Anti-inflammatory Effects of Vitamin E on Adjuvant-Induced Arthritis in Rats

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Anti-inflammatory Effects of Vitamin E on Adjuvant-Induced Arthritis in Rats Mateus Fortes Rossato,1,4 Carin Hoffmeister,2 Raquel Tonello,1 Ana Paula de Oliveira Ferreira,1 and Juliano Ferreira1,2,3

Abstract—Vitamin E (vit-E) is a lipophilic antioxidant, and its anti-inflammatory activity is still not full characterized. Thus, our goal was to investigate the anti-inflammatory effect of repeated vit-E treatment in the arthritis induced by the intraplantar injection of complete Freund’s adjuvant (CFA). We observed an increase in arthritis scores, interleukin-1β and H2O2 levels, neutrophil and macrophage infiltration, thermal hyperalgesia, mechanical allodynia, and loss of function induced by intraplantar CFA injection. These effects were unaltered after 1 day, partially reversed after 3 days, and inhibited after 9 days after vit-E treatment. Furthermore, the concentration of vit-E was reduced and that of tumor necrosis factoralpha was increased in the CFA-injected paw. Both effects were reversed from 1 to 9 days after vit-E treatment. However, vit-E treatment did not alter CFA-induced edema at any time. Thus, vit-E treatment produced an anti-inflammatory effect of slow onset in CFA, which demonstrates a disease-modifying drug profile. KEY WORDS: TNFα; IL1β; myeloperoxidase; NAGase; hydrogen peroxide.

vit-E, and it confers beneficial effects against a large number of diseases, such as cardiovascular and neurodegenerative disorders [4, 5]. Furthermore, vit-E reportedly exerts an antiinflammatory effect against several inflammatory diseases, such as hypersensitivity reactions, airway inflammation, and several types of arthritis [6]. Patients with several types of arthritis exhibit reduced levels of vit-E in the plasma and synovial fluid [7–9]. Also, it was demonstrated that adjuvant-induced arthritis increased serum markers of oxidative stress, some restored by vit-E chronic supplementation [10], while another study showed that prior vit-E deprivation exacerbate some inflammatory markers of collagen-induced arthritis [11]. Despite it, none evaluated non-nociceptive/behavioral alteration, the most debilitating symptoms or, arthritis and the causes for patients to go for medical help. However, clinical trials of vitamin E in the treatment of arthritis have yielded contradictory findings [12, 8]. Notably, a prospective placebo-controlled double-blind trial indicated that repeated vit-E treatment reduced pain parameters but not clinical indices of inflammation in rheumatoid arthritis patients [13]. In arthritis, a simple analgesic effect must be distinguished from an antiinflammatory effect as analgesics alleviate pain but do

INTRODUCTION Vitamin E (vit-E) is the generic name for the phenolic compounds α, β, γ, and Δ tocopherol, which consist of a chroman head and a phytyl tail. These compounds are lipophilic constituents of foods such as fish, seeds, and cereals [1]. In mammals, vit-E is found in several compartments, including peripheral and central tissues, cerebrospinal fluid, and plasma, occurring predominantly as α