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CARNOSOL ALLEVIATES INFLAMMATION AND BACTERIAL TRANSLOCATION IN A RAT MODEL OF INTESTINAL ISCHEMIA-REPERFUSION INJURY

Year 2019, Volume: 5 Issue: 2, 105 - 118, 27.06.2019

Abstract

Intestinal ischemia-reperfusion injury (II/R) is a condition with significant morbidity and mortality. In this study, we aimed to demonstrate the protective effect of carnosol, an anti-oxidant, anti-inflammatory, anti-carcinogenic and anti-microbial agent, on pro-inflammatory cytokines, tissue angiopoietins, histopathological damage and bacterial translocation in rats subjected to II/R injury. Thirty male Sprague-Dawley rats were divided into 3 groups: control group, intestinal ischemia/reperfusion group (II/R) and carnosol group (II/R+C). Ischemia-reperfusion injury was conducted by laparotomy. All rats received 1010 colony forming units/milliliters E.coli 12 hours prior to surgery. II/R+C rats received 3 mg/kg/day carnosol per oral starting from 3 days prior to surgery. After 72 hours of post-surgical follow-up, rats were re-laparotomized for specimen collection. II/R+C group had lower serum TNF-α, IL-1β and IL-6 levels when compared with II/R group (p=0.026, 0.006 and 0.045, respectively). II/R group had significantly higher tissue injury when compared with II/R+C group (p<0.001). II/R+C group rats had significantly reduced liver, spleen and mesenteric lymph node culture growths when compared with II/R group. Angiopoietin I and II levels were similar between groups. In conclusion, carnosol is a powerful anti-inflammatory and anti-microbial agent in II/R injury model. We showed effective reduction of pro-inflammatory cytokine profile, improvement of histopathological damage, and prevention of bacterial translocation.

Supporting Institution

Financial funding was obtained from Trakya University Scientific Studies Fund.

Project Number

Financial funding was obtained from Trakya University Scientific Studies Fund.

Thanks

Financial funding was obtained from Trakya University Scientific Studies Fund.

References

  • Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am 1992; 72:65-83.
  • Sorkine P, Szold O, Halpern P, Gutman M, Greemland M, Rudick V, et al. Gut decontamination reduces bowel ischemia-induced lung injury in rats. Chest 1997; 112:491-5.
  • Schoenberg MH, Beger HG. Reperfusion injury after intestinal ischemia. Crit Care Med 1993; 21:1376-86.
  • Tullis MJ, Brown S, Gewertz BL. Hepatic influence on pulmonary neutrophil sequestration following intestinal ischemia-reperfusion. J Surg Res. 1996; 66: 143-6.
  • Börjesson A, Norlin A, Wang X, Andersson R, Folkesson HG. TNF-alpha stimulates alveolar liquid clearance during intestinal ischemia-reperfusion in rats. Am J Physiol Lung Cell Mol Physiol 2000; 278: L3-12.
  • Simpson R, Alon R, Kobzik L, Valeri CR, Shepro D, Hechtman HB. Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion. Ann Surg 1993; 218: 444-53.
  • Towfigh S, Heisler T, Rigberg DA, Hines OJ, Chu J, McFadden DW, et al. Intestinal ischemia and the gut-liver axis: an in vitro model. J Surg Res 2000; 88:160-4.
  • Turnage RH, Guice KS, Oldham KT. Endotoxemia and remote organ injury following intestinal reperfusion. J Surg Res 1994; 56: 571-8.
  • Köksoy C, Kuzu MA, Kuzu I, Ergün H, Gürhan I. Role of tumour necrosis factor in lung injury caused by intestinal ischaemia-reperfusion. Br J Surg 2001; 88:464-8.
  • Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000; 6: 460-3.
  • Kim I, Moon SO, Park SK, Chae SW, Koh GY. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res 2001; 89:477-9.
  • Pizurki L, Zhou Z, Glynos K, Roussos C, Papapetropoulos A. Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Br J Pharmacol 2003; 139:329-36.
  • Mandriota SJ, Pepper MS. Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res 1998; 83:852-9.
  • Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 2006; 12:235-9.
  • Conesa EL, Valero F, Nadal JC, Fenoy FJ, López B, Arregui B, et al. N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal failure. Am J Physiol Regul Integr Comp Physiol 2001;281: R730-7.
  • Maghsoudi S, Gol A, Dabiri S, Javadi A. Preventive effect of ginger (Zingiber officinale) pretreatment on renal ischemia-reperfusion in rats. Eur Surg Res 2011; 46:45-51.
  • Baud L, Ardaillou R. Reactive oxygen species: production and role in the kidney. Am J Physiol 1986; 251: F765-76.
  • Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970; 101:478-83.
  • Günel E, Cağlayan F, Cağlayan O, Dilsiz A, Duman S, Aktan M. Treatment of intestinal reperfusion injury using antioxidative agents. J Pediatr Surg 1998; 33:1536-9.
  • Tian XF, Yao JH, Zhang XS, Zheng SS, Guo XH, Wang LM, et al. Protective effect of carnosol on lung injury induced by intestinal ischemia/reperfusion. Surg Today 2010; 40:858-65.
  • Yao JH, Zhang XS, Zheng SS, Li YH, Wang LM, Wang ZZ, et al. Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion. World J Gastroenterol 2009; 15:3240-5.
  • Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC, et al. Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects. Biosci Biotechnol Biochem 2007; 71:2223-32.
  • Chen CC, Chen HL, Hsieh CW, Yang YL, Wung BS. Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival. Acta Pharmacol Sin 2011; 32:62-9.
  • Chae IG, Yu MH, Im NK, Jung YT, Lee J, Chun KS, et al. Effect of Rosemarinus officinalis L. on MMP-9, MCP-1 levels, and cell migration in RAW 264.7 and smooth muscle cells. J Med Food 2012; 15:879-86.
  • Yao H, Chen Y, Zhang L, He X, He X, Lian L, et al. Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways. Mol Med Rep 2014; 9:476-80.
  • Tsai TH, Chuang LT, Lien TJ, Liing YR, Chen WY, Tsai PJ. Rosmarinus officinalis extract suppresses Propionibacterium acnes-induced inflammatory responses. J Med Food 2013; 16:324-33.
  • Mengoni ES, Vichera G, Rigano LA, Rodriguez-Puebla ML, Galliano SR, Cafferata EE, et al. Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 2011; 82: 414-21.
  • Bernardes WA, Lucarini R, Tozatti MG, Souza MG, Silva ML, Filho AA, et al. Antimicrobial activity of Rosmarinus officinalis against oral pathogens: relevance of carnosic acid and carnosol. Chem Biodivers 2010; 7:1835-40.
  • Oluwatuyi M, Kaatz GW, Gibbons S. Antibacterial and resistance modifying activity of Rosmarinus officinalis. Phytochemistry 2004; 65: 3249-54.
  • Bozin B, Mimica-Dukic N, Samojlik I, Jovin E. Antimicrobial and antioxidant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. J Agric Food Chem 2007; 55:7879-85.

KARNOSOL SIÇANLARDA BAĞIRSAK İSKEMİ-REPERFÜZYON MODELİNDE İNFLAMASYON VE BAKTERİYEL TRANSLOKASYONU HAFİFLETİR

Year 2019, Volume: 5 Issue: 2, 105 - 118, 27.06.2019

Abstract

İntestinal iskemi-reperfüzyon hasarı (II/R), önemli morbidite ve mortaliteye sahip bir durumdur. Bu çalışmada, anti-oksidan, anti-enflamatuvar, anti-karsinojenik ve anti-mikrobiyal bir ajan olan karnosolün II/R modeli uygulanan sıçanlarda pro-inflamatuar sitokinler, doku anjiopoietinleri, histopatolojik hasar ve bakteriyel translokasyon üzerindeki koruyucu etkisini göstermek amaçlanmıştır. Otuz erkek Sprague-Dawley sıçanı 3 gruba ayrıldı: kontrol grubu, intestinal iskemi/reperfüzyon grubu (II/R) ve karnosol grubu (II/ R+C). İskemi-reperfüzyon hasarı laparotomi ile sağlandı. Tüm sıçanlara ameliyattan 12 saat önce 1010 koloni oluşturan birim/mililitre E.coli uygulandı. II/R+C grubuna, ameliyattan 3 gün önce başlayarak oral 3 mg/kg/gün karnosol uygulandı. Ameliyat sonrası takipten 72 saat sonra, sıçanlar örnek toplama için yeniden laparotomize edildi. II/R+C grubunun II/R grubuna göre serum TNF-α, IL-1β ve IL-6 düzeyleri anlamlı derecede azalmıştı (sırasıyla p=0.026, 0.006 ve 0.045). II/R grubunun, II/R+C grubuna göre daha şiddetli doku hasarına maruz kaldığı görüldü (p<0.001). II/R+C grubu, II/R grubu ile karşılaştırıldığında, karaciğer, dalak ve mezenterik lenf nodu kültür pozitifliğinin anlamlı düzeyde azalmış olduğu gösterilmiştir. Anjiyopoietin I ve II düzeyleri gruplar arasında benzerdi. Sonuç olarak, karnosol güçlü bir anti-inflamatuar ve anti-mikrobiyal ajandır. Bu çalışmada karnosolun II/R modelinde pro-inflamatuar sitokin profilinin etkili bir şekilde azaltan, histopatolojik hasarı düzelten ve bakteriyel translokasyonu önleyen bir ajan olduğu gösterilmiştir.

Project Number

Financial funding was obtained from Trakya University Scientific Studies Fund.

References

  • Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am 1992; 72:65-83.
  • Sorkine P, Szold O, Halpern P, Gutman M, Greemland M, Rudick V, et al. Gut decontamination reduces bowel ischemia-induced lung injury in rats. Chest 1997; 112:491-5.
  • Schoenberg MH, Beger HG. Reperfusion injury after intestinal ischemia. Crit Care Med 1993; 21:1376-86.
  • Tullis MJ, Brown S, Gewertz BL. Hepatic influence on pulmonary neutrophil sequestration following intestinal ischemia-reperfusion. J Surg Res. 1996; 66: 143-6.
  • Börjesson A, Norlin A, Wang X, Andersson R, Folkesson HG. TNF-alpha stimulates alveolar liquid clearance during intestinal ischemia-reperfusion in rats. Am J Physiol Lung Cell Mol Physiol 2000; 278: L3-12.
  • Simpson R, Alon R, Kobzik L, Valeri CR, Shepro D, Hechtman HB. Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion. Ann Surg 1993; 218: 444-53.
  • Towfigh S, Heisler T, Rigberg DA, Hines OJ, Chu J, McFadden DW, et al. Intestinal ischemia and the gut-liver axis: an in vitro model. J Surg Res 2000; 88:160-4.
  • Turnage RH, Guice KS, Oldham KT. Endotoxemia and remote organ injury following intestinal reperfusion. J Surg Res 1994; 56: 571-8.
  • Köksoy C, Kuzu MA, Kuzu I, Ergün H, Gürhan I. Role of tumour necrosis factor in lung injury caused by intestinal ischaemia-reperfusion. Br J Surg 2001; 88:464-8.
  • Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000; 6: 460-3.
  • Kim I, Moon SO, Park SK, Chae SW, Koh GY. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res 2001; 89:477-9.
  • Pizurki L, Zhou Z, Glynos K, Roussos C, Papapetropoulos A. Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Br J Pharmacol 2003; 139:329-36.
  • Mandriota SJ, Pepper MS. Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res 1998; 83:852-9.
  • Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 2006; 12:235-9.
  • Conesa EL, Valero F, Nadal JC, Fenoy FJ, López B, Arregui B, et al. N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal failure. Am J Physiol Regul Integr Comp Physiol 2001;281: R730-7.
  • Maghsoudi S, Gol A, Dabiri S, Javadi A. Preventive effect of ginger (Zingiber officinale) pretreatment on renal ischemia-reperfusion in rats. Eur Surg Res 2011; 46:45-51.
  • Baud L, Ardaillou R. Reactive oxygen species: production and role in the kidney. Am J Physiol 1986; 251: F765-76.
  • Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970; 101:478-83.
  • Günel E, Cağlayan F, Cağlayan O, Dilsiz A, Duman S, Aktan M. Treatment of intestinal reperfusion injury using antioxidative agents. J Pediatr Surg 1998; 33:1536-9.
  • Tian XF, Yao JH, Zhang XS, Zheng SS, Guo XH, Wang LM, et al. Protective effect of carnosol on lung injury induced by intestinal ischemia/reperfusion. Surg Today 2010; 40:858-65.
  • Yao JH, Zhang XS, Zheng SS, Li YH, Wang LM, Wang ZZ, et al. Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion. World J Gastroenterol 2009; 15:3240-5.
  • Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC, et al. Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects. Biosci Biotechnol Biochem 2007; 71:2223-32.
  • Chen CC, Chen HL, Hsieh CW, Yang YL, Wung BS. Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival. Acta Pharmacol Sin 2011; 32:62-9.
  • Chae IG, Yu MH, Im NK, Jung YT, Lee J, Chun KS, et al. Effect of Rosemarinus officinalis L. on MMP-9, MCP-1 levels, and cell migration in RAW 264.7 and smooth muscle cells. J Med Food 2012; 15:879-86.
  • Yao H, Chen Y, Zhang L, He X, He X, Lian L, et al. Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways. Mol Med Rep 2014; 9:476-80.
  • Tsai TH, Chuang LT, Lien TJ, Liing YR, Chen WY, Tsai PJ. Rosmarinus officinalis extract suppresses Propionibacterium acnes-induced inflammatory responses. J Med Food 2013; 16:324-33.
  • Mengoni ES, Vichera G, Rigano LA, Rodriguez-Puebla ML, Galliano SR, Cafferata EE, et al. Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 2011; 82: 414-21.
  • Bernardes WA, Lucarini R, Tozatti MG, Souza MG, Silva ML, Filho AA, et al. Antimicrobial activity of Rosmarinus officinalis against oral pathogens: relevance of carnosic acid and carnosol. Chem Biodivers 2010; 7:1835-40.
  • Oluwatuyi M, Kaatz GW, Gibbons S. Antibacterial and resistance modifying activity of Rosmarinus officinalis. Phytochemistry 2004; 65: 3249-54.
  • Bozin B, Mimica-Dukic N, Samojlik I, Jovin E. Antimicrobial and antioxidant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. J Agric Food Chem 2007; 55:7879-85.
There are 30 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Özgür Cem Müsri

Serhat Oğuz This is me

Şaban Gürcan This is me

Taner Özgürtaş This is me

Tülin Yalta This is me

Gokhan Tazegul

Fatma Yalçın Müsri

Project Number Financial funding was obtained from Trakya University Scientific Studies Fund.
Publication Date June 27, 2019
Published in Issue Year 2019 Volume: 5 Issue: 2

Cite

APA Müsri, Ö. C., Oğuz, S., Gürcan, Ş., Özgürtaş, T., et al. (2019). CARNOSOL ALLEVIATES INFLAMMATION AND BACTERIAL TRANSLOCATION IN A RAT MODEL OF INTESTINAL ISCHEMIA-REPERFUSION INJURY. International Anatolia Academic Online Journal Health Sciences, 5(2), 105-118.

International Anatolia Academic Online Journal Health Sciences