Applying refinement to the use of mice and rats in rheumatoid arthritis research

Hawkins, Penny; Armstrong, Rachel; Boden, Tania; Garside, Paul; Knight, Katherine L.; Lilley, Elliot; Seed, Michael; Wilkinson, Michael; Williams, Richard O.

doi:10.1007/s10787-015-0241-4

Cited by 54 publications

(56 citation statements)

References 69 publications

(79 reference statements)

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“…Moreover, caliper-based measurements of pad thickness have been criticized for inconsistent reproducibility of measurements due to variability in paw placement [35]. Alternatively, plethysmometry and non-invasive imaging methods, such as infrared thermography, have been suggested as preferable replacement measures over the more traditional caliper-based paw thickness measurements [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Anti‐Inflammatory Effects of Cis‐9, Trans‐11 Conjugated Linoleic Acid to Celecoxib in the Collagen‐Induced Arthritis Model

Olson

Haas

Lor

et al. 2017

Lipids

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Cyclooxygenase (COX)-2 inhibitors, such as celecoxib, for chronic inflammatory disease are associated with adverse health events, while cis-9, trans-11 (c9t11) conjugated linoleic acid (CLA) is anti-inflammatory without adverse events attributed to pure intake. Mechanistically, celecoxib and c9t11 disrupt the arachidonic acid cascade; however, the equivalency of anti-inflammatory effects between these compounds is unknown. Therefore, to test the hypothesis that 0.5% dietary c9t11 reduces inflammation equivalently to a celecoxib dose intended to treat rheumatoid arthritis (RA; 5 mg/kg bw), arthritic mice received diets containing one of the following supplements: 1% corn oil (CO, w/w), 0.5% c9t11 (>91% purity) +0.5% CO, or 1% CO + 0.5, 5, or 50 mg/kg bw celecoxib, and were assessed for changes in arthritic severity over 6 weeks. Overall, arthritic severity in mice fed c9t11 was reduced (34%, P < 0.01) while celecoxib doses (0.5, 5, 50 mg/kg) reduced arthritic severity (16, 56, 48%, respectively) compared to CO-fed arthritic mice. Linear regression of the celecoxib dose-response showed 0.5% c9t11 (570 mg/kg bw) reduced arthritic severity equivalently to 1.5 mg/kg celecoxib. Interleukin-6 (IL-6) was increased in paws of arthritic mice fed CO compared to shams, but was decreased in arthritic groups fed 0.5% c9t11 and 5 mg/kg celecoxib, compared to arthritic mice fed CO (Ps ≤ 0.05). Additionally, paw and plasma IL-10 levels in arthritic mice were decreased by 5 mg/kg celecoxib, but were unaffected by c9t11 compared to CO. Results suggest dietary c9t11 may be an effective adjunct to COX-2 inhibition for treating chronic inflammation.

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Section: Discussionmentioning

confidence: 99%

A Comparison of the Anti‐Inflammatory Effects of Cis‐9, Trans‐11 Conjugated Linoleic Acid to Celecoxib in the Collagen‐Induced Arthritis Model

Olson

Haas

Lor

et al. 2017

Lipids

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“…Repeated dosing of both antigens was given two weeks later, while rats in both the normal control and arthritis groups received equal volume of saline instead. Paracetamol in a dose of 50 mg/kg/day was administered to all animals to alleviate the expected severe pain associated with the acute inflammation during the first week after induction of arthritis [31]. The protective effect of the parasitic antigens against AA was evaluated in terms of clinical assessment of the progression of arthritis and change in the body weight, biochemical estimates of inflammatory cytokines and histopathological examination of the inflamed joints.…”

Section: Methodsmentioning

confidence: 99%

“…The protective effect of the parasitic antigens against AA was evaluated in terms of clinical assessment of the progression of arthritis and change in the body weight, biochemical estimates of inflammatory cytokines and histopathological examination of the inflamed joints. Humane endpoints used during the study were: rapid weight loss of >20% of body weight that does not begin to reverse within 5 days, poor physical appearance in the form of scruffy fur and hunched body, severe paw ulceration with no signs of healing within 3 days, sledging and impaired ambulation which prevented animals from reaching food or water [31]. Two rats reached one of the humane endpoints, and they were euthanized by an over dose of thiopental sodium.…”

Section: Methodsmentioning

confidence: 99%

Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

et al. 2016

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A growing body of evidence supports the concept of helminths therapy in a variety of autoimmune diseases. Here, we aimed to investigate the protective effects of autoclaved Schistosoma mansoni antigen (ASMA) and Trichinella spiralis antigen (ATSA) on the clinical and immunopathological features of rheumatoid arthritis (RA). Adjuvant arthritis was induced by subcutaneous and intradermal injections of complete Freund’s adjuvant into the plantar surface of the right hind paw and the root of the tail, respectively. Rats were randomly assigned to serve as normal control, untreated arthritis, ASMA or ATSA-treated arthritis groups. Antigens were given by intradermal injection in two doses, two weeks apart. The development, progression of arthritic features, and the impact on animals’ gait and body weight were followed up for 4 weeks. The associated changes in serum cytokines (IL-17, IFN-γ and IL-10), joints’ histopathology and immunohistochemistry of Foxp3+ T regulatory cells (Tregs) were evaluated at the end of the study. Treatment with either ASMA or ATSA attenuated the progression of clinical features of polyarthritis, improved gait and body weight gain, reduced the elevated serum IL-17 and further increased both IFN-γ and IL-10. Histopathologically, this was associated with a remarkable regression of paws’ inflammation that was limited only to the subcutaneous tissue, and a significant increase in the number of Foxp 3+ cells versus the untreated arthritis group. In conclusion, both Schistosoma mansoni and Trichinella spiralis derived antigens exerted protective effect against adjuvant arthritis with better effect achieved by ASMA treatment. This anti-arthritic activity is attributed to upregulation of the Foxp3+ Tregs, with subsequent favorable modulation of both pro- and anti-inflammatory cytokines. The use of autoclaved parasitic antigens excludes the deleterious effects of imposing helminthic infection by using live parasites, which may pave the way to a new therapeutic modality in treating RA.

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“…On day 49 following disease induction, the mice paw swelling and arthritis index scores in the FMN-M group were signi cantly lower than those on day 21, indicating that FMN could signi cantly delay the disease progression of CIA. Additionally, animals in the RA group (without anti-RA drug treatment) suffered from weight reduction due to loss of appetite, disturbance of the immune system and persistent in ammation, which can also be used as an acute clinical signal to re ect the severity of the disease [25,26] . Thus, increased feeding is usually taken to counteract or prevent weight loss in RA animals [26] .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, animals in the RA group (without anti-RA drug treatment) suffered from weight reduction due to loss of appetite, disturbance of the immune system and persistent in ammation, which can also be used as an acute clinical signal to re ect the severity of the disease [25,26] . Thus, increased feeding is usually taken to counteract or prevent weight loss in RA animals [26] . However, the FMN treatment did, at least in part, prevent the weight loss of CIA mice in our experiment, with FMN-M displaying the strongest effect.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Activity of Formononetin in a Collagen-induced Arthritis Mouse Model ofRheumatoid Arthritis

Zhao

Wen-xue

et al. 2020

Preprint

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Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Although there are options for the treatment of RA, safer and more effective drugs are still being sought. Formononetin (FMN) is an isoflavonoid compound found in various plants, such as Astragalus propinquus Schischkin and Spatholobus suberectus. It has anti-tumor, anti-bacterial, anti-lipid peroxidation, and estrogen-like activities，and is a noteworthy compound for screening of anti-RA drugs. Methods: To investigate the anti-inflammatory effects of FMN in a collagen-induced arthritis (CIA) mouse model, thirty-six C57BL/6 mice were randomly divided into 6 groups: a healthy control group and 5 CIA groups. Arthritis was induced the CIA groups using chicken collagen type II. The CIA groups were divided in a control group (RA), a tripterygium glycosides (10 mg/kg body weight) treated group (TG), a low-dose (50 mg/kg) FMN group (FMN-L), a middle-dose(100mg/kg) FMN group (FMN-M), and a high-dose (200 mg/kg) FMN group (FMN-H). The control mice and CIA mice in the RA group were treated with an equal volume of 5% carboxymethylcellulose sodium. Drugs were delivered three times a week for four weeks, and the bodyweight, food-uptake, and swelling of the paws were monitored during the treatment process. Inflammatory cytokines and other biochemical indexes in the serum and joint tissues were analyzed, along with the expression levels of NF-κB pathway-related proteins (IκBα, p65, p-p65, TIPE2, and PCNP) in the spleen. Histopathological examinations were processed for the hind limbs. Results: FMN-M dramatically reduced the arthritis index in the CIA mice, inhibited the inflammatory cell infiltration, and prevented damage to the synovium and cartilage. Mechanistic studies suggested that FMN might reduce inflammation by inhibiting IκB-α degradation and by regulating the expression and release of NF-κB p65. Conclusions: These data suggest that FMN might be an active therapeutic agent for RA by preventing bone destruction, regulating inﬂammatory mediators, and suppressing NF-κB signaling pathways.

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Applying refinement to the use of mice and rats in rheumatoid arthritis research

Cited by 54 publications

References 69 publications

A Comparison of the Anti‐Inflammatory Effects of Cis‐9, Trans‐11 Conjugated Linoleic Acid to Celecoxib in the Collagen‐Induced Arthritis Model

A Comparison of the Anti‐Inflammatory Effects of Cis‐9, Trans‐11 Conjugated Linoleic Acid to Celecoxib in the Collagen‐Induced Arthritis Model

Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

Anti-inflammatory Activity of Formononetin in a Collagen-induced Arthritis Mouse Model ofRheumatoid Arthritis

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