Deneysel artrit modelinde irbesartan, karvedilol ve kombine tedavinin etkisi
Yükleniyor...
Dosyalar
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Çalışmamızda irbesartan ve karvedilolün sıçanlarda deneysel olarak oluşturulan adjuvant artrit modeli üzerindeki etkisi incelendi. Toplam 6 grup oluşturuldu. Birinci grup kontrol grubu olarak ayrıldı ve 6 hayvan kullanıldı. İkinci grup salin grubu olarak ayrıldı ve 8hayvan kullanıldı. Diğer gruplar ise tedavi grubu olarak ayrıldı ve her bir grupta 9 hayvan kullanıldı. Kontrol grubu dışındaki diğer grupların sağ arka pençelerine 0.1 ml tek doz intradermal Freund’s Complete Adjuvant verilerek artrit oluşturuldu. 17-27. günler arası; 2. gruba salin (1ml/kg), üçüncü gruba irbesartan (50 mg/kg), dördüncü gruba karvedilol (1mg/kg), beşinci gruba irbesartan + karvedilol (50 mg/kg ve 1 mg/kg) uygulandı. Altıncı gruba (pozitif kontrol) diklofenak sodyum (1 mg/kg) verildi. İkinci ve altıncı gruba ilaçlar intraperitoneal, diğer gruplara ise gavaj yolu ile uygulandı. 0, 17, 20, 23 ve 27. günlerde pençe hacimleri pletismometre cihazı ile ve ağrı düzeyleri ise basıç uygulama cihazıyla ölçüldü. 27. günde intrakardiyak olarak kanlar alındı ve patolojik inceleme için arka ayak eklemleri çıkarıldı. Serumda malondialdehit, interlökin-1beta, interlökin-2, interlökin-6, interlökin-10 ve tümör nekrozis faktör- alfa düzeyleri ölçüldü ve eklemler histopatolojik olarak incelendi. Freund’s Complete Adjuvant uygulamasından sonraki 17. günde uygulanmaya başlayan ilaç tedavilerinin etkisini incelemek amacıyla 20. günde pletismometre ile sağ arka pençelerin ölçümünde, 17 ve 20. günler arasında grup 3 (irbesartan) ve grup 4 (karvedilol)’ de pençe hacimlerinin 17. gündeki değerlere göre anlamlı derecede azaldığı (p<0.05) saptanmıştır. 17 ile 23. gün karşılaştırıldığında 4. grup (karvedilol), 5. grup (kombine) ve 6. grupta (diklofenak sodyum) uygulanan tedavilerin istatistiksel olarak anlamlı (p<0.05) düzeyde pençe hacmindeki iflamasyonu ve ödemi azattığı saptanmıştır. 17 ile 27. gün karşılaştırıldığında, 20. gündeki gibi grup 3 (irbesartan) ve grup 4 (karvedilol) uygulanan gruplardaki pençe hacminde istatistiksel olarak anlamlı (p<0.05) azalma olduğu bulunmuştur. 17. günde grup 1 (kontrol) ile artrit oluşturulan gruplar (grup 2, 3, 4, 5 ve 6) karşılaştırıldığında basınç uygulama ölçüm değerleri arasında istatistiksel olarak anlamlı bir fark (p<0.05) olduğu saptandı.17 ile 20. gün basınç uygulama ölçüdeğerleri karşılaştırıldığında sadece diklofenak sodyum uygulanan 6. grupta istatistiksel anlamlılık vardı (p<0.05). 17 ile 23. gün basınç uygulama ölçüm değerleri karşılaştırıldığında; 5. grup (kombine tedavi) ve 6. grup (diklofenak sodyum)’da istatistiksel olarak anlamlılık bulundu (p<0.05). 17 ile 27. gün değerleri karşılaştırıldığında ise karvedilol (grup 4), kombine (grup 5) ve diklofenak sodyum (grup 6) alan gruplarda istatistiksel olarak anlamlı bir fark (p<0.05) saptandı. Bu sonuç karvediol ve kombine tedavinin ağrı düzeylerine etki ederek analjezik aktiviteye sahip olduklarını göstermiştir. İrbesartan ve karvedilolün uygulanan dozlarında adjuvant artrit üzerinde irbesartan tedavisinin daha çok antiinflamatuvar etki göstererek pençe hacmi değerlerini azalttığı; adjuvant artritin histopatolojik bulgularından olan vasküler proliferasyon, sinovyal proliferasyon, ödem ve inflamasyon bulgularında da kombine tedavinin daha etkili olduğu bulunmuştur. İrbesartan, karvedilol ve kombine tedavi alan gruplarda antioksidan aktivite görülmemiştir.
Abstract
In our study, the effect of the irbesartan and carvedilol on the adjuvant arthritis model formed experimentally in rats has been examined. Totally 6 groups have been formed. The first group has been separated as the control group and 6 animals have been used. The second group has been separated as the saline group and 8 animals have been used. The other groups have been separated as the treatment group and in each group, 9 animals have been used. To the back right claws of the groups other than the control group, 0.1 ml single dose intradermal Freund’s Complete Adjuvant has been given and the arthritis has been formed. Between the17-27. days; the saline has been applied to the 2nd group, irbesartan (50 mg/kg) to the third group and carvedilol to the fourth group (1 mg/kg), irbesartan + carvedilol (50 mg/kg and 1 mg/kg) to the fifth group. To the sixth group (positive control), the diclofenac sodium (1 mg/kg) has been given in its dose. To the second and sixth groups, the medicines have been applied as intravenous and via the gavage way to the other groups. On the 0, 17, 20, 23 and 27th days, pletismometer device and the pain levels have been measured with the pressure application measurement device. On the 27th days, the bloods have been taken as intracardiac and for the pathological examination, the back foot joints have been taken out. In the serum, the malondialdehit, interleukin-1beta, interleukin-2, interleukin-6, interleukin-10 and tumor necrozis factor- alfa levels have been measured and the joints have been examined as histopathologically.In order to examine effect of medical treatment that is started to be applied on the 17th day after Freund’s Complete Adjuvant application, it is detected in the measurement of right rear paw with plethysmom eter on the 20th day that paw volume in group 3 (irbesartane) and group 4 (carvedilol) has been significantly decreased (p<0.05) between 17th and 20th days according to the values in 17th day. When 17th and 23rd days are compared, it is detected that treatments applied in 4th group (carvedilol), 5th group (combined) and 6th group (diclofenac sodium) has statistically reduced the inflammation and edema in the paw volume at a significant level (p<0.05). When 17th and 27th days are compared, it is found that there is a statistically significant (p<0.05) decrease in the paw volume of groups to which group 3 (irbesartane) and group 4 (carvedilol) are applied as in the 20th day. When group 1 (control) and groups that generate arthritis (group 2, 3, 4, 5 and 6) are compared on the 17th day, it is detected that there is a statistically significant difference (p<0.05) between pressure application measurement values. When pressure application measurement values of 17th and 20th days are compared, statistical significance is only detected in the 6th group to which diclofenac sodium is applied (p<0.05). When pressure application measurement values of 17th and 23rd days are compared, statistical significance is found in 5th group (combined treatment) and 6th group (diclofenac sodium) (p<0.05). When values of 17th and 27th days are compared, a statistically significant difference (p<0.05) has been detected in carvedilol (group 4), combined (group 5) and diclofenac sodium groups (group 6). This result has shown that carvedilol and combined treatment has analgesic activity by effecting pain levels. It has been found that the irbesartan and the combined treatment has mostly shown anti-inflammatory effect on the adjuvant arthritis at the applied doses of the irbesartan and carvedilol and decreased the claw values and the vascular proliferation, synovial proliferation which are of the histopathological findings of the adjuvant arthr itis and the combined treatment have been more effective in the edema and inflammation findings. Antioxidant activity is not found in the groups receiving irbesartan, carvedilol and combined treatment
Abstract
In our study, the effect of the irbesartan and carvedilol on the adjuvant arthritis model formed experimentally in rats has been examined. Totally 6 groups have been formed. The first group has been separated as the control group and 6 animals have been used. The second group has been separated as the saline group and 8 animals have been used. The other groups have been separated as the treatment group and in each group, 9 animals have been used. To the back right claws of the groups other than the control group, 0.1 ml single dose intradermal Freund’s Complete Adjuvant has been given and the arthritis has been formed. Between the17-27. days; the saline has been applied to the 2nd group, irbesartan (50 mg/kg) to the third group and carvedilol to the fourth group (1 mg/kg), irbesartan + carvedilol (50 mg/kg and 1 mg/kg) to the fifth group. To the sixth group (positive control), the diclofenac sodium (1 mg/kg) has been given in its dose. To the second and sixth groups, the medicines have been applied as intravenous and via the gavage way to the other groups. On the 0, 17, 20, 23 and 27th days, pletismometer device and the pain levels have been measured with the pressure application measurement device. On the 27th days, the bloods have been taken as intracardiac and for the pathological examination, the back foot joints have been taken out. In the serum, the malondialdehit, interleukin-1beta, interleukin-2, interleukin-6, interleukin-10 and tumor necrozis factor- alfa levels have been measured and the joints have been examined as histopathologically.In order to examine effect of medical treatment that is started to be applied on the 17th day after Freund’s Complete Adjuvant application, it is detected in the measurement of right rear paw with plethysmom eter on the 20th day that paw volume in group 3 (irbesartane) and group 4 (carvedilol) has been significantly decreased (p<0.05) between 17th and 20th days according to the values in 17th day. When 17th and 23rd days are compared, it is detected that treatments applied in 4th group (carvedilol), 5th group (combined) and 6th group (diclofenac sodium) has statistically reduced the inflammation and edema in the paw volume at a significant level (p<0.05). When 17th and 27th days are compared, it is found that there is a statistically significant (p<0.05) decrease in the paw volume of groups to which group 3 (irbesartane) and group 4 (carvedilol) are applied as in the 20th day. When group 1 (control) and groups that generate arthritis (group 2, 3, 4, 5 and 6) are compared on the 17th day, it is detected that there is a statistically significant difference (p<0.05) between pressure application measurement values. When pressure application measurement values of 17th and 20th days are compared, statistical significance is only detected in the 6th group to which diclofenac sodium is applied (p<0.05). When pressure application measurement values of 17th and 23rd days are compared, statistical significance is found in 5th group (combined treatment) and 6th group (diclofenac sodium) (p<0.05). When values of 17th and 27th days are compared, a statistically significant difference (p<0.05) has been detected in carvedilol (group 4), combined (group 5) and diclofenac sodium groups (group 6). This result has shown that carvedilol and combined treatment has analgesic activity by effecting pain levels. It has been found that the irbesartan and the combined treatment has mostly shown anti-inflammatory effect on the adjuvant arthritis at the applied doses of the irbesartan and carvedilol and decreased the claw values and the vascular proliferation, synovial proliferation which are of the histopathological findings of the adjuvant arthr itis and the combined treatment have been more effective in the edema and inflammation findings. Antioxidant activity is not found in the groups receiving irbesartan, carvedilol and combined treatment
Açıklama
Yüksek Lisans Tezi
Anahtar Kelimeler
Karvedilol, Romatoid Artrit, Adjuvant Artrit, Diklofenak Sodyum, İrbesartan, Oksidatif Stres, İrbesartan, Rheumatoid Arthritis, Plethysmometer, Adjuvant Arthritis, Carvedilol, Diclofenak Sodium
