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Effect of manganese exposure and antioxidant therapy on oxidative stress in the rat brain
Author(s) -
Fordahl Steven,
Cooney Paula,
Milatovic Dejan,
Aschner Michael,
Erikson Keith
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.921.7
Subject(s) - oxidative stress , glutathione , antioxidant , chemistry , glutathione peroxidase , endocrinology , medicine , weanling , catalase , glutathione reductase , biochemistry , enzyme
Manganese (Mn) is an essential element implicated in the etiologies of metal induced neurological disorders. Over‐exposure to Mn results in its accumulation in iron‐rich brain regions leading to symptoms analogous to Parkinson's disease. Mechanisms governing this response are largely undefined though it is hypothesized that Mn‐induced oxidative stress may play a role. In this study we examined weanling rats exposed to Mn (1 g/L d.i. water) for total glutathione (GSH), glutathione peroxidase (GPx) and catalase mRNA, and F2‐isoprostane (F2‐IsoP) production in the caudate putamen (CP) and hippocampus (HC). N‐acetyl‐cysteine (NAC; 200 mg/kg) or (−)‐epigallocatechin‐3‐gallate (EGCG; 5mg/kg) injections were administered to observe any protective effect against Mn‐induced oxidative stress. Mn accumulated significantly versus control in each region (p < 0.05) in Mn‐exposed groups. This did not correspond to alterations in total GSH or production of F2‐IsoPs. EGCG was also associated with significant Mn accumulation in the CP (p < 0.05). Significant up‐regulation of GPx gene expression (p < 0.05) observed in the HC correlated with increased Mn levels, and was augmented by EGCG. These data suggest a biological response in antioxidant gene expression to Mn exposure, even in the absence of identifiable oxidative stress. Additionally, antioxidant therapy may enhance this response.