TY - JOUR
T1 - Inhibition by polyphenolic phytochemicals and sulfurous compounds of the formation of 8-chloroguanosine mediated by hypochlorous acid, human myeloperoxidase, and activated human neutrophils
AU - Nakano, Toshiki
AU - Masuda, Mitsuharu
AU - Suzuki, Toshinori
AU - Ohshima, Hiroshi
N1 - Funding Information:
Most of this study was done at the International Agency for Research on Cancer, World Health Organization (IARC/WHO), Lyon, France, when the authors were at the Laboratory of Endogenous Cancer Risk Factors (ECR). The authors thank Mrs. P. Collard at IARC for secretarial assistance and the staff at ECR, IARC, for valuable discussion and support. Financial support was provided by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (to T.N.).
PY - 2012
Y1 - 2012
N2 - 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 cigarettesmoke inhalation.
AB - 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 cigarettesmoke inhalation.
KW - Chlorination
KW - Hypochlorous acid
KW - Neutrophils
KW - Nicotine
KW - Polyphenolic phytochemicals
UR - http://www.scopus.com/inward/record.url?scp=84871624539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871624539&partnerID=8YFLogxK
U2 - 10.1271/bbb.120482
DO - 10.1271/bbb.120482
M3 - Article
C2 - 23221717
AN - SCOPUS:84871624539
SN - 0916-8451
VL - 76
SP - 2208
EP - 2213
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
IS - 12
ER -