Abstract
Objective: Our aim was to explore the effects of short bowel syndrome (SBS) on CD14 mRNA expression in the liver and examine ultrastructural and biochemical changes in a rat model of total parenteral nutrition (TPN) independent SBS.
Material and Methods: Male Wistar Albino rats, weighing 180 to 220 g (n=37) were randomly divided into two groups as sham operated (n=16) and short bowel syndrome (n=21). Division and re-anastomosis of the bowel 15 cm proximal to the ileocecal junction was performed in sham operated animals. 75% of the small intestine was resected in the short bowel syndrome group. All animals were pair-fed. CD14 mRNA expression was evaluated semiquantitatively via RTPCR. Concomitantly, liver function test were performed and ultrastructural changes in the liver were evaluated.
Results: There was no statistical significant difference regarding liver function tests. There were no significant differences for inflammation, fibrosis and steatosis on histological examination of liver. Cholestasis was more prominent in the SBS group (p<0.05). There were marked ultrastructural changes on electron microscopy. Microvilli canaliculus length, presence of luminal granular biliary material and luminal length of canaliculus were increased in the SBS group (p<0.05). CD14 expression was significantly increased in the liver in the SBS group (p<0.05). The correlation between the ultrastructural changes and CD14 mRNA expression was also prominent (p<0.05)
Conclusion: Cholestasis was demonstrated ultrastructurally in this rat model of TPN independent SBS. Increased expression of CD14 mRNA in the SBS group supports that these changes might occur because of portal venous endotoxemia
Keywords: Cholestasis, Endotoxemia, Hepatic failure, PCR, Short bowel syndrome
References
- 1. Btaiche IF, Khalidi N. Parenteral nutrition-associated liver
- complications in children. Pharmacotherapy 2002;22:188-211.
- 2. Warner B. Short- bowel syndrome. In: Grosfeld JL, O’Neill JA Jr,
- Coran AG, Fonkalsrud EW (eds). Principles of Pediatric Surgery. 6
- ed. Pennsylvania PA: Mosby Elsevier, 2006:1369-82.
- 3. Goulet O, Ruemmele F, Lacaille F, Colomb V. Irreversible intestinal
- failure. J Pediatr Gastroenterol Nutr 2004;38:250-69.
- 4. Forchielli ML, Richardson D, Folkman J, Gura K, Lo CW. Better living
- through chemistry, constant monitoring, and prompt interventions:
- 26 years on home parenteral nutrition without major complications.
- Nutrition 2008;24:103-7.
- 5. Stanko RT, Nathan G, Mendelow H. Development of hepatic
- cholestasis and fibrosis in patients with massive loss of intestine
- supported by prolonged parenteral nutrition. Gastroenterology
- 1987;92:197-202.
- 6. Sondheimer JM, Asturias E, Cadnapaphornchai M. Infection and
- cholestasis in neonates with intestinal resection and long -term
- parenteral nutrition. J Pediatr Gastroenterol Nutr 1998;27:131-7.
- 7. Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral
- nutrition- dependent children with short bowel syndome. J Pediatr
- Surg 1997;32:473-5.
- 8. Fong Y, Marano MA, Barber A, He W, Moldawer LL, Bushman ED,
- et al. Total parenteral nurition and bowel rest modify the metabolic
- response to endotoxin in humans. Ann Surg 1989;210:449-56.
- 9. Trauner M, Fickert P, Stauber RE. Inflammation- induced
- cholestasis. J Gastroenterol Hepatol 1999;14:946-59.
- 10. Owings E, Georgeson K. Management of cholestasis in infants
- with very low birth weight. Semin Pediatr Surg 2000;9:96-102.
- 11. Zeuzem S. Gut- liver axis. Int J Colorectal Dis 2000;15:59-82.
- 12. Jarvelainen HA, Fang C, Ingelman- Sundberg M, Lindros KO. Effect
- of chronic coadministration of endotoxin and ethanol on rat liver
- pathology and proinflammatory and anti- inflammatory cytokines.
- Hepatology 1999;29:1503-10.
- 13. Hua Z, Sergi C, Nation PN, Wizzard PR, Ball RO, Pencharz PB,
- et al. Hepatic ultrastructure in a neonatal piglet model of intestinal
- failure- associated liver disease. J Electron Microsc (Tokyo)
- 2012;61:179-86.
- 14. Kemp R, Correia RB, Sankarankutty AK, dos Santos JS, Modena
- JL, Mente ED, et al. Liver disease associated with intestinal failure
- in small bowel syndrome. Acta Cir Bras 2006;21:67-71.
- 15. Lukkari TA, Jarvelainen HA, Oinonen T, Kettunen E, Lindros KO.
- Short- term ethanol exposure increases the expression of Kupffer
- cell CD14 receptor and lipopolysaccharide binding protein in rat
- liver. Alcohol & Alcoholism 1999;3:311-9.
- 16. Mogilner JG, Srugo I, Lurie M, Shaoul R, Coran AG, Shiloni
- E, et al. Effect of probiotics on intestinal regrowth and bacterial
- translocation after massive small bowel resection in a rat. J Pediatr
- Surg 2007;42:1365-71.
- 17. Aprahamian CJ, Chen M, Yang Y, Lorenz RG, Harmon CM. Twohit rat model of short bowel syndrome and sepsis: Independent of
- total parenteral nutrition, short bowel syndrome is proinflammatory
- and injurious to the liver. J Pediatr Surg 2007;42:992-7.
- 18. Antal- Szalmas P. Evaluation of CD14 in host defence. Eur J Clin
- Invest 2000;30:167-79.
- 19. Takai N, Kataoka M, Higuchi Y, Matsuura K, Yamamoto S. Primary
- structure of rat CD14, cytokine, an NO synhase mRNA expression
- in mononuclear phagocyte system cells in response to LPS. J
- Leukoc Biol 1997;61:736-44.
- 20. Ziegler- Heitbrock H, Ulevitch RJ. CD 14: Cell surface receptor and
- differentiation marker. Immunol Today 1993;14:121-5.
- 21. Bellezzo JM, Britton RS, Bacon BR, Fox ES. LPS-mediated
- NF-kappa beta activation in rat Kupffer cells can be induced
- independently of CD14. Am J Physiol 1996;270:956-61.
- 22. Lichtman SN, Wang J, Lemasters JJ. LPS receptor CD14
- participates in release of TNF-alpha in RAW 264.7 and peritoneal
- cells but not in Kupffer cells. Am J Physiol 1998;275:39-46.
- 23. Matsuura K, Ishida T, Setoguchi M, Higuchi Y, Akizuki S, Yamamoto
- S. Upregulation of mouse CD14 expression in Kupffer cells by
- lipopolysaccharide. J Exp Med 1994;179:1671-6.
- 24. Su GL, Goyert SM, Fan MH, Aminlari A, Gong KQ, Klein RD, et al.
- Activation of human and mouse Kupffer cells by lipopolysaccharide
- is mediated by CD14. Am J Physiol Gastrointest Liver Physiol
- 2002;283:640-5.
- 25. Andorsky DJ, Lund DP, Lillehei CW, Jacsic T, Dicanzio J, Richardson
- DS, et al. Nutritional and other postoperative management of
- neonates with short bowel syndrome correlates with clinical
- outcomes. J Pediatr 2001;139:27-33.