Structural efficacy of NSAIDs, COX-2 inhibitor and glucocorticoid compared with TNFα blocker: a study in adjuvant-induced arthritis rats

Verhoeven, Frank; Prati, Clément; Totoson, Perle; Bordy, Romain; Wendling, Daniel; Demougeot, Céline

doi:10.1093/rheumatology/key444

Cited by 6 publications

(5 citation statements)

References 18 publications

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“…It is also encouraging that with the continuous injection of uricase into the joints, the symptoms of the experimental animals improved significantly, including reduced joint swelling, decreased temperature and decreased TNFα and IL-1β level. This treatment effect is similar to the treatment of arthritis by nonsteroidal anti-inflammatory drugs(NSAIDS) [29], so uricase can inhibit or alleviate urate-induced inflammation.…”

Section: Discussionmentioning

confidence: 85%

The effect of uricase on monosodium urate (MSU) crystallization, IL-1β and TNFα in monosodium urate-induced arthritis

Chen

Liang²,

Wang³

et al. 2020

Preprint

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Background : Although the symptoms of gouty arthritis could be controlled by clinical methods, it is often impossible to remove tophi from joints that cause acute gouty arthritis. Methods : In study, we injected a suspension of MSU into the knee joint of chicken, and then injected uricase solution into the joint after 4, 8 and 12 hours. Since the beginning of the experiment, we monitored the circumference of the diseased joint and local temperature change. Computer tomography(CT) examination was performed to examine the MSU in the knee joints and then measured the levels of TNFα and IL-1β in synovial fluid. Chicken knee joint fluid was collected under polarized light microscope to observe the condition of the crystals and measured the weight of MSU residued in synovial fluid. Finally, the chicken knee joint was dissected and the joint synovium was sliced. Results : The results showed that injection of MSU suspension into chicken knee joint, significantly increased IL-1β, TNFα levels (p<0.01), circumference of the joint (p<0.05) and the local skin temperature (p<0.05). Moreover, analysis of the joint fluid and synovial slice under the polarized light microscope revealed that crystals significantly reduced. Compared with groupⅡ(control group), the residual weight of MSU in the joint fluid of group Ⅲ and group Ⅳ is very small(p<0.05), but there is no significant difference between group Ⅲ and group Ⅳ(p＞0.05). Conclusions : The comprehensive analysis shows that the reaction process between uricase and MSU is similar to that uric acid. Therefore, it provides a new way for clinical treatment of acute gouty arthritis with fewer side effects and significant reduction in the frequency of attacks.

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Section: Discussionmentioning

confidence: 85%

The effect of uricase on monosodium urate (MSU) crystallization, IL-1β and TNFα in monosodium urate-induced arthritis

Chen

Liang²,

Wang³

et al. 2020

Preprint

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“…However, although the bacteria are dead, the principle of antigenic peptide presentation remains the essential element of this model together with the production of inflammatory factors. Moreover, this model is characterized by an ankylosis of the tail, comparable to the spinal ankylosis in patients with SpA [ 39 ] as well as with a great sensibility to non-steroidal anti-inflammatory drugs as in SpA [ 40 ]. In this model, the role of Mycobacteria alone in the intestinal changes is questionable.…”

Section: Discussionmentioning

confidence: 99%

Increased gut permeability and intestinal inflammation precede arthritis onset in the adjuvant-induced model of arthritis

Hecquet,

Totoson,

Martin

et al. 2023

Arthritis Res Ther

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Background Intestinal inflammation, dysbiosis, intestinal permeability (IP), and bacterial translocation (BT) have been identified in patients with spondyloarthritis but the time at which they appear and their contribution to the pathogenesis of the disease is still a matter of debate. Objectives To study the time-course of intestinal inflammation (I-Inf), IP, microbiota modification BT in a rat model of reactive arthritis, the adjuvant-induced arthritis model (AIA). Methods Analysis was performed at 3 phases of arthritis in control and AIA rats: preclinical phase (day 4), onset phase (day 11), and acute phase (day 28). IP was assessed by measuring levels of zonulin and ileal mRNA expression of zonulin. I-inf was assessed by lymphocyte count from rat ileum and by measuring ileal mRNA expression of proinflammatory cytokines. The integrity of the intestinal barrier was evaluated by levels of iFABP. BT and gut microbiota were assessed by LPS, soluble CD14 levels, and 16S RNA sequencing in mesenteric lymph node and by 16S rRNA sequencing in stool, respectively. Results Plasma zonulin levels increased at the preclinical and onset phase in the AIA group. Plasma levels of iFABP were increased in AIA rats at all stages of the arthritis course. The preclinical phase was characterized by a transient dysbiosis and increased mRNA ileal expression of IL-8, IL-33, and IL-17. At the onset phase, TNF-α, IL-23p19, and IL-8 mRNA expression were increased. No changes in cytokines mRNA expression were observed at the acute phase. Increased CD4+ and CD8+ T cell number was measured in the AIA ileum at day 4 and day 11. No increase in BT was observed. Conclusion These data show that intestinal changes precede the development of arthritis but argue against a strict “correlative” model in which arthritis and gut changes are inseparable.

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“…Diverse anti-RA drugs are available in the market, which includes but is not limited to NSAIDs, selective COX-2 inhibitors, and disease-modifying anti-rheumatic drugs. Both NSAIDs and corticosteroids are commonly used as adjuvants, because they relieve pain and inflammation in RA (Verhoeven et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Safety evaluation of a proprietary ayruveda-based polyherbal preparation (arthralgex) used for arthritis

Ukkinadka,

Badanthadka

2024

Braz. J. Biol.

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Arthralgex is a proprietary polyherbal preparation used in clinics to treat rheumatoid arthritis for decades. Its safety evaluation has not been reported. The study is aimed at evaluating the safety of arthralgex using Wistar rats, as per OECD guidelines. According to OECD 407, rats of either gender were separated into six groups (n= 6 each). The dose of arthralgex was decided based on an acute toxicity study. Under the treatment group, separate set of rats received arthralgex in three dose levels like - low, medium, and high (200, 400 & 800 mg/kg/day; p.o for 28 days). Satellite groups received high dose (800 mg/kg/day, p.o for 28 days), and control group received equal volume of vehicle. On day 28, blood samples were collected to estimate hematology and biochemistry parameters. Subsequently, rats were euthanized to collect organs for weighing and histopathology. Satellite groups were maintained for an additional 14 days post-treatment to assess toxicity reversibility and euthanized on day 43. Arthralgex did not show any signs of toxicity or major change in body weight in the acute toxicity study. Arthralgex has no significant adverse effect on general health status as confirmed by body weight, feed intake, hematology, biochemistry, urine analysis, internal organs, relative organ weight, and histopathological evaluation after 28 day treatment. Arthralgex could be considered safe for short-term treatment. Present findings may help researchers in dose fixing for sub-chronic and chronic toxicity studies, which is essential for safety evaluation for long-term use.

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Structural efficacy of NSAIDs, COX-2 inhibitor and glucocorticoid compared with TNFα blocker: a study in adjuvant-induced arthritis rats

Cited by 6 publications

References 18 publications

The effect of uricase on monosodium urate (MSU) crystallization, IL-1β and TNFα in monosodium urate-induced arthritis

The effect of uricase on monosodium urate (MSU) crystallization, IL-1β and TNFα in monosodium urate-induced arthritis

Increased gut permeability and intestinal inflammation precede arthritis onset in the adjuvant-induced model of arthritis

Safety evaluation of a proprietary ayruveda-based polyherbal preparation (arthralgex) used for arthritis

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