title: Involvement of NADPH oxidase in high-dose phenolic acid-induced pro-oxidant activity on rat mesenteric venules.
abstract: In the present study, we investigated the potential role of phenolic acids in initiating oxidative damage to microvascular endothelial cells and the underlying mechanism mediating the pro-oxidant action. Male Wistar rats received high doses of phenolic acid [caffeic acid (CA), salvianolic acid B (SAB), chlorogenic acid (ChA) or ferulic acid (FA)]. The creation of reactive oxygen species in mesenteric microcirculation endothelial cells and adherent leukocytes along with venules were assessed using intravital microscopy. The expression levels of NADPH oxidase subunits (Nox4 and p22phox) in terminal ileum tissues were determined by western blot analysis. Intravenous injection of high-dose ChA or CA (7 mg/kg) markedly increased the peroxide production in the venular walls and upregulated the protein expression levels of Nox4 and p22phoxin the ileum tissues, while the same dose of CA and SAB made no difference within the observation period. No changes were observed in the number of leukocytes adhering to the venular walls. High-dose ChA and FA led to an imbalance between the oxidant and antioxidant mechanism by boosting the expression levels of NADPH oxidase. Thus, we clarified the rationale behind the adverse effects of a herbal injection containing high levels of phenolic acid compounds.
authors.affiliation: Medical and Electronic Experimental Center, The Traditional Chinese Medicine Hospital of Shijiazhuang Affiliated to Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Du
authors.affiliation: School of Chemical Engineering, Shijiazhuang University, Shijiazhuang, Hebei 050035, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Medical and Electronic Experimental Center, The Traditional Chinese Medicine Hospital of Shijiazhuang Affiliated to Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Jian-Jing
authors.initials: JJ
authors.lastname: Yao
authors.affiliation: The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Hao
authors.affiliation: Medical and Electronic Experimental Center, The Traditional Chinese Medicine Hospital of Shijiazhuang Affiliated to Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050051, P.R. China; The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Zhao
keywords: NADPH oxidase; drug safety; mesenteric microcirculation; phenolic acid; reactive oxygen species