Fish Oil and Adjuvant-Induced Arthritis: Inhibitory Effect on Leukocyte Recruitment
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Fish Oil and Adjuvant-Induced Arthritis: Inhibitory Effect on Leukocyte Recruitment Camila Fernanda Estevão-Silva,1 Franciele Queiroz Ames,1 Francielli Maria de Souza Silva-Comar,1 Raquel Kummer,1 Rafael Prizon Tronco,1 Roberto Kenji Nakamura Cuman,1 and Ciomar Aparecida Bersani-Amado1,2
Abstract—Fish oil, a rich source of n-3 fatty acids, has been studied for its beneficial effects in many diseases. Recent studies have shown the robust anti-inflammatory activity of fish oil (FO), when administered orally to rats, in models of acute inflammation. Herein, we investigated if treatment with fish oil preparation (FOP) could interfere with the recruitment of leukocytes into the joint cavity of arthritic rats. We also evaluated the effect of treatment on rolling behavior and leukocyte adhesion in vivo and on leukocyte chemotaxis in vitro. Treatment with FOP (75, 150, and 300 mg/kg) initiated on the day of induction of arthritis (day 0) and maintained for 21 days reduced the total number of leukocytes recruited into the joint cavity, the number of rolling and adhered leukocytes in arthritic rats, and leukocyte migration in response to stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and leukotriene B4 (LTB4). Together, our data provide evidence that FOP plays an important inhibitory role in the recruitment of leukocytes into the joint cavity of arthritic rats. KEY WORDS: fish oil; leukocyte migration; arthritis; microcirculation; time course.
INTRODUCTION Fish oil, a rich source of n-3 fatty acids, has been studied for its beneficial effects in many diseases, including inflammatory and autoimmune diseases [1–6]. Evidence indicates that dietary supplementation with fish oil containing standard concentrations of docosahexaenoic acid (DHA, 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n3) is associated with a reduction in the number of swollen joints and pain relief, with the possibility of reducing the dose of anti-inflammatory drugs for the therapy of rheumatoid arthritis [7, 8]. Furthermore, supplementation with n-3 fatty acids has gained attention as an important adjuvant therapy in these disease conditions, especially because pharmacotherapy with anti-inflammatory drugs is associated with adverse effects [9]. In most of these studies, fish oil (FO) was 1
Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil 2 To whom correspondence should be addressed at Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil. E-mail: [email protected]
administered for several days or months, suggesting that the clinical improvement was associated with an increase in n-3 fatty acids in membrane lipids [10–14]. Once incorporated into the phospholipids of the cellular membrane, fish oil can affect cell functions in a variety of ways, i.e., by affecting membrane fluidity, the amount and type of eicosanoids produced, the activity of components of signal transduction systems, immune cell populations, and gene expression [12, 15–17]. A recent study
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