title: Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses.
abstract: In the present study, we evaluated omega-3 polyunsaturated fatty acid (PUFA) (consisting of 20:5n-3 and 22:6n-3) properties on inflammation and nociception. Among the in vivo tests, writhing, formalin, and hot plate tests were conducted in mice, and carrageenan-induced paw edema, peritonitis, and Hargreaves tests were performed in rats. Following the carrageenan-induced edema, immunohistochemistry for tumor necrosis factor-α (TNF-α) was also carried out. We found that omega-3 PUFA treatment significantly decreased acetic acid-induced abdominal contortions as well as the first and second phases of the formalin test, which were reversed by naloxone. The carrageenan-induced rat paw edema was significantly reduced, along with neutrophil migration to the peritoneal cavity in the omega-3 PUFA treatment. In addition, there was a decrease in TNF-α immunostained cells in the inflamed paw with the omega-3 treatment compared with no omega-3. Withdrawal threshold in response to the thermal stimulation was significantly increased by the omega-3 treatment in the Hargreaves and hot plate tests. The in vitro studies (myeloperoxidase, lactate dehydrogenase, MTT cell viability and lipid peroxidation assays) were performed in human neutrophils. These studies showed that omega-3 treatment significantly decreased myeloperoxidase release, presented no cytotoxicity, and did not alter lipid peroxidation. Our study suggests that omega-3 PUFA anti-inflammatory and antinociceptive actions may involve inhibition of cyclooxygenases and microglial activation, leading to a reduced release of proinflammatory cytokines such as TNF-α, among other factors. The omega-3 PUFAs are potential candidates used alone or in combination with conventional nonsteroidal anti-inflammatory drugs, for the treatment of diseases where inflammation plays an important role.
authors.affiliation: Faculty of Medicine Estácio of Juazeiro do Norte-FMJ, Juazeiro do Norte, Brazil.
authors.forename: Maria Elizabeth Pereira
authors.initials: ME
authors.lastname: Nobre
authors.forename: Alyne Oliveira
authors.initials: AO
authors.lastname: Correia
authors.forename: Marília de Brito
authors.initials: Mde B
authors.lastname: Borges
authors.forename: Thayga Maria Araújo
authors.initials: TM
authors.lastname: Sampaio
authors.forename: Solon Arcoverde
authors.initials: SA
authors.lastname: Chakraborty
authors.forename: Danilo de Oliveira
authors.initials: Dde O
authors.lastname: Gonçalves
authors.forename: Gerly Anne de Castro
authors.initials: GA
authors.lastname: Brito
authors.forename: Luzia Kalyne Almeida Moreira
authors.initials: LK
authors.lastname: Leal
authors.forename: Cícero Francisco Bezerra
authors.initials: CF
authors.lastname: Felipe
authors.forename: Daniel Luna
authors.initials: DL
authors.lastname: Lucetti
authors.forename: Ricardo Mário
authors.initials: RM
authors.lastname: Arida
authors.forename: Glauce Socorro de Barros
authors.initials: GS
authors.lastname: Viana
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D002351:Carrageenan / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005557:Formaldehyde / Q000009:adverse effects; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D059225:Nociception / Q000187:drug effects; D010147:Pain Measurement; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D004281:Docosahexaenoic Acids; D002351:Carrageenan; D015118:Eicosapentaenoic Acid; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase