Etanercept improved anemia and decreased hepcidin gene expression in a rat model of rheumatoid arthritis.
Anemia of chronic disease is considered the most common extra-articular manifestation of rheumatoid arthritis (RA). The present study aimed to investigate the effect of etanercept (anti-tumor necrosis factor) on anemia and hepcidin gene expression in a rat model of RA.
Rheumatoid arthritis was induced in rats by Freund Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil, subcutaneously) on days (0, 30 and 40). Etanercept was administered subcutaneously at a dose of (0.3 mg/kg 3 times/week). Arthritis parameters, erythrocytic indices, iron profile, serum TNF-α, serum IL-6 and hepatic RT-PCR hepcidin expression were assessed.
FCA-rats developed arthritis and anemia, with significant increase of serum TNFα and IL-6 levels, and of hepcidin gene expression. In RA-rats, etanercept administration improved arthritis, corrected the erythrocyte indices and restored serum iron and ferritin with significant reduction in TNF-α, IL-6 and hepcidin gene expression. Hepcidin expression was negatively correlated to erythrocytic indices and iron profile, while it was positively correlated to serum TNF-α and IL-6 levels.
Etanercept improved anemia in this animal model of RA, which could be explained in part by the reduction in hepcidin gene expression.
Elsheemy MS
，Hasanin AH
，Mansour A
，Mehrez SI
，Abdel-Bary M
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Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.
Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05).
Pal R
，Chaudhary MJ
，Tiwari PC
，Babu S
，Pant KK
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Ephedra gerardiana aqueous ethanolic extract and fractions attenuate Freund Complete Adjuvant induced arthritis in Sprague Dawley rats by downregulating PGE2, COX2, IL-1β, IL-6, TNF-α, NF-kB and upregulating IL-4 and IL-10.
The whole plant, roots and stems of Ephedra gerardiana (Family Ephedraceae) have long been used as a folk remedy to treat rheumatism and painful joints in Northern Areas of Pakistan.
The purpose of study was to observe the preventive efficacy of Ephedra gerardiana (EG) aerial parts in treating rheumatoid arthritis using Freund's complete adjuvant (FCA) induced arthritis in rat model and to determine its possible mechanism of action.
Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. EG aqueous ethanolic extract (30:70) and its aqueous, n-butanol and ethyl acetate fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) while, PGE2 and TNF-α levels in serum samples were measured by Enzyme linked immunosorbent assay (ELISA). Moreover, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. In addition, anti-oxidant activity of plant extract and fractions was also evaluated using DPPH and reducing power assays. Also, preliminary phytochemistry and total phenolic and flavonoid contents were investigated in most active fraction (aqueous fraction).
EG extract and fractions (notably aqueous fraction) significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, the overproduction of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α were remarkably attenuated in all EG treated rats, however, IL-4 and 10 were markedly increased. The radiographic and histopathologic improvement in joint architecture was also observed in EG treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols, tannins, saponins and glycosides.
These results indicate that EG extract and fractions significantly attenuated adjuvant arthritis in rats by decreasing the levels of aforementioned pro-inflammatory and increasing the levels of anti-inflammatory mediators. This suggests that Ephedra gerardiana aerial parts might be used as a therapeutic agent for treating human arthritis.
Uttra AM
，Alamgeer
，Shahzad M
，Shabbir A
，Jahan S
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