Rubratoxin B elicits antioxidative and DNA repair responses in mouse brain.
Rubratoxin B (RB) is a mycotoxin with potential neurotoxic effects that have not yet been characterized. Based on existing evidence that RB interferes with mitochondrial electron transport to produce oxidative stress in peripheral tissues, we hypothesized that RB would produce oxidative damage to macromolecules in specific brain regions. Parameters of oxidative DNA damage and repair, lipid peroxidation, and superoxide dismutase (SOD) activity were measured across six mouse brain regions 24 h after administration of a single dose of RB. Lipid peroxidation and oxidative DNA damage were either unchanged or decreased in all brain regions in RB-treated mice compared with vehicle-treated mice. Concomitant with these decreased indices of oxidative macromolecular damage, SOD activity was significantly increased in all brain regions. Oxyguanosine glycosylase activity (OGG1), a key enzyme in the repair of oxidized DNA, was significantly increased in three brain regions--cerebellum (CB), caudate/putamen (CP), and cortex (CX)--but not in the hippocampus (HP), midbrain (MB), and pons/medulla (PM). The RB-enhanced OGG1 catalytic activity in these brain regions was not due to increased OGG1 protein expression, but was a result of enhanced catalytic activity of the enzyme. In conclusion, specific brain regions responded to an acute dose of RB by significantly altering SOD and OGG1 activities to maintain the degree of oxidative DNA damage equal to, or less than, that of normal steady-state levels.
Sava
V
V
University of South Florida, Tampa, FL 33612, USA.
Mosquera
D
D
Song
S
S
Stedeford
T
T
Calero
K
K
Cardozo-Pelaez
F
F
Harbison
R
R
Sanchez-Ramos
J
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002421:Caudate Nucleus / Q000737:chemistry; D002531:Cerebellum / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects; D045647:DNA Glycosylases / Q000032:analysis / Q000378:metabolism; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008636:Mesencephalon / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009183:Mycotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011149:Pons / Q000737:chemistry; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D009183:Mycotoxins; D017392:Thiobarbituric Acid Reactive Substances; C100297:rubratoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D003849:Deoxyguanosine