title: In vivo anti-inflammatory activity of lipoic acid derivatives in mice.
abstract: BACKGROUND
  In mammals lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) function as cofactors for multienzymatic complexes catalyzing the decarboxylation of α-ketoacids. Moreover, LA is used as a drug in a variety of diseases including inflammatory diseases. The aim of the study was to examine anti-inflammatory properties of LA metabolites.
  
  
  METHODS
  The present paper reports the chemical synthesis of 2,4-bismethylthio-butanoic acid (BMTBA) and tetranor-dihydrolipoic acid (tetranor-DHLA). BMTBA is one of the biotransformation products of LA, while tetranor-DHLA is an analogue of DHLA. Structural identity of these compounds was confirmed by 1H NMR. These compounds were assessed for their anti-inflammatory activity in mice. For this purpose, the zymosan-induced peritonitis and the carrageenan-induced hind paw edema animal models were applied.
  
  
  CONCLUSIONS
  The obtained results indicated that the early vascular permeability measured at 30 min of zymosan-induced peritonitis was significantly inhibited in groups receiving BMTBA (10, 30, 50 mg/kg). The early infiltration of neutrophils measured at 4 hours of zymosan-induced peritonitis was inhibited in the group receiving BMTBA (50 mg/kg) and tetranor-DHLA (50 mg/kg). The results indicated that the increase in paw edema was significantly inhibited in the groups receiving BMTBA (50, 100 mg/kg) and tetranor-DHLA (30, 50 mg/kg). In summary, the present studies clearly demonstrated that both BMTBA and tetranor-DHLA were able to act as anti-inflammatory agents. This is the first study examining in vivo the anti-inflammatory properties of LA metabolites.
authors.affiliation: Department of Chemistry and Physics, Hugon Kołłątaj University of Agriculture, Kraków, Poland.
authors.forename: Brunon
authors.initials: B
authors.lastname: Kwiecień
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
authors.forename: Anna
authors.initials: A
authors.lastname: Bilska-Wilkosz
authors.forename: Joanna
authors.initials: J
authors.lastname: Knutelska
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.forename: Inga
authors.initials: I
authors.lastname: Kwiecień
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Iciek
authors.forename: Maria
authors.initials: M
authors.lastname: Sokołowska-Jeżewicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.forename: Lidia
authors.initials: L
authors.lastname: Włodek
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D002087:Butyrates / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy*; D013438:Sulfhydryl Compounds / Q000494:pharmacology* / Q000633:toxicity; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D023382:Toxicity Tests, Acute; D015054:Zymosan
chemical_list: C583134:2,4-bismethylthiobutanoic acid; D000893:Anti-Inflammatory Agents; D002087:Butyrates; D013438:Sulfhydryl Compounds; C583135:tetranor-dihydrolipoic acid; D008063:Thioctic Acid; D002351:Carrageenan; D015054:Zymosan