title: Potential Complementary Therapy for Adverse Drug Reactions to Sulfonamides: Chemoprotection Against Oxidative and Nitrosative Stress by TCM Constituents and Defined Mixtures.
abstract: OBJECTIVE
  Our working hypothesis is that bioactive phytochemicals that are important constituents of Traditional Chinese Medicine and their defined mixtures have potential as complementary therapy for chemoprotection against adverse drug reactions whose toxicity is not related to the pharmacological action of the drug but where oxidative and nitrosative stress are causative factors.
  
  
  METHODS
  In this investigation we measured cytotoxicity, lipid peroxidation, protein carbonylation and ROS/NOS-mediated changes in the disulfide proteome of Jurkat E6.1 cells resulting from exposure to sulfamethoxazole N-hydroxylamine with or without pre-treatment with low µM concentrations of baicalein, crocetin, resveratrol and schisanhenol alone and in defined mixtures to compare the ability of these treatment regimens to protect against ROS/RNS toxicity to Jurkat E6.1 cells in culture.
  
  
  RESULTS
  Each of the Traditional Chinese Medicine constituents and defined mixtures tested had significant chemoprotective effects against the toxicity of ROS/RNS formed by exposure of Jurkat E6.1 cells to reactive metabolites of sulfamethoxazole implicated as the causative factors in adverse drug reactions to sulfa drugs used for therapy. At equimolar concentrations, the defined mixtures tended to be more effective chemoprotectants overall than any of the single constituents against ROS/RNs toxicity in this context.
  
  
  CONCLUSIONS
  At low µM concentrations, defined mixtures of TCM constituents that contain ingredients with varied structures and multiple mechanisms for chemoprotection have excellent potential for complementary therapy with sulfa drugs to attenuate adverse effects caused by oxidative/nitrosative stress. Typically, such mixtures will have a combination of immediate activity due to short in vivo half-lives of some ingredients cleared rapidly following metabolism by phase 2 conjugation enzymes; and some ingredients with more prolonged half-lives and activity reliant on phase 1 oxidation enzymes for their metabolic clearance. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
authors.affiliation: Department of Pathology and Laboratory Medicine, Schulich Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON, Canada.
authors.forename: Lee
authors.initials: L
authors.lastname: Zhang
authors.forename: Dao-Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Xue Yan
authors.initials: XY
authors.lastname: Xia
authors.forename: Cindy
authors.initials: C
authors.lastname: Yip
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Rieder
authors.forename: John Richard
authors.initials: JR
authors.lastname: Bend
mesh_terms: D000529:Complementary Therapies / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D015227:Lipid Peroxidation / Q000187:drug effects; D008516:Medicine, Chinese Traditional / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013420:Sulfamethoxazole / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; C059873:sulfamethoxazole hydroxylamine; D013420:Sulfamethoxazole