title: Inhibition by polyphenolic phytochemicals and sulfurous compounds of the formation of 8-chloroguanosine mediated by hypochlorous acid, human myeloperoxidase, and activated human neutrophils.
abstract: Hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) of activated neutrophils can react with nucleic acid bases to form chlorinated nucleosides such as 8-chloroguanosine (Cl-Guo). Chlorination is enhanced by nicotine. We investigated the effects of various natural antioxidants including polyphenolic phytochemicals on the formation of Cl-Guo by HOCl in the presence and the absence of nicotine. Polyphenols, including catechins, curcumin, resveratrol, silibinin, and sulfurous compound α-lipoic acid, were found to inhibit both HOCl- and human MPO-induced Cl-Guo formation dose-dependently. Among the test compounds, (-)-epigallocatechin gallate (EGCG) showed the strongest inhibitory effect. Cl-Guo formation, mediated by activated human neutrophils in the presence of nicotine, was inhibited by EGCG, silibinin, and α-lipoic acid. These results suggest that polyphenols and sulfurous compounds have the potential to inhibit the induction of nucleobase damage mediated by chlorination, with possible application to reducing DNA damage associated with inflammation and cigarette-smoke inhalation.
authors.affiliation: Marine Biochemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. nakanot@bios.tohoku.ac.jp
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nakano
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Masuda
authors.forename: Toshinori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D059808:Polyphenols / Q000494:pharmacology*; D012965:Sodium Chloride / Q000378:metabolism; D013457:Sulfur Compounds / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D059808:Polyphenols; D013457:Sulfur Compounds; D006151:Guanosine; C043808:8-chloroguanosine; D012965:Sodium Chloride; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase