Zinc reverses malathion-induced impairment in antioxidant defenses.
Malathion toxicity has been related to the inhibition of acetylcholinesterase and induction of oxidative stress, while zinc has been shown to possess neuroprotective effects in experimental and clinical studies. In the present study the effect of zinc chloride (zinc) was addressed in adult male Wistar rats following a long-term treatment (30 days, 300mg/L in tap water ad libitum) against an acute insult caused by a single malathion exposure (250mg/kg, i.p.). Malathion produced a significant decrease in hippocampal acetylcholinesterase, as well as a decrease in the activity of several hippocampal antioxidant enzymes: glutathione reductase, glutathione S-transferase, catalase and superoxide dismutase. The pretreatment with zinc did not completely prevent acetylcholinesterase activity impairment; however, antioxidant activity was completely restored. Zinc administration significantly increased HSP60, but not HSP70, expression. The HSP60 increase suggests a novel zinc-dependent pathway, which may be related to a counteracting mechanism against malathion effects. Based on these results the following hypothesis can be presented: the published "pro-oxidative" effect of malathion may be related, among others, to compromised antioxidant defenses, while the zinc "antioxidant" action may be related to the preservation of antioxidant defenses. In conclusion, our data points to the inhibition of antioxidant enzymes as an important non-cholinergic effect of malathion, which can be rescued by oral zinc treatment.
Franco
Jeferson L
JL
Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
Posser
Thais
T
Mattos
Jacó J
JJ
Trevisan
Rafael
R
Brocardo
Patricia S
PS
Rodrigues
Ana Lúcia S
AL
Leal
Rodrigo B
RB
Farina
Marcelo
M
Marques
Maria R F
MR
Bainy
Afonso C D
AC
Dafre
Alcir L
AL
D000110:Acetylcholinesterase / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D018834:Chaperonin 60 / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004347:Drug Interactions; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008294:Malathion / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology*
D018834:Chaperonin 60; D002712:Chlorides; D002800:Cholinesterase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D017967:Zinc Compounds; C016837:zinc chloride; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000110:Acetylcholinesterase; D008294:Malathion