In Vivo Anti-inflammatory Activity of Lipoic Acid Derivatives in Mice

• Main Authors: Brunon Kwiecień, Magdalena Dudek, Anna Bilska-Wilkosz, Joanna Knutelska, Marek Bednarski, Inga Kwiecień, Małgorzata Zygmunt, Małgorzata Iciek, Maria Sokołowska-Jeżewicz, Jacek Sapa, Lidia Włodek
• Format: Article
• Language: English
• Published: Index Copernicus International S.A. 2013-04-01
• Series: Postępy Higieny i Medycyny Doświadczalnej
• Subjects: Hydrogen Sulfide; anti-inflammatory properties; Zymosan; Carrageenan; 2; 4-(bismethylthio)-butanoic acid; tetranor-dihydrolipoic acid; dihydrolipoic acid; lipoic acid
• Online Access: http://journals.indexcopernicus.com/fulltxt.php?ICID=1046290

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.Material/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.Results/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.