Kwiecień Brunon, Dudek Magdalena, Bilska-Wilkosz Anna, Knutelska Joanna, Bednarski Marek, Kwiecień Inga, Zygmunt Małgorzata, Iciek Małgorzata, Sokołowska-Jeżewicz Maria, Sapa Jacek, Włodek Lidia
Department of Chemistry and Physics, Hugon Kołłątaj University of Agriculture, Kraków, Poland.
Postepy Hig Med Dosw (Online). 2013 Apr 24;67:331-8. doi: 10.5604/17322693.1046290.
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.
在哺乳动物中，硫辛酸（LA）及其还原形式二氢硫辛酸（DHLA）作为多酶复合物的辅助因子，催化α-酮酸的脱羧反应。此外，LA还被用作治疗包括炎症性疾病在内的多种疾病的药物。本研究的目的是检测LA代谢产物的抗炎特性。
材料/方法：本文报道了2,4-双甲基硫代丁酸（BMTBA）和四降二氢硫辛酸（四降-DHLA）的化学合成。BMTBA是LA的生物转化产物之一，而四降-DHLA是DHLA的类似物。通过1H NMR确认了这些化合物的结构同一性。在小鼠中评估了这些化合物的抗炎活性。为此，应用了酵母聚糖诱导的腹膜炎和角叉菜胶诱导的后爪水肿动物模型。
结果/结论：所得结果表明，在接受BMTBA（10、30、50mg/kg）的组中，酵母聚糖诱导的腹膜炎30分钟时测得的早期血管通透性受到显著抑制。在接受BMTBA（50mg/kg）和四降-DHLA（50mg/kg）的组中，酵母聚糖诱导的腹膜炎4小时时测得的中性粒细胞早期浸润受到抑制。结果表明，在接受BMTBA（50、100mg/kg）和四降-DHLA（30、50mg/kg）的组中，爪水肿的增加受到显著抑制。总之，本研究清楚地表明，BMTBA和四降-DHLA均能够作为抗炎剂发挥作用。这是第一项在体内研究LA代谢产物抗炎特性的研究。
