AB0136 Can Nitric Oxide (NO) Regulator Drugs be Used as Treatment for Muscle Loss in Collagen-Induced Arthritis (CIA)?
Authors: P.V.G. Alabarse, V.D.O.N. Teixeira, J.M.D.S. Silva, A.S. Almeida, L.I. Filippin, R.M. Xavier
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis is an autoimmune disease of unknown etiology associated with progressive disability, systemic complications like fatigue and muscle weakness, early death, and socioeconomic costs [1,2]. Nitric oxide (NO) have been related with inflammation and its regulation can lead to anti-inflammatory and anti-arthritic effects in CIA as well as induce muscle repair in muscle injury [3,4]. The role of NO in CIA muscle loss has not yet been studied. <h3>Objectives</h3> How NO synthase inhibitor (NG-nitroL-arginie methy ester: L-NAME) and the NO donor (3-morpholinosydnonimine: SIN-1) affects CIA muscle loss? <h3>Methods</h3> Female Wistar rats with CIA [5] were separated in four groups: CIA (saline, n=10); L-NAME (30mg kg<sup>-1</sup> n=10); and SIN-1 (0.3 mg kg<sup>-1</sup>, n=13), treated twice a day for 10 days after the onset of the disease, and a wildtype group (WT, n=8). Clinical score (arbitrary units – au), hind paw edema (mm), spontaneous locomotion (cm), and body weight (g) were analyzed. Ankle was collected and used for histological confirmation of the disease. Tibialis anterior (TA), gastrocnemious and soleus muscles were weighted (g). TA was used for histological analysis and immune stained for TNF-alfa, TGF-beta and IL-1beta. Serum was collected for albumin (g dL<sup>-1</sup>), total iron (μg dL<sup>-1</sup>) and ionized calcium (mg dL<sup>-1</sup>) analysis. Proper statistics were performed and p&lt;.05 was set for critical limit. Data are in Mean ± SEM. <h3>Results</h3> Ankle histology confirmed that all CIA groups developed arthritis. In vivo analysis of hindpaw edema, clinical score, body and muscle weight, and spontaneous locomotion showed no difference among CIA groups. On the other hand, both L-NAME (48±6,5) and SIN-1 (48±6,5) groups have shown statistically decreased clinical score than saline (77±9,2) when analyzed by the area under curve. Muscle cross sectional area were higher in L-NAME (1074±315 μm) and SIN-1 (1115±303 μm) than saline (786±243 μm), however it did not reach WT diameter (1755±278 μm). Blood vessels diameter were smaller in L-NAME (287±121 μm) group compared to SIN-1 (524±169 μm) and saline (445±165 μm). Albumin was lower in all CIA groups (saline 3,8±0,2; L-NAME 3,9±0,1; SIN-1 3,7±0,1; WT 4,2±0,1), and ionized calcium had no difference among all groups. Iron was decreased in L-NAME (229±42) and SIN-1 (226±62) than WT (353±53). All CIA groups had shown increased immune cells infiltration shown by TNF-alfa, TGF-beta and IL-1beta immune staining. <h3>Conclusions</h3> The data above mentioned suggests that nitric oxide regulator drugs show good prospects as intervention for muscle loss. As was observed, even a simply drug that have main influence in vessel pressure shows preventive clinical score development and ameliorates muscle cross sectional area. The mechanism behind such findings will soon be depicted by molecular analysis. <h3>References</h3> McInnes IB, Schett G. NEJM 2011;365(23):2205-19. Alver A, et al. Clinical Biochemistry 2011;44(17-18):1385-9. Gomaa A, et al. BJP 2009;158(7):1835-47. Filippin LI, et al. Nitric Oxide 2009;21(3-4):157-63. Rosloniec EF, et al. Curr Protoc Immunol 2010; Chapter 15: Unit 15.5.1-25. <h3>Acknowledgements</h3> Financial support: CAPES, CNPq, FAPERGS, FIPE-HCPA. <h3>Disclosure of Interest</h3> None declared