Thioctic acid protects against carrageenan-induced acute inflammation in rats by reduction in oxidative stress, downregulation of COX-2 mRNA and enhancement of IL-10 mRNA.
Free radicals are highly reactive species which played an important role in the pathogenesis of acute inflammation. In this study, the protective role of the known antioxidant, thioctic acid, in carrageenan-induced acute inflammation in rats was assessed and was compared to the reference non-steroidal anti-inflammatory drug (NSAID) indomethacin. In addition, the roles of oxidative stress, nitric oxide (NO), inducible cyclooxygenase isoform (COX-2) and interleukin (IL)-10 mRNA expressions in thioctic acid-induced effects were also investigated. Inflammation was induced by injection of 0.1 ml of 1.5% carrageenan into the plantar side of right hind paws of the rats. Thioctic acid (50, 100 or 200 mg/kg), indomethacin (10 mg/kg), DMSO and saline were injected i.p. 2 h before carrageenan injection. The percentage increase in paw weight was calculated. Frozen hind paw were used for estimation of lipid peroxides (MDA), NO, GSH, COX-2 and IL-10 mRNA expression. Formalin fixed hind paw were used for histopathological examination. Thioctic acid (200 mg/kg) reduced both paw edema formation and lymphocytes infiltration more significant than indomethacin itself: Both thioctic acid and indomethacin reduced paw MDA and NO formation. In addition, both agents restored the depleted GSH contents in the paw. Thioctic acid decreased the elevated COX-2 mRNA while indomethacin, failed. Furthermore, thioctic acid increased IL-10 mRNA expression while indomethacin decreased its expression. Thioctic acid exhibited a potent anti-inflammatory effect on carrageenan-induced inflammation compared to the NSAID indomethacin. The mechanisms of thioctic induced protection were proved to be due to reduction of NO, MDA, COX-2 mRNA and induction of GSH, IL-10 mRNA.
El-Shitany
Nagla A
NA
Department of Pharmacology & Toxicology, Collage of Pharmacy, Tanta University, Tanta, Egypt. nagla_fouad@yahoo.com
El-Masry
Sanaa A
SA
El-Ghareib
Mahmoud A
MA
El-Desoky
Karema
K
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D051546:Cyclooxygenase 2 / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10; D009569:Nitric Oxide; D008063:Thioctic Acid; D002351:Carrageenan; D051546:Cyclooxygenase 2; D007213:Indomethacin