title: Cytotoxicity and cytoprotective activity of naphthalenediols in rat cortical neurons.
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. Compounds tested included the acetylated forms of 1,2-naphthalenediol, that is, 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 cytoxicity studies, cells were exposed to the compounds for 24 h, leading to observed toxicity in the order of 1,4-ND > 1,2 ND >> 2,3-ND approximately EGCG > 1,8-ND. In cytoprotection studies, the desired compounds were incubated with neurons prior to AAPH exposure, and live cell counts were determined by trypan blue and/or MTT assays. Excellent protection, superior to EGCG, was provided by 2,3-ND and 1,8-ND. Additional studies using glutamate as a stressor showed that 1,8-ND had a significant protective effect at concentrations 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.
authors.affiliation: Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Canada K1S 5B6, Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Canada.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Flueraru
authors.forename: Remmick
authors.initials: R
authors.lastname: So
authors.forename: William G
authors.initials: WG
authors.lastname: Willmore
authors.forename: Michael O
authors.initials: MO
authors.lastname: Poulter
authors.forename: Tony
authors.initials: T
authors.lastname: Durst
authors.forename: Martin
authors.initials: M
authors.lastname: Charron
authors.forename: James S
authors.initials: JS
authors.lastname: Wright
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D005260:Female; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley