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Author(s)

     Mihaela Flueraru, Remmick So, William Willmore, Michael Poulter, Tony Durst, Martin Charron, James Wright

Title

      Cytotoxicity and Cytoprotective Activity of Naphthalenediols in Rat Cortical Neurons.

Publication Name

     Chemical Research in Toxicology

Publication Type

     Journal
Publisher
     
Place
     
Editor(s)
     
Number
     
School
     
Volume
      19
Chapter
     
Pages
      1221-1227
Other Publication Information
     
Publication Year
     2006
Abstract
     Some members of the naphthalenediol family have been shown in previous work on PC-12 cells to act as effective antioxidants while being relatively nontoxic. In the present work, we extend that study to examine the effect of naphthalenediols on rat primary cortical neurons exposed to AAPH (2,2'-azobis (2-amidinopropane) hydrochloride), a source of peroxyl radicals. Compds. tested included the acetylated forms of 1,2-naphthalenediol, i.e., 1,2-ND, as well as 1,4-ND, 2,3-ND, 1,8-ND, and the known highly potent antioxidant (-)-epigallocatechin gallate (EGCG). In cytotoxicity studies, cells were exposed to the compds. for 24 h, leading to obsd. toxicity in the order of 1,4-ND > 1,2 ND .mchgt. 2,3-ND EGCG > 1,8-ND. In cytoprotection studies, the desired compds. were incubated with neurons prior to AAPH exposure, and live cell counts were detd. by trypan blue and/or MTT assays. Excellent protection, superior to EGCG, was provided by 2,3-ND and 1,8-ND. Addnl. studies using glutamate as a stressor showed that 1,8-ND had a significant protective effect at concns. as low as 500 nM. The results can be understood on the basis of the tendency (or lack thereof) to form the corresponding quinone, which in turn depends on whether or not there is a loss of aromaticity in the ring adjacent to the quinone moiety. Thus, certain members of the family of naphthalenediols are quite cytotoxic, whereas others show promise as neuroprotective antioxidants.
Keywords
     naphthalenediols, cytotoxicity, antioxidants, oxidative stress
Website
     http://
Paper Status
     Published
DOI / Publication ID
     



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