title: Water-soluble phenol TS-13 combats acute but not chronic inflammation.
abstract: OBJECTIVE
  This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation.
  
  
  METHODS
  Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis. The effects of TS-13 treatment were estimated by changes in the intensity of inflammation (paw edema, liver infiltration, animal survival, exudation, and clinical score of arthritis) and by the effects on reactive oxygen species (ROS) generation by leukocytes from peripheral blood and inflammatory exudates.
  
  
  RESULTS
  We found the significant increase in expression of mRNA, content of protein and activity of a well-characterized Nrf2 target enzyme glutathione S-transferase P1, as well as nuclear extract protein binding to the ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13 markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte number and volume density of liver infiltrates in the systemic zymosan-induced inflammation model, and increased mice survival after lipopolysaccharide-induced septic shock. However, TS-13 administration did not influence cell and protein exudation into air pouches and suppressed clinical manifestation of collagen-induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the generation of ROS by leukocytes in all inflammation models.
  
  
  CONCLUSIONS
  The data suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more prominent against acute innate-mediated inflammation than chronic immune inflammation. This narrows the potential therapeutic efficacy of ARE inducers in inflammation treatment.
authors.affiliation: Center of Clinical and Experimental Medicine, Novosibirsk, Russia, lemen@centercem.ru.
authors.forename: Elena
authors.initials: E
authors.lastname: Menshchikova
authors.forename: Victor
authors.initials: V
authors.lastname: Tkachev
authors.forename: Anna
authors.initials: A
authors.lastname: Lemza
authors.forename: Tatyana
authors.initials: T
authors.lastname: Sharkova
authors.forename: Natalya
authors.initials: N
authors.lastname: Kandalintseva
authors.forename: Valentin
authors.initials: V
authors.lastname: Vavilin
authors.forename: Olga
authors.initials: O
authors.lastname: Safronova
authors.forename: Nikolay
authors.initials: N
authors.lastname: Zenkov
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D061745:Antioxidant Response Elements / Q000276:immunology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002351:Carrageenan; D002908:Chronic Disease; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005528:Foot / Q000473:pathology; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D000072019:Kelch-Like ECH-Associated Protein 1; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000276:immunology; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy*; D012995:Solubility; D013886:Thiosulfonic Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014867:Water / Q000737:chemistry; D015054:Zymosan
chemical_list: C553321:3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonic acid; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013886:Thiosulfonic Acids; D014867:Water; D002351:Carrageenan; D015054:Zymosan; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat