The anti-arthritic and anti-oxidative effect of NBD (6-nitro-1,3-benzodioxane) in adjuvant-induced arthritis (AIA) in rats

Shah, Syed Muhammad Hassan; Ashraf, Nadeem; Soomro, Zahid; Shah, Muhammad Raza; Kabir, Nurul; Simjee, Shabana Usman

doi:10.1007/s00011-012-0480-4

Cited by 17 publications

(9 citation statements)

References 76 publications

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“…After decalcification, the samples were processed, embedded, cut into 10 μ m sections, and stained with haematoxylin and eosin (H & E). The severity of the arthritis in knee joint was scored numerically; that is, the pathology was rated 0 to 5, with 0 being normal and 5 being the greatest extent and degree of involvement [34, 35]. …”

Section: Methodsmentioning

confidence: 99%

The Anti-Arthritic and Immune-Modulatory Effects of NHAG: A Novel Glucosamine Analogue in Adjuvant-Induced Arthritis

Shah

Jawed

Awan

et al. 2013

BioMed Research International

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Rheumatoid arthritis (RA) is potentially devastating condition which lacks good treatment options. Pro-inflammatory cytokines interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and oxidative stress markers such as nitric oxide (NO) and peroxide (PO) are mediators of RA pathogenesis. In the present study N-[2,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-3-yl]acrylamide (NHAG), analogue of glucosamine, was evaluated in adjuvant-induced arthritic model of rats. The disease progression was monitored by analysing arthritis scoring, loss of body weight, paw oedema, and histological changes in joints. RA associated hyperalgesia was evaluated by gait analysis. The serum or plasma levels of NO, PO, glutathione (GSH) superoxide dismutase (SOD) IL-1β and TNF-α were analyzed to monitor the state of disease severity. The arthritic control animals exhibited significant increase in arthritic score (P < 0.003) and paw oedema (P < 0.001) with parallel loss in body weight (P < 0.04). The NHAG-treated arthritic animals exhibited refinement in the gait changes associated with arthritis. NHAG also significantly decreased the NO (P < 0.02) and PO (P < 0.03) with concurrent increased in GSH (P < 0.04) and SOD (P < 0.007). Both IL-1β (P < 0.001) and TNF-α (P < 0.001), were significantly decreased in NHAG-treated group. Thus NHAG might have a therapeutic potential for arthritis by exerting antioxidative and immunomodulatory effects.

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Section: Methodsmentioning

confidence: 99%

The Anti-Arthritic and Immune-Modulatory Effects of NHAG: A Novel Glucosamine Analogue in Adjuvant-Induced Arthritis

Shah

Jawed

Awan

et al. 2013

BioMed Research International

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“…The adjuvant-arthritis animal model is very similar to human rheumatoid arthritis and resembles pathological and serological changes, including inflammatory mediators. 17 In the adjuvant-induced arthritis model, rat develops chronic swelling and pain in multiple joints with a release of cytokines from inflammatory cells, culminating in the erosion of cartilage and bone destruction, causing severe disability. 18 Inflammation in the CFA arthritis model is indicated by an increase in paw volume of the injected paw.…”

Section: Biological Assaysmentioning

confidence: 99%

Synthesis and evaluation of the anti-nociceptive and anti-inflammatory activity of 4-aminoquinoline derivatives

Santos

Barros

Bortoluzzi

et al. 2015

Bioorganic & Medicinal Chemistry

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In this paper, we describe the synthesis and pharmacological evaluation of a series of 4-aminoquinolines. The compounds were characterised and tested in models of pain and inflammation, using the writhing test with acetic acid, formalin test, peritonitis test by zymosan and arthritis test with Freund's adjuvant complete assay. The results revealed that all of the 4-aminoquinolines that were prepared promoted anti-nociceptive activity as well as acute and chronic anti-inflammatory effects, with marked activity in the derivates labelled with BAQ and 7-CF3-MAQ. After 7 days of treatment, 7-CF3-MAQ did not induce significant hepatotoxicity, gastrotoxicity or nephrotoxicity.

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“…AIA model shares many pathological features with RA including inflammation, synovial hyperplasia and aggressive pannus formation which lead to cartilage and bone damage [ 23 ]. AIA model is used extensively to elucidate the pathogenic mechanisms relevant to RA and to identify potential targets for therapeutic intervention [ 24 , 25 ]. Therefore, rat AIA is the suitable experimental model for the present study to investigate the possible pathological role of Hh signal in cartilage damage of RA.…”

Section: Discussionmentioning

confidence: 99%

Expression of hedgehog signal pathway in articular cartilage is associated with the severity of cartilage damage in rats with adjuvant-induced arthritis

Cai

et al. 2015

J Inflamm

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BackgroundCartilage damage is a crucial step in rheumatoid arthritis (RA) disease progress while its molecular mechanisms are not fully understood. Here we investigated the expression of hedgehog (Hh) signal pathway in articular cartilage of adjuvant-induced arthritis (AIA) rats and its possible pathological role in cartilage damage.Methods30 rats were divided into sham and AIA group (n = 15). Complete Freund’s adjuvant was used to induce AIA. Secondary paw swelling was measured on day 10, 14, 18, 22 and 26 after induction. Rats were sacrificed on day 26 and knee joints and cartilage tissues were collected. Paw swelling, cartilage histopathologic changes and OARSI scores were used to evaluate AIA in rats. The protein expression of Hh signal related genes (Shh, Ptch1, Smo and Gli1) in cartilage were assayed by immunohistochemistry. The mRNA levels of Shh, Ptch1, Smo, Gli1, type-II collagen (COII) and aggrecan in cartilage were assayed by real-time PCR. In vitro study, cultured AIA chondrocytes were treated with cyclopamine (a specific inhibitor of Hh signal) and the mRNA levels of Hh signal and ECM components (COII and aggrecan) were measured by real-time PCR.ResultsImmunohistochemical results revealed that Shh, Ptch1, Smo and Gli1 proteins showed higher expression in the articular cartilage of AIA rats than those of sham rats. Real-time PCR results confirmed that Shh, Ptch1, Smo and Gli1 mRNA levels in cartilage tissues of AIA rats were significantly increased compared with those of sham rats (1.6, 1.4, 1.6, 2.0 fold, respectively). The mRNA levels of Shh, Ptch1, Smo, and Gli1 were associated with the severity of cartilage damage (indicated by OARSI scores, COII and aggrecan mRNA levels in cartilage). In vitro, cyclopamine effectively decreased the mRNA levels of Shh, Ptch1, Smo and Gli1, and increased the mRNA levels of COII and aggrecan in AIA chondrocytes, suggesting Hh signal inhibition might directly promote ECM production.ConclusionsOur findings present certain experimental evidence that Hh signal pathway is involved in the pathogenesis of cartilage damage in RA.

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The anti-arthritic and anti-oxidative effect of NBD (6-nitro-1,3-benzodioxane) in adjuvant-induced arthritis (AIA) in rats

Abstract: Our results suggests that NBD is an anti-arthritic agent that not only reduces the severity of the disease process but also affects contributing factors of arthritic inflammation including free radicals and inflammatory cytokines production.

Cited by 17 publications

References 76 publications

The Anti-Arthritic and Immune-Modulatory Effects of NHAG: A Novel Glucosamine Analogue in Adjuvant-Induced Arthritis

The Anti-Arthritic and Immune-Modulatory Effects of NHAG: A Novel Glucosamine Analogue in Adjuvant-Induced Arthritis

Synthesis and evaluation of the anti-nociceptive and anti-inflammatory activity of 4-aminoquinoline derivatives

Expression of hedgehog signal pathway in articular cartilage is associated with the severity of cartilage damage in rats with adjuvant-induced arthritis

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