Dieldrin elicits a widespread DNA repair and antioxidative response in mouse brain.
Dieldrin is an organochlorine pesticide that is toxic for monoaminergic neurons. This study was designed to test the hypothesis that a weak DNA repair response to dieldrin by nigrostriatal dopaminergic (DA) neurons results in depletion of striatal DA. The activity of the mammalian base excision repair enzyme oxyguanosine glycosylase was utilized as the index of DNA repair. Other measures of oxidative stress were also studied, including the regional distribution of lipid peroxidation and superoxide dismutase (SOD) activity. The effects of acute and slow infusion of dieldrin on striatal DA levels were biphasic with a transient initial depression followed by increases beyond normal steady-:state levels. Dieldrin administration caused a global oxidative stress evidenced by increased levels of lipid peroxidation in all brain regions, an effect consistent with its capacity to affect mitochondrial bioenergetics. Dieldrin also elicited strong antioxidative and DNA repair responses across the entire mouse brain. Although mitochondrial SOD was not as increased in midbrain as it was in other regions following a cumulative dose of 24 mg/kg, this response, along with the robust DNA repair response, appeared to be sufficient to protect potentially vulnerable DA neurons from cytotoxicity. However, the long-:term consequences of chronic low-:dose dieldrin exposure remain to be studied, especially in light of the concept of "slow excitotoxicity,'' which postulates that even a mild bioenergetic compromise can over time result in the demise of neurons.
Sava
Vasyl
V
Department of Neurology, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA.
Velasquez
Adriana
A
Song
Shijie
S
Sanchez-Ramos
Juan
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004026:Dieldrin / Q000737:chemistry / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D004247:DNA; D013482:Superoxide Dismutase; D004026:Dieldrin; D004298:Dopamine