Sinan SOYLU1, Atilla KURT2, Hakkı COŞKUN4, Musa SERİN4, Hüsnü Çağrı GENÇ4, Zeynep Deniz ŞAHİN İNAN3

Rat, akut peritonit modelinde klinik semptomlar ve hastalığın tedavisine oral strontium ranilat uygulamalarının etkilerinin araştırılması

Amaç: Cerrahi ve yoğun bakım tedavilerinde ki gelişmelere rağmen sepsis ve sistemik inflamatuar cevap sendromu(SIRS) yetişkin yoğun bakım ünitelerinde ensık ölüm sebeplerindendir. Bu sebeple peritonit ve sepsis için deney hayvanı modelinde stronsiyum ranilat'ın iyileşme üzerine etkisini biyokimyasal ve histopatolojik olarak ortaya koymayı amaçladık. Yöntem: Wistar-Albino cinsi 40 adet dişi sıçan kullanıldı. Sıçanlar; kontrol, sham[çekum ligasyon perforasyon(ÇLP)], ÇLP + Stronsiyum(S) ve S + ÇLP + S olmak üzere 4 gruba ayrıldı. Sıçanlar 7. günde ötanazi uygulandı. Peritoneal inflamasyon evrelemesi yapıldı. Patoloji için ileum rezeksiyonu yapıldı, biokimyasal inceleme için kan örnekleri alınarak IL-1, IL-6, IL- 10 ve TNF-alpha, bakıldı. Bulgular: Peritoneal inflamasyon skoru en düşük kontrol grubunda, en yüksek CLP grubunda bulundu. ÇLP+S grubunda ÇLP grubuna göre iyileşme, S+ÇLP+S grubunda ise ÇLP+S grubuna göre daha fazla iyileşme vardı. Histopatolojik değerlendirmeye göre de incebarsak hasarı en düşük kontrol grubunda, en yüksek ÇLP grubunda bulundu. ÇLP+S grubunda ÇLP grubuna göre daha hafif hasar, S+ÇLP+S grubunda ise ÇLP+S grubuna göre daha hafif hasar vardı. TNF?, IL-1, IL-6 ve Il-10 değerleri karşılaştırıldığında fark yoktu. Sonuç: Stronsiyum ranilat sepsis riski olan ve sepsis gelişmiş hastalarda proflaktik tedavi ile mortalite ve morbiditeyi azaltabilir.

Clinical symptoms of rat acute peritonitis model and study over effects of oral strontium ranelate administration for the treatment

Objective: Despite the improvements in the treatments of surgical and intensive care, sepsis and systemic inflammatory response syndrome are the most common cause of mortality. Therefore in the experimental animal model, we aimed to reveal biochemical and histopathologic effects of strontium ranelate on healing in experimental animal model for peritonitis and sepsis. Method: 20 female Wistar-Albino rats were used.Rats were seperated into 4 groups; control, sham [ceacum ligation perforation (CLP)], CLP + Strontium (S) (CLP+S) and S+CLP+S. Rats were euthanised on 7th day. Peritoneal inflammation staging and ileum resection was performed. Blood samples were taken for biochemical screening and IL1, IL-6, IL-10 and TNF-alpha tests were evaluated. Results: Peritoneal inflammation score was the highest at CLP group and the lowest at control group. There was healing in CLP+S group compared to CLP group, and more healing in S+CLP+S group compared to CLP+S group. According to histopathological evaluation, ileum injury was the lowest in the control group and the highest in CLP group. Less injury was found in CLP+S group compared to CLP group, and less injury was found in S+CLP+S group compared to CLP+S group. No difference was found when TNF-alpha, IL-1, IL-6 and IL-10 values were compared. Conclusions: Strontium ranelate may reduce mortality and morbidity by prophylactic treatment in patients at risk of sepsis and patients with sepsis.

PDF

___

1- Pieracci, F.M., Barie, P.S.Intra-abdominal infections. Curr. Opin. Crit. Care 2007;13, 440-9.
2- Topal F, Yonem O, Tuzcu N, et al. Strontium chloride: canit be a new treatment option for ulcerative colitis? Biomed Res Int 2014: 530687. doi:10.1155/2014/530687.
3- Collaert B. and Fischer C. "Dentine hypersensitivity: a review," Endodontics & Dental Traumatology 1991; 7: 145-52.
4- Autio HKA, Scher I, and Morris MJ. "Therapeutic strategies for bone metastases and their clinical sequelae in prostate cancer," Current Treatment Options in Oncology 2012;13: 174-88.
5- Huang C, Li L, Yu X. et al. The inhibitory effect of strontiumdoped calcium polyphosphate particles on cytokines from macrophages and osteoblasts leading to aseptic loosening in vitro. BiomedicalMaterials 2014; 9, Article ID025010.
6- Yamaguchi M, Weitzmann MN. The intact strontium ranelate complex stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-?B activation.Molecular and Cellular Biochemistry 2012; 359: 399-07.
7- Buache E, Velard F, Bauden E et al. "Effect of strontium substituted biphasic calcium phosphate on inflammatory mediators production by humanmonocytes," Acta Biomaterialia 2012; 8: 3113-9.
8- Rittirsch D, Hoesel LM, Ward PA. The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol 2007; 81: 137-43.
9- Simon R, Wetzel W, Winsey K, et al. Supplemental dietary tyrosine in sepsis and acute hemorrhagic shock. Arch Surg, 1987; 122: 78-81.
10- Chui CJ, McArdle AH, Brown R, et al. Intestinal mucosal lesion in lowflow states. A morphological, hemodynamic and metabolic reappraisal. Arch Surg 1970;101(4):478-83.
11- Parker SJ, Watkins PE. Experimental models of gram-negative sepsis. Br J Surg 2001; 88: 22-30.
12- Cavaillon JM, Annane D. Compartmentalization of the inflammatory response in sepsis and SIRS. J Endotoxin Res 2006; 12: 151-70.
13- Van der Wal JB, Jeekel J. Biology of the peritoneum in normal homeostasis and after surgical trauma. Colorectal Dis 2007; 9: 9-13.
14- Michie HR, Manogue KR, Spriggs DR, et al. Detection of circulating tumor necrosis factor after endotoxin administration. N Eng J Med 1988; 318: 1481-86.
15- Chowers Y, Cahalon L, Lahav M, et al. Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha- and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells. J Immunol 2000, 15; 165: 2955-61.
16- Messer J, Eyer D, Donato L, et al. Evaluation of IL-6 and soluble receptors of TNF for early diagnosis of neonatal infection. J Pediatr 1996; 129: 574-80.
17- Panero A, Pacifico L, Rossi N, et al. IL-6 in neonates with early and late onset infection. Pediatr Infect Dis J 1997; 16: 370-5.
18- Şahin Y, Şahin DA. Yenidoğan sepsisinin erken tanısında C-reaktif protein ve interlökin-6'nın rolü. Türk Pediatri Arşivi 2004; 39: 171-7.
19- Pérez Fernández R, Kaski JC. Interleukin10 and coronary disease. Rev Esp Cardiol 2002; 55: 738-50.