Anti-inflammatory and analgesic effects of atorvastatin in a rat model of adjuvant-induced arthritis

Barsante, Michele M.; Roffê, Ester; Yokoro, C.M.; Tafuri, Wagner Luiz; Souza, Danielle G.; Pinho, Vanessa; Castro, Maria Salete de A; Teixeira, Mauro M.

doi:10.1016/j.ejphar.2005.05.005

Cited by 142 publications

(96 citation statements)

References 46 publications

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“…Thus, the hypernociception observed in our study may be the result of the intrinsic immune response from the 7 th to the 10 th day after immunization. Cytokines were found to mediate hypernociception in a carrageenan-induced inflammatory model of hyperalgesia 10 and chemokines (chemotactic cytokines) seem to be involved in the hypernociception elicited by an experimental model of arthritis 24 . Chemokines are also important in MS 25,26 and they are involved in many pathways of pain 27 .…”

Section: Discussionmentioning

confidence: 96%

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Rodrigues

Sachs

Teixeira

2009

Arq. Neuro-Psiquiatr.

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-Background:Pain is an important clinical manifestation in multiple sclerosis (MS) patients, though it has been neglected in clinical and experimental researches. Objective: To investigate the nociceptive response in MOG 35-55 experimental autoimmune encephalomyelitis (EAE)-induced mice. Method: EAE was induced in 8 to 10 week old C57BL/6 female mice with an emulsion of MOG , Complete Freund Adjuvant, Mycobacterium tuberculosis H37 RA and pertussis toxin. Nociception was evaluated by the von Frey filaments method. A clinical scale ranging from 0 to 15 was used to assess motor impairment. Results: Clinical evidence of disease started at day 10 and peaked at day 14 after immunization. Thereafter, there was no worsening of symptoms until day 26. The EAE-induced mice presented reduced pressure threshold at days 7 th and 10 th after immunization and before the onset of clinical motor signs. Conclusion: The hypernociception found validates MOG 35-55 EAE as a model for the study of pain in multiple sclerosis.KEY WORDS: multiple sclerosis; experimental autoimmune encephalomyelitis, hyperalgesia, mechanical hypernociception. hipernocicepção mecânica em encefalomielite autoimune experimentalResumo -Introdução: Dor é uma manifestação importante em pacientes com esclerose múltipla (EM), mas que tem sido negligenciada na pesquisas clínica e experimental. Objetivo: Investigar a resposta nociceptiva de camundongos com encefalomielite autoimune experimental (EAE) induzida por MOG . Método: A EAE foi induzida em camundongos C57BL/6 fêmeas de 8-10 semanas com emulsão contendo MOG 35-55 , Adjuvante Completo de Freund, Mycobacterium tuberculosis cepa H37 RA e toxina pertussis. A nocicepção foi medida pelo método de filamentos de von Frey. Uma escala clínica variando de 0 a 15 foi utilizada para avaliar a debilidade motora dos animais. Resultados: Os sinais clínicos da doença iniciaram-se no dia 10 e a gravidade máxima foi alcançada no dia 14 após a imunização. Não houve piora dos sintomas até o dia 26. Os camundongos induzidos com EAE apresentaram diminuição do limiar de pressão nos dias 7 e 10 após a imunização e antes do início dos sinais motores. Conclusão: A hipernocicepção verificada valida a EAE induzida por MOG 35-55 como um modelo para estudos de dor em esclerose múltipla. PALAVRAS-CHAVE: esclerose múltipla; encefalomielite autoimune experimental, hiperalgesia; hipernocicepção mecânica.

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Section: Discussionmentioning

confidence: 96%

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Rodrigues

Sachs

Teixeira

2009

Arq. Neuro-Psiquiatr.

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“…A more recent study showed no preventive or curative effects of atorvastatin, rosuvastatin, or simvastatin in murine collagen-induced arthritis (40). In a rat model of AIA, atorvastatin administered orally at a daily dosage of 1-10 mg/kg was shown to inhibit arthritis (41).…”

Section: Discussionmentioning

confidence: 99%

Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant‐induced arthritis

Haruna

Morita

Yada

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate the effect of statins on vascular dysfunction in rat adjuvant-induced arthritis (AIA).Methods. Fluvastatin (5 mg/kg/day) was administered orally to rats with AIA, for 21 days after the onset of arthritis. The vasodilatory response to acetylcholine of aortic rings isolated from rats with AIA that were not treated or were treated with fluvastatin and from normal rats was determined. The amounts of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine in aortas were measured by Western blotting. In vitro and in situ superoxide production in aortas was evaluated based on fluorogenic oxidation of dihydroethidium to ethidium. Expression of NAD(P)H components and endothelial nitric oxide synthase (eNOS) in aortas was examined by real-time reverse transcriptase-polymerase chain reaction and Western blotting. Serum levels of tetrahydrobiopterin, a critical eNOS cofactor, were determined by high-performance liquid chromatography.Results. Fluvastatin reversed endothelial dysfunction in AIA without affecting the clinical severity of arthritis or serum cholesterol concentration. Fluvastatin reduced the amounts of HNE and nitrotyrosine in the aorta, and the levels of superoxide expressed in endothelial cells and smooth muscle cells in the tissue, in rats with AIA. NADH-or L-arginine-induced superoxide production was not observed in the aortic samples from fluvastatin-treated rats with AIA. Fluvastatin decreased the levels of expression of messenger RNA for p22phox, a NAD(P)H oxidase component, in the aortas of rats with AIA, but did not affect the expression of eNOS. Serum levels of tetrahydrobiopterin were significantly reduced in rats with AIA, and were increased by administration of fluvastatin.Conclusion. Our findings demonstrate that fluvastatin has potent vascular protective effects in AIA and provide additional scientific rationale for the use of statins to reduce cardiovascular mortality in patients with rheumatoid arthritis.

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“…Female Holtzman rats were immunized with a single s.c. injection of 0.2 ml mineral oil-water emulsion (10:1, v/v) containing 400 mg dried Mycobacterium butyricum into the dorsal root of the tail at day 0, as previously described (28). Control animals were s.c. injected with a single dose of 0.2 ml mineral oil-water emulsion (10:1) without M. butyricum in the same site.…”

Section: Rat Adjuvant-induced Arthritismentioning

confidence: 99%

“…Control animals were s.c. injected with a single dose of 0.2 ml mineral oil-water emulsion (10:1) without M. butyricum in the same site. Rats were treated daily from day 10 to 16 (28,29) with AVE 0991 (3 mg/kg, orally, 0.5 ml) or vehicle (10 mM KOH in 0.9% NaCl). Periarticular edema was evaluated daily, and tissue neutrophil infiltration, production of IL-1b and CXCL1, and histopathological analysis were performed at day 16 and the animals were killed under sodium thiopental anesthesia (40 mg/kg).…”

Section: Rat Adjuvant-induced Arthritismentioning

confidence: 99%

Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

Sachs¹

2010

The Journal of Immunology

155

107

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Activation of the renin-angiotensin (Ang) system induces inflammation via interaction between Ang II and type 1 receptor on leukocytes. The relevance of the new arm of the renin-Ang system, namely Ang-converting enzyme-2/Ang-(1–7)/Mas receptor, for inflammatory responses is not known and was investigated in this study. For this purpose, two experimental models were used: Ag-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Male C57BL/6 wild-type or Mas−/− mice were subjected to AIA and treated with Ang-(1–7), the Mas agonist AVE 0991, or vehicle. AdIA was performed in female rats that were given AVE 0991 or vehicle. In wild-type mice, Mas protein is expressed in arthritic joints. Administration of AVE 0991 or Ang-(1–7) decreased AIA-induced neutrophil accumulation, hypernociception, and production of TNF-α, IL-1β, and CXCL1. Histopathological analysis showed significant reduction of inflammation. Mechanistically, AVE 0991 reduced leukocyte rolling and adhesion, even when given after Ag challenge. Mas−/− mice subjected to AIA developed slightly more pronounced inflammation, as observed by greater neutrophil accumulation and cytokine release. Administration of AVE 0991 was without effect in Mas−/− mice subjected to AIA. In rats, administration of AVE 0991 decreased edema, neutrophil accumulation, histopathological score, and production of IL-1β and CXCL1 induced by AdIA. Therefore, activation of Mas receptors decreases neutrophil influx and cytokine production and causes significant amelioration of arthritis in experimental models of arthritis in rats and mice. This approach might represent a novel therapeutic opportunity for arthritis.

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Anti-inflammatory and analgesic effects of atorvastatin in a rat model of adjuvant-induced arthritis

Cited by 142 publications

References 46 publications

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant‐induced arthritis

Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

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