 6-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), uric acid and glutathione (GSH) were determined by HPLC in the striatum and striatal synaptosomes after subchronic oral exposure to MnCl2 50-100-150 mg/kg. Mn significantly decreased levels of DA and GSH and increased levels of DHAA and uric acid both in the striatum and synaptosomes. In synaptosomes, individual total Mn doses/rat were directly correlated with individual DOPAC/DA ratio values (r = +0.647), uric acid (r = +0.532) and DHAA levels (r = +0.889) and inversely correlated with DA (r = -0.757) and GSH levels (r = -0.608). In turn, GSH levels were inversely correlated with uric acid (r = -0.451) and DHAA levels (r = -0.460). In conclusion, the response of striatal cellular defense mechanisms (increase in AA oxidation, decrease in GSH levels) correlated well with changes in markers of dopaminergic system activity and increase in uric acid levels. The latter provides evidence of an Mn-induced oxidative stress mediated by xanthine oxidase.
Desole
M S
MS
Institute of Pharmacology, University of Sassari, Italy.
Miele
M
M
Esposito
G
G
Migheli
R
R
Fresu
L
L
De Natale
G
G
Miele
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003683:Dehydroascorbic Acid / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism
D000975:Antioxidants; D015102:3,4-Dihydroxyphenylacetic Acid; D014527:Uric Acid; D008345:Manganese; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine; D003683:Dehydroascorbic Acid