Cellular defence mechanisms in the striatum of young and aged rats subchronically exposed to manganese.
A deficiency of striatal dopamine (DA) is generally accepted as an expression of manganese (Mn) toxicity in experimental animals. Since compromised cellular defence mechanisms may be involved in Mn neurotoxicity, we investigated the response of the neuronal antioxidant system [ascorbic acid (AA) oxidation, glutathione (GSH) and uric acid levels] and neurochemical changes in the striatum in aged rats exposed to Mn. Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), AA, dehydroascorbic acid (DHAA), GSH and uric acid were determined after subchronic oral exposure to MnCl2 200 mg/kg (3-month-old rats) and 30-100-200 mg/kg (20-month-old-rats). Aged rats had basal levels of striatal DA, DOPAC, HVA, 5-HT, 5-HIAA, GSH and AA lower than those of young rats. In the striatum of aged rats, Mn induced biphasic changes in the levels of DA, DOPAC, HVA (an increase at the lower dose and a decrease at the higher dose) and DHAA (opposite changes). Mn decreased GSH levels and increased uric acid levels both in the striatum and in synaptosomes in all groups of aged rats. All of these parameters were affected to a lesser extent in young rats. In conclusion, the response of cellular defence mechanisms in aged rats is consistent with a Mn-induced increase in the formation of reactive oxygen species. An age-related impairment of the neuronal antioxidant system may play an enabling role in Mn neurotoxicity.
Desole
M S
MS
Institute of Pharmacology, University of Sassari, Italy.
Esposito
G
G
Migheli
R
R
Fresu
L
L
Sircana
S
S
Zangani
D
D
Miele
M
M
Miele
E
E
D000375:Aging / Q000502:physiology*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D020149:Manganese Poisoning; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D017382:Reactive Oxygen Species; D014527:Uric Acid; D012701:Serotonin; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine