KALSİYUM DOBESİLAT'IN İNTRAABDOMİNAL ADEZYON ÖNLEYİCİ ETKİSİ: DENEYSEL ÇALIŞMA

Yıl 2020, , 209 - 214, 31.12.2020

Berkay Küçük Salih Tuncal , Osman Aydın Yılmaz Ünal Yusuf Murat Bağ , Zeynep Adıyaman Mehmet Şenes , Pınar Celepli , Sema Hücümenoğlu Bülent Kılıçoğlu , Kemal Kısmet , Ertuğrul Ertaş

https://doi.org/10.20492/aeahtd.459184

Öz

ÖZET:

 

AMAÇ: Kalsiyum
Dobesilat'ın
(Ca-Dob) postoperatif intraabdominal adezyon oluşumunu önlemedeki etkinliğini
deneysel çekal abrazyon modelinde göstermeyi amaçladık.

 

GEREÇ VE YÖNTEMLER: Çalışmada kullanılan 30 adet Wistar Albino
dişi rat  randomize olarak 3 gruba
ayrıldı. Sham grubuna laparotomi yapıldı, çekum batın dışına alındıktan sonra
herhangi bir işlem yapılmadan batına konuldu. Kontrol grubuna çekal abrazyon ve
periton rezeksiyonu sonrası herhangi bir işlem yapılmadı. Ca-Dob grubuna çekal abrazyon ve periton rezeksiyonu yapıldıktan
sonra batın kapatıldı, sadece bu gruba 21 gün boyunca 100 mg/kg/gün dozunda
orogastrik yolla Ca-Dob verildi. Tüm ratlar
postoperatif 21. gün sakrifiye edildi. Adezyon değerlendirmesi yapıldı. Periton
ve barsaktan alınan doku örnekleri inflamasyon ve fibrozis derecelerini
belirlemek için histopatolojik incelemeye gönderildi. Ayrıca, biyokimyasal
analiz için doku ve kan örnekleri alındı.

 

BULGULAR: Ca-Dob uygulanan sıçanlarda
inflamasyon, makroskopik adezyon ve fibrozis skorlarının kontrol grubuna göre
istatistiksel olarak anlamlı derecede düşük olduğu saptandı (p<0,05).Yine, Ca- Dob grubunda doku MDA, doku FOÜ
ve doku TOS değerlerinin  kontrol grubuna
göre istatistiksel olarak anlamlı derecede düşük olduğu görüldü (p=0,001).
Ayrıca sham grubundaki  doku total SH
değerlerinin, kontrol grubuna göre istatistiksel olarak anlamlı derecede yüksek
olduğu saptandı (p<0,05). Son olarak; Ca- Dob grubunda serum MDA ve  serum TOS değerlerinin,  kontrol grubuna göre istatistiksel olarak
anlamlı derecede düşük olduğu görüldü (p<0,05).

 

SONUÇ: Ca-Dob’ın
çekal abrazyon modelinde adezyon oluşumunu engellemede etkin olduğunu tespit
ettik. Histopatolojik olarak gösterilen antiinflamatuvar etkinin yanı sıra,
biyokimyasal olarak saptanan antioksidan etkinin, Ca-Dob’ın adezyon önleyici etkinliğinde rol oynadığı sonucuna
varılmıştır.

Anahtar Kelimeler

Kalsiyum Dobesilat, Antiinflamatuar, Antioksidan, Adezyon, Deneysel

THE EFFECT OF CALCIUM DOBESILATE ON THE PREVENTION OF EXPERIMENTAL INTRA-ABDOMINAL ADHESIONS

Öz

ABSTRACT:

 

OBJECTIVE: It was aimed to demonstrate the efficacy
of Calcium Dobesilate (Ca-Dob) in preventing postoperative intra-abdominal
adhesion formation in an experimental cecal abrasion model.

 

MATERIALS AND METHODS: Thirty female
Wistar Albino rats were randomized into 3 groups. In the sham group, the cecum
was removed from the abdomen and replaced without any further processing. In
the control group, after cecal abrasion and peritoneal resection no processing
was applied. In the Ca-Dob group, after cecal abrasion and peritoneal resection,
100 mg/kg/day Ca-Dob was administered. All rats were sacrificed on 21st day.
The evaluation of adhesions was made through the degrees of bowel inflammation
and fibrosis in tissue samples and the biochemical analysis of tissue and blood
samples.

 

RESULTS: Statistically, inflammation, microscopic adhesions and fibrosis scores
were found to be significantly lower in the Ca-Dob administered rats compared to the control group (p
< 0.05). Tissue MDA, FOP and TOS values were found to be significantly lower
statistically compared to the control group (p = 0.001). Tissue total SH values
were found to be statistically significantly higher (p < 0.05) in the sham
group compared with the control group. Finally; serum MDA and serum TOS values in
the Ca-Dob group, was statistically significantly lower (p < 0.05) compared
to control group.

 

CONCLUSION: Ca-Dob was found to be efficacious in preventing the
formation of adhesions. In addition to the demonstrated anti-inflammatory effect
histopathologically, the effect of antioxidant effect demonstrated
biochemically was concluded to participate to the adhesion preventive efficacy
of Ca-Dob.

Anahtar Kelimeler

Calcium Dobesilate, Anti-inflammatory, Antioxidant, Adhesion, Experimental

Kaynakça

• References
• [1] Attard JA, MacLean AR. Adhesive small bowel obstruction: epidemiology, biology and prevention. Can J Surg. 2007;50:291-300.[2] Saba D, Yavuz H, Senkaya I, et al. The effects of calcium dobesilate on skeletal muscle ischemia reperfusion injury. Turkish J Thor Card Vasc Surg. 2000;8:797 801.[3] Angehm F. Swiss study group. Efficacy and safety of calcium dobesilate in patients with chronic venous insufficiency. Curr Ther Res. 1995;56:346-357.[4] Ruiz E, Lorente R, Tejerina T. Effects of calcium on dobesilate on the synthesis of endothelium-dependent relaxing factors in rabbit isolated aorta. Br J Pharmacol.1997;121:711-716.[5] Suschek C, Kolb H, Kolb-Bachofen V. Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells. Br J Pharmacol.1997;122:1502-1508.[6] Hooker GD, Taylor BM, Driman DK. Prevention of adhesion formation with use of sodium hyaluronate based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh: A randomized controlled study. Surgery. 1999;25:211-216.[7] Celeplı S, Kismet K, Kaptanoğlu B, et al. The effect of oral honey and pollen on postoperative intraabdominal adhesions. Turk J Gastroenterol. 2011;22:65-72.[8] Karimi M, Yazdan AS, Parsaei P, et al. The effect of ethanol extract of rose (Rosa damascena) on intra-abdominal adhesions after laparotomy in rats. Wounds. 2016;28:167-174.[9] Wu T, Rifai N, Roberts LJ 2nd, et al. Stability of measurements of biomarkers of oxidative stress in blood over 36 hours. Cancer Epidemiol Biomarkers Prev. 2004;13:1399-1402.[10] Ohkawa H, Ohishi N, Yagi K. Assay for lipidperoxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-358[11] Verde V, Fogliano V, Ritieni A, et al. Use of N,N-dimethyl-p-phenylenediamine to evaluate the oxidative status of human plasma. Free Radic Res. 2002;36: 869-873.[12] Holmdahl L, Ericsson E, Ericsson BI, et al. Depression of peritoneal fibrinolysis during operation is a local response to trauma Surgery. 1998;123:539-544.[13] Van Der Krabben AA, Dijkstra FR, Nieuwenhuijzen M, et al. Morbidity and mortality of inadvertent enterotomy during adhesiotomy. Brit J Surg. 2000;87:467-471.[14] Ergul E, Korukluoglu B. Peritoneal adhesions: facing the enemy. Int J Surg. 2008;6:253-260.[15] Practice Committee of the American Society for Reproductive Medicine. Control and Prevention of Peritoneal Adhesions in Gynecologic Surgery. Fertil Steril. 2006;86(5 Suppl 1):S1-5.[16] González-Quintero VH, Cruz-Pachano FE. Preventing adhesions in obstetric and gynecologic surgical procedures. Rev Obstet Gynecol. 2009;2:38-45.[17] Maciver AH, McCall M, James Shapiro AM. Intra-abdominal adhesions: cellular mechanisms and strategies for prevention. Int J Surg. 2011;9:589-594.[18] Arung W, Meurisse M, Detry O. Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol. 2011;17:4545-4553.[19] Ten Raa S, van den Tol MP, Sluiter W, et al. The role of neutrophils and oxygen free radicals in post-operative adhesions. J Surg Res. 2006;136:45-52.[20] Ten Broek RP, Stommel MW, Strik C, et al. Benefits and harms of adhesion barriers for abdominal surgery: a systematic review and meta-analysis. Lancet. 2014;383:48-59.[21] Montz FJ, Monk BJ, Lacy SM, et al. Ketorolac tromethamine, a nonsteroidal antiinflammatory drug: ability to inhibit post-radical pelvic surgery adhesions in a porcine model. Gynecol Oncol. 1993;48:76-79.[22] Steinleitner A, Lambert H, Kazensky C, et al. Pentoxifylline, a methylxanthine derivative, makes postsurgical adhesion reformation in rabbits. Obstet Gynecol.1990;75:926-928.[23] Hellebrekers BW, Trimbos-Kemper TC, Trimbos JB, et al. Use of fibrinolytic agents in the prevention of postoperative adhesion formation. Fertil Steril. 2000;74:203-212.[24] Cerrahoglu M, Taner KA, Iskesen I, et al. Calcium dobesilate reduces oxidative stress in cardiac surgery. J Cardiovasc Surg. 2009;50:695-701.[25] Tejerina T, Ruiz E. Calcium Dobesilate: pharmacology and future approaches. Gen Pharmacol. 1998;31:357-360.[26] Brunet J, Farine JC, Garay RP, et al. Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat. Eur J Pharmacol. 1998;358:213-220.[27] Seker A, Bardakci O, Eryilmaz S, et al. Does calcium dobesilate protect against intestinal ischemia-reperfusion injury induced in rats? Eur Rev Med Pharmacol Sci. 2016;20:2168-2173.[28] Garay RP, Hannaert P, Chiavaroli C. Calcium dobesilate in the treatment of diabetic retinopathy. Treat Endocrinol. 2005;4:221-232.