Thiamine and riboflavin inhibit production of cytokines and increase the anti-inflammatory activity of a corticosteroid in a chronic model of inflammation induced by complete Freund’s adjuvant

• Published in: Pharmacological reports 2017-10, Vol.69 (5), p.1036-1043
• Main Authors: Menezes, Raquel R., Godin, Adriana M., Rodrigues, Felipe Fernandes, Coura, Giovanna M.E., Melo, Ivo S.F., Brito, Ana Mercy S., Bertollo, Caryne M., Paulino, Tony P., Rachid, Milene A., Machado, Renes R., Coelho, Márcio M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - therapeutic use; Chronic Disease; Corticosteroids; Cytokines; Cytokines - genetics; Cytokines - metabolism; Dexamethasone - administration & dosage; Dexamethasone - therapeutic use; Drug Safety and Pharmacovigilance; Drug Therapy, Combination; Female; Freund's Adjuvant - therapeutic use; Gene Expression Regulation - drug effects; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Original Article; Pharmacotherapy; Pharmacy; Rats; Rats, Sprague-Dawley; Riboflavin; Riboflavin - administration & dosage; Riboflavin - pharmacology; Thiamine; Thiamine - administration & dosage; Thiamine - pharmacology
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2017.04.011

The effects induced by thiamine and riboflavin, isolated or in association with corticosteroids, in models of chronic inflammation are not known. Thus, we evaluated the effect induced by these B vitamins, isolated or in association with dexamethasone, on the mechanical allodynia, paw edema and cytokine production induced by complete Freund’s adjuvant (CFA) in rats. Chronic inflammation was induced by two injections of CFA. Nociceptive threshold, paw volume and body temperature were evaluated for 21days. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) contents were determined in paw tissue. Riboflavin (125, 250 or 500mg/kg) or thiamine (150, 300 or 600mg/kg) were administered per os (po), twice daily. Dexamethasone (0.5mg/kgday, po) was administered every three days. CFA induced long lasting mechanical allodynia and paw edema. Elevation of body temperature was observed for a short period. Riboflavin reduced neither paw edema nor mechanical allodynia. Thiamine did not change paw edema, but partially inhibited mechanical allodynia. Riboflavin (500mg/kg) and thiamine (600mg/kg) exacerbated the anti-inflammatory activity of dexamethasone. Riboflavin, thiamine and dexamethasone reduced TNF-α and IL-6 production. The association of dexamethasone with thiamine induced greater inhibition of IL-6 production when compared with that induced by dexamethasone. Riboflavin and thiamine exacerbate the anti-inflammatory activity of dexamethasone and reduce production of TNF-α and IL-6.