Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum.
It is well established that aluminum (Al) is a neurotoxic agent that induces the production of free radicals in brain. Accumulation of free radicals may cause degenerative events of aging such as Alzheimer's disease. On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, AbetaPP female transgenic (Tg2576) (Tg) and wild-type mice (5 months of age) were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg) dissolved in tap water until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was removed and processed to examine the following oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of Cu-ZnSOD, GR, and CAT was evaluated by real-time RT-PCR. Aluminum concentration in hippocampus was also determined. The biochemical changes observed in this tissue suggest that Al acts as a pro-oxidant agent. Melatonin exerts an antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD, CAT, and GR evaluated in presence of Al and Mel, with independence of the animal model.
Garcia
Tania
T
Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Rovira i Virgili University, Sant Llorenç 21, Reus, Catalonia, Spain.
Esparza
José L
JL
Nogués
M Rosa
MR
Romeu
Marta
M
Domingo
José L
JL
Gómez
Mercedes
M
D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D007773:Lactates / Q000633:toxicity*; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress; D058255:Protease Nexins; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
D017607:Aluminum Compounds; D016564:Amyloid beta-Protein Precursor; D007773:Lactates; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D008550:Melatonin; C104223:aluminum lactate