Pro-oxidant activity of aluminum in the rat hippocampus: gene expression of antioxidant enzymes after melatonin administration.
Aluminum (Al)-induced pro-oxidant activity and the protective role of exogenous melatonin, as well as the mRNA levels of some antioxidant enzymes, were determined in the hippocampi of rats following administration of Al and/or melatonin. Two groups of male rats were intraperitoneally injected with Al (as Al lactate) or melatonin only, at doses of 7 and 10 mg/kg/day, respectively, for 11 weeks. During this period, a third group of animals received Al (7 mg/kg/day) plus melatonin (10 mg/kg/day). At the end of the treatment, hippocampus was removed and processed to examine the following oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Gene expression of Cu-ZnSOD, MnSOD, GPx, and CAT was evaluated by real-time RT-PCR. On the other hand, Al, Fe, Mn, Cu, and Zn concentrations in hippocampus were also determined. The results show that Al exposure promotes oxidative stress in the rat hippocampus, with an increase in Al concentrations. The biochemical changes observed in this tissue indicate that Al acts as pro-oxidant agent, while melatonin exerts antioxidant action by increasing the mRNA levels of the antioxidant enzymes evaluated. The protective effects of melatonin, together with its low toxicity and its capacity to increase mRNA levels of antioxidant enzymes, suggest that this hormone might be administered as a potential supplement in the treatment of neurological disorders in which oxidative stress is involved.
Gómez
Mercedes
M
Laboratory of Toxicology and Environmental Health, Rovira i Virgili University, San Lorenzo 21, 43201 Reus, Spain.
Esparza
José L
JL
Nogués
M Rosa
MR
Giralt
Montserrat
M
Cabré
Maria
M
Domingo
José L
JL
D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007274:Injections, Intraperitoneal; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017607:Aluminum Compounds; D007773:Lactates; D016877:Oxidants; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D008550:Melatonin; C104223:aluminum lactate