title: High-dose chlorogenic acid induces inflammation reactions and oxidative stress injury in rats without implication of mast cell degranulation.
abstract: BACKGROUND
  Chlorogenic acid (CA) exits widely in those Chinese herbal injections that have antibacterial and antiphlogistic effects and belongs to the ethnopharmacological family of medicines. Chinese herbal injections containing high levels of CA have been reported to increase the adverse drug reactions, but the mechanism for which is still unclear. In this study, we investigated the mechanism of the CA derived adverse drug reactions.
  
  
  OBJECTIVE
  The present study was to explore the potential role of CA in initiating inflammatory reaction and the underlying mechanism.
  
  
  METHODS
  Male Wistar rats were treated with different dosages of CA for different time period. The variables examined included microcirculation by intravital microscopy, histology of ileum tissue, expression of adhesion molecules CD11b and CD18 on leukocytes by flow cytometry, myeloperoxidase activity and maleic dialdehyde content in ileum tissue by spectrophotometry, activity of superoxide dismutase and catalase in serum by ELISA, and expression of NADPH oxidase subunits by PCR and Western blot.
  
  
  RESULTS
  High-dose CA increased the number of adherent leukocytes, generation of peroxides in the venular walls and induced albumin leakage from mesentery venules. High-dose CA induced changes also included an increase in maleic dialdehyde, myeloperoxidase, inflammatory cytokines and NADPH oxidase activities, and a decline in activity of superoxide dismutase and catalase.
  
  
  CONCLUSIONS
  High-dose, but not Low-dose CA induced inflammation reaction, and in this process an imbalance between oxidant and antioxidant mechanism may be involved, providing more information for better understanding the rationale behind the adverse effects of CA.
authors.affiliation: Department of Pathology, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Du
authors.forename: Cheng
authors.initials: C
authors.lastname: Chang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Chuan-She
authors.initials: CS
authors.lastname: Wang
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.forename: Peng-Tao
authors.initials: PT
authors.lastname: Li
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000097:blood; D015550:Cell Degranulation / Q000187:drug effects; D002726:Chlorogenic Acid / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D007082:Ileum / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D008643:Mesentery / Q000098:blood supply*; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012709:Serum Albumin / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014699:Venules / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D002726:Chlorogenic Acid; D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1