Şevki KABAK, Mehmet HALICI, Birkan YAKAN, Recep KUTLUBAY, Mustafa KULA

Tuberküloz artritini engellemede NG-monometil-L-arginin ve indometazinin birlikte veya tek tek kullanımdaki etkinliği

Amaç: Sıçan tüberküloz artrit modelinde nitrik oksit sentaz inhibitörü NG-monometiI-L-arginin (NMMA) ve indometazinin iyileştirici etkileri değerlendirildi. Çalışma planı: Seksen erkek Wistar sıçan 16'lık beş gruba ayrıldı. Birinci gruptaki (kontrol grubu) sıçanların sağ dizlerine %0.9 serum fizyolojik intraartiküler olarak uygulandı. Diğer gruplarda Mycobacterium tuberculosis suşlarından hazırlanan solüsyondan 0.1 ml sağ dizlere intraartiküler uygulandı ve tüberküloz artrit oluşturuldu. İkinci grupta tedavi uygulanmadı. Üçüncü gruba ağızdan indometazin verildi. Dördüncü gruba intraperitoneal olarak NMMA verildi. Beşinci grupta ise indometazin ve NMMA birlikte uygulandı. Artrit oluşturulmasından sonra 3, 7, 14 ve 21. günlerde her gruptan dörder sıçanda dizlerde artrit oluşumu değerlendirildi. Daha sonra Tc99 nanokolloid içeren solüsyon verilerek fokal aktivite tutulumları sintigrafik görüntülemeyle incelendi. Kantitatif değerlendirme ile eklem/yumuşak doku oranları hesaplandı. Daha sonra eter anestezisi ile öldürülen deneklerin diz çevresi kemiklerinde Gries reaksiyonu ile nitrit/nitrat ölçümü yapıldı. Deneklerin diz eklemleri histopatolojik incelemeye alındı. Sonuçlar: On dördüncü günde, NMMA verilen grupta artrit oluşumu bir puan azalmışken, 21. günde indometazin ve NMMA'nın birlikte verildiği grupta artrit skoru sıfır idi. Sintigrafik incelemede, 3 ve 7. günlerde artmış aktivite tutulumu gözlenirken, 21. günde NMMA ve indometazinin birlikte verildiği grupta aktivite tutulumunun olmadığı gözlendi. Histopatolojik incelemede 21. günde NMMA'nın tek başına veya indometazinle birlikte uygulandığı gruplarda kronik iltihabi hücre infiltrasyonunun ortadan kalktığı görüldü. Deney süresince 2. gruptan 4, 3. gruptan 2 sıçan sepsisten dolayı öldüler. Griess reaksiyonu ile, beşinci grupta sıçanların 21. gündeki sonuçları kontrol grubu değerlerine yakın bulundu (p>0.05). Çıkarımlar: Artritin eklem üzerindeki olumsuz etkilerini ortadan kaldırmak için indometazin ve NMMA'nın birlikte uygulanmasının daha etkili olduğu görüldü.

Anahtar Kelimeler:

Anti-enflamatuvar ajanlar, steroid olmayan, Arginin, Artrit, enfeksiyöz, İndometazin, Mycobacterium enfeksiyonları, Nitrik oksit, Radyonüklid görüntüleme, Mycobacterium tuberculosis, Nitritler, Sıçan, Wistar, Modeller, hayvan

Comparison of the effects of NG-monomethyl-L-arginine and indomethacin on tuberculous arthritis. An experimental study in rats

Objectives: We evaluated therapeutic effects of NG-monomethyl-L-arginine, a nitric-oxide synthase inhibitor, and indomethacin in a rat model of tuberculous arthritis. Methods: Eighty male Wistar albino rats were randomly divided into five equal groups. In the first group (controls) normal saline solution was injected into the right knee joints of the rats. In the remaining groups, tuberculous arthritis was induced in the right knee joints of the rats via injection of 0.1 ml of a solution prepared from Mycobacterium tuberculosis strains. No treatment was given to the second group. The third and forth groups were assigned to receive oral indomethacin and intraperitoneal NMMA, respectively, while the fifth group received a combination thereof. The occurrence of arthritis was evaluated in four rats in each group on the 3rd, 7th, 14th, and 21st days after induction of arthritis. The rats were then subjected to scintigraphic imaging with Tc99 and focal activity involvement was analysed. The ratio of joint to soft tissue was calculated quantitatively. Following sacrifice with ether anesthesia, nitrate/nitrite levels were measured via Griess reaction in the bone tissue adjoining the knee. The knee joints were histopathologically examined. Results: The severity of arthritis in the NMMA group decreased by one point on the 14th day. On Day 21, arthritis score was zero in rats receiving a combination of indomethacin and NMMA. Scintigraphic examination revealed increased uptake activity on the 3rd and 7th days, whereas no uptake activity was seen on the 21st day in the group receiving both indomethacin and NMMA. Histopathologically, chronic inflammatory infiltration disappeared on Day 21 in rats receiving either NMMA alone or in combination with indomethacin. During the experiment, four rats in the second group and two rats in the third group died from sepsis. Nitrate measurements of the fifth group on Day 21 showed approximate values to those of the control group (p>0.05). Conclusion: The combined use of indomethacin and NMMA seems to be more efficacious in reducing negative effects of tuberculous arthritis on the joint.

Keywords:

Anti-Inflammatory Agents, Non-Steroidal, Arginine, Arthritis, Infectious, Indomethacin, Mycobacterium Infections, Nitric Oxide, Radionuclide Imaging, Mycobacterium tuberculosis, Nitrites, Rats, Wistar, Models, Animal,

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