Arsenite induces oxidative injury in rat brain: Synergistic effect of iron: Annals of the New York academy of sciences

Su Feng Fan, Pei Ling Chao, Anya Maan Yuh Lin

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

9 Scopus citations


Sodium arsenite (arsenite)-induced neurotoxicity and its interaction with ferrous citrate (iron) was investigated in rat brain. In vitro data showed that arsenite (1-10 μmolL) concentration dependently increased lipid peroxidation and the potency of arsenite was less than that of iron. The oxidative activity of arsenite, sodium arsenate (arsenate), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were evaluated by inducing lipid peroxidation in cortical homogenates, and the potency for this effect was as follows: arsenite > arsenate > MMA and DMA. Several well-known antioxidants, including glutathione, melatonin, and β-estradiol inhibited arsenite-induced lipid peroxidation in a concentration-dependent manner. Our in vivo study employed intranigral infusion of arsenite (5 nmol) in the substantia nigra (SN) of anesthetized rats. Four hours to 7 days after infusion, lipid peroxidation was elevated while glutathione was depleted in the infused SN. The dopamine content in the striatum ipsilateral to arsenite-infused SN was first elevated 24 h and then decreased 7 days after intranigral infusion of arsenite. Using pretreatment of l-buthionine-[S,R]-sulfoximine (l-BSO, i.c.v.) to reduce glutathione content in rat brain, arsenite-induced oxidative injury was augmented. Low doses of arsenite (1.5 nmol) and iron (3 nmol) alone induced minimal oxidative injury; however, co-infusion of arsenite and iron augmented neurotoxicity, including elevated lipid peroxidation and reduced striatal dopamine content. Moreover, expression of heme oxygenase-1, α-synuclein aggregation, and DNA fragmentation were significantly enhanced in SN co-infused with low doses of arsenite and iron. Taken together, our study demonstrates that arsenite was less potent than iron in inducing oxidative stress. Furthermore, concomitant arsenite and iron potentiated oxidative injury in the nigrostriatal dopaminergic system, indicating that interaction of metals plays a more clinically-relevant role in pathophysiology of central nervous system neurodegeneration.

Original languageEnglish
Title of host publicationNeuroprotective Agents
Subtitle of host publicationNinth International Conference
PublisherBlackwell Publishing Inc.
Number of pages9
ISBN (Print)9781573317771
StatePublished - Jun 2010

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Arsenite
  • Iron
  • Neurotoxicity


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