Skip to main content
SpringerLink
Log in

The Effect of Insulin-Like Growth Factor I on Healing of Colonic Anastomoses in Cortisone-Treated Rats

  • Published:
Diseases of the Colon & Rectum

Purpose

This study was designed to investigate whether intraperitoneally injected insulin-like growth factor I is able to protect colonic healing from the adverse effects of hydrocortisone therapy.

Methods

Eighty female Wistar rats were randomized into four groups (20 rats each). After resection of a segment of transverse colon, an end-to-end anastomosis was performed. Hydrocortisone (5 mg/kg body weight) was injected intramuscularly in rats of cortisone (Group B) and insulin-like growth factor I + cortisone (Group D) groups once daily for seven days before and after the operation. Insulin-like growth factor I (2 mg/kg body weight) was intraperitoneally injected in rats of the insulin-like growth factor I (Group C) and the insulin-like growth factor I + Cortisone (Group D) groups immediately after operation and on the second, fourth, and sixth postoperative days. Rats were killed on the seventh postoperative day. Anastomoses were graded macroscopically and histologically, and bursting pressures and anastomotic hydroxyproline levels were recorded. Statistical analyses were performed by using Fisher's exact test for the comparison of proportions and ANOVA for the comparison of means among groups with subsequent post-hoc analysis using Bonferroni correction.

Results

Leakage rate was significantly higher in the cortisone (Group B) group. Bursting pressures were significantly lower in the cortisone group, whereas they were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups (Group C and D). Histology revealed a significant decrease of inflammatory cell infiltration, neoangiogenesis, and fibroblast activity in the cortisone group compared with the control group, whereas these parameters were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups. Hydroxyproline levels were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups.

Conclusions

Hydrocortisone inhibits the healing of colonic anastomoses. However, insulin-like growth factor I given intraperitoneally mediates the deleterious effects of cortisone and protects colonic healing in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

References

  1. I Kanellos K Vasiliadis S Angelopoulos T Tsachalis MG Pramateftakis D Betsis (2004) ArticleTitleAnastomotic leakage following anterior resection for rectal cancer Tech Coloproctol 8 79–81 Occurrence Handle10.1007/s10151-004-0119-8

    Article  Google Scholar 

  2. I Kanellos (2004) ArticleTitleProgress in the treatment of colorectal cancer Tech Coloproctol 8 s1–s2 Occurrence Handle15655586 Occurrence Handle10.1007/s10151-004-0094-0

    Article  PubMed  Google Scholar 

  3. I Kanellos K Blouhos H Demetriades et al. (2004) ArticleTitleThe failed intraperitoneal colon anastomosis after colon resection Tech Coloproctol 8 s53–s55 Occurrence Handle15655643 Occurrence Handle10.1007/s10151-004-0111-3

    Article  PubMed  Google Scholar 

  4. I Kanellos E Zacharakis E Christoforidis H Demetriades D Betsis (2002) ArticleTitleLow anterior resection without protective colostomy Tech Coloproctol 6 153–157 Occurrence Handle12525908 Occurrence Handle1:STN:280:DC%2BD3s%2FhvFCiuw%3D%3D Occurrence Handle10.1007/s101510200035

    Article  PubMed  CAS  Google Scholar 

  5. A Gainant (2000) ArticleTitlePrevention of anastomotic dehiscence in colorectal surgery J Chir (Paris) 137 45–50 Occurrence Handle1:STN:280:DC%2BD3c3ltlWqsg%3D%3D

    CAS  Google Scholar 

  6. M Amoruso D D’Abbicco A Notarnicola A Angrisano M Nacchiero G Martino Bonomo (2001) ArticleTitleEarly colorectal reoperation: risk factors Chir Ital 53 827–833 Occurrence Handle11824058 Occurrence Handle1:STN:280:DC%2BD38%2FpsFGjug%3D%3D

    PubMed  CAS  Google Scholar 

  7. A Cihan M Oguz Z Acun et al. (2004) ArticleTitleComparison of early postoperative enteral nutrients versus chow on colonic anastomotic healing in normal animals Eur Surg Res 36 112–115 Occurrence Handle15007264 Occurrence Handle1:CAS:528:DC%2BD2cXitlyisbg%3D Occurrence Handle10.1159/000076651

    Article  PubMed  CAS  Google Scholar 

  8. A Polat A Nayci G Polat S Aksoyek (2002) ArticleTitleDexamethasone down-regulates endothelial expression of intercellular adhesion molecule and impairs the healing of bowel anastomoses Eur J Surg 168 500–506 Occurrence Handle12549693 Occurrence Handle1:CAS:528:DC%2BD3sXptVOitQ%3D%3D Occurrence Handle10.1080/110241502321116532

    Article  PubMed  CAS  Google Scholar 

  9. S Dinc H Alagol MA Gulcelik et al. (2002) ArticleTitleLocally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment World J Surg 26 1208–1213 Occurrence Handle12205560 Occurrence Handle10.1007/s00268-002-6505-3

    Article  PubMed  Google Scholar 

  10. RS Salcido (2005) ArticleTitleDo anti-inflammatories have a role in wound healing? Adv Skin Wound Care 18 65–66 Occurrence Handle15788902

    PubMed  Google Scholar 

  11. LC Read FM Tomas GS Howarth AA Martin KJ Edson GM Gillespie (1992) ArticleTitleInsulin-like growth factor-I and its N-terminal modified analogues induced marked gut growth in dexamethasone-treated rats J Endocrinol 133 421–431 Occurrence Handle1613443 Occurrence Handle1:CAS:528:DyaK38XisV2ntro%3D

    PubMed  CAS  Google Scholar 

  12. MS Bitar (1997) ArticleTitleInsulin-like growth factor I reverses diabetes-induced wound healing impairment in rats Horm Metab Res 29 283–286

    Google Scholar 

  13. AC Ham ParticleVan der WJ Kort IM Weijma HF Ingh Particlevan den J Jeekel (1991) ArticleTitleEffect of fibrin sealant on the healing colonic anastomosis in the rat Br J Surg 78 49–53 Occurrence Handle1998864

    PubMed  Google Scholar 

  14. HP Ehrlich TK Hunt (1969) ArticleTitleThe effects of cortisone and anabolic steroids on the tensile strength of healing wounds Ann Surg 170 203–206 Occurrence Handle5796705 Occurrence Handle1:CAS:528:DyaF1MXkvFylt7g%3D Occurrence Handle10.1097/00000658-196908000-00007

    Article  PubMed  CAS  Google Scholar 

  15. JD Philips CS King EW Fonkalsrud H Zeng H Dindar (1992) ArticleTitleEffect of chronic corticosteroid and vitamin A on the healing of intestinal anastomoses Am J Surg 163 71–77 Occurrence Handle10.1016/0002-9610(92)90255-P

    Article  Google Scholar 

  16. JM Villar AP Martinez MT Villegas et al. (2005) ArticleTitleSurgical options for malignant left-sided colonic obstruction Surg Today 35 275–281 Occurrence Handle15815842 Occurrence Handle10.1007/s00595-004-2931-1

    Article  PubMed  Google Scholar 

  17. O Zmora SD Wexner L Hajjar et al. (2003) ArticleTitleTrends in preparation for colorectal surgery: survey of the members of the American Society of Colon and Rectal Surgeons Am Surg 69 150–154 Occurrence Handle12641357

    PubMed  Google Scholar 

  18. D Demetriades JA Murray LS Chan et al. (2002) ArticleTitleHandsewn versus stapled anastomosis in penetrating colon injuries requiring resection: a multicenter study J Trauma 52 117–121 Occurrence Handle11791061 Occurrence Handle10.1097/00005373-200201000-00020

    Article  PubMed  Google Scholar 

  19. TL Buchmiller-Crair CS Kim NH Won HL Chopourian KS Shaw EW Fonkalsrud (2000) ArticleTitleEffect of acute anemia on the healing of intestinal anastomoses in the rabbit J Trauma 51 363–368

    Google Scholar 

  20. TI Petersen P Kissmeyer-Nielsen A Flyvbjerg S Laurberg H Christensen (1996) ArticleTitleEffect of insulin-like growth factor I (IGF-I) administration on the healing of colonic anastomoses in rats Int J Colorectal Dis 11 19–24 Occurrence Handle8919336 Occurrence Handle1:STN:280:DyaK2s%2FnvVCisA%3D%3D Occurrence Handle10.1007/BF00418850

    Article  PubMed  CAS  Google Scholar 

  21. TR Eubanks JJ Greenberg PB Dobrin FJ Harford RL Gamelli (1997) ArticleTitleThe effects of different corticosteroids on the healing colon anastomosis and cecum in a rat model Am Surg 63 266–269 Occurrence Handle9036897 Occurrence Handle1:STN:280:DyaK2s7ovVeisA%3D%3D

    PubMed  CAS  Google Scholar 

  22. AE Schindler (2004) ArticleTitleGonadotropin-releasing hormone agonists for prevention of postoperative adhesions: an overview Gynecol Endocrinol 19 51–55 Occurrence Handle15625774 Occurrence Handle1:CAS:528:DC%2BD2cXnslWrs7w%3D Occurrence Handle10.1080/09513590310001651795

    Article  PubMed  CAS  Google Scholar 

  23. T Kucukozkan B Ersoy D Uygur C Gundogdu (2004) ArticleTitlePrevention of adhesions by sodium chromoglycate, dexamethasone, saline and aprotinin after pelvic surgery ANZ J Surg 74 1111–1115 Occurrence Handle15574156 Occurrence Handle10.1111/j.1445-1433.2004.03261.x

    Article  PubMed  Google Scholar 

  24. A Cihan F Armutcu BH Ucan et al. (2003) ArticleTitleComparison of the measurement methods of bursting pressure of intestinal anastomoses Hepatogastroenterology 50 s232–s234

    Google Scholar 

  25. T Colak A Nayci G Polat et al. (2003) ArticleTitleEffects of trapidil on the healing of colonic anastomoses in an experimental rat model ANZ J Surg 73 916–921 Occurrence Handle14616570 Occurrence Handle10.1046/j.1445-2197.2003.02683.x

    Article  PubMed  Google Scholar 

  26. B Egger R Inglin J Zeeh O Dirsch Y Huang MW Buchler (2001) ArticleTitleInsulin-like growth factor I and truncated keratinocyte growth factor accelerate healing of left-sided colonic anastomoses Br J Surg 88 90–98 Occurrence Handle11136318 Occurrence Handle1:STN:280:DC%2BD3M7isFGmsA%3D%3D Occurrence Handle10.1046/j.1365-2168.2001.01617.x

    Article  PubMed  CAS  Google Scholar 

  27. N Reinmuth F Fan W Liu et al. (2002) ArticleTitleImpact of insulin-like growth factor receptor-I function on angiogenesis, growth, and metastasis of colon cancer Lab Invest 82 1377–1389 Occurrence Handle12379772 Occurrence Handle1:CAS:528:DC%2BD38Xns1ClsrY%3D

    PubMed  CAS  Google Scholar 

  28. ED Rabinovsky R Draghia-Akli (2004) ArticleTitleInsulin-like growth factor I plasmid therapy promotes in vivo angiogenesis Mol Ther 9 46–55 Occurrence Handle14741777 Occurrence Handle1:CAS:528:DC%2BD2cXntVOjtg%3D%3D Occurrence Handle10.1016/j.ymthe.2003.10.003

    Article  PubMed  CAS  Google Scholar 

  29. JG Simmons JB Pucilowska TO Keku PK Lund (2002) ArticleTitleIGF-I and TGF-beta1 have distinct effects on phenotype and proliferation of intestinal fibroblasts Am J Physiol Gastrointest Liver Physiol 283 G809–G818 Occurrence Handle12181198 Occurrence Handle1:CAS:528:DC%2BD38XntFOmt7Y%3D

    PubMed  CAS  Google Scholar 

  30. JP Lake E Firoozmand JC Kang et al. (2004) ArticleTitleEffect of high-dose steroids on anastomotic complications after proctocolectomy with ileal pouch–anal anastomoses J Gastrointest Surg 8 547–551 Occurrence Handle15239989 Occurrence Handle10.1016/j.gassur.2004.01.002

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Vicky Kanellou, B.A. Hons., M.A., for assistance and also Anna-Bettina Haidich, Ph.D., for statistical analysis.

Author information

Authors and Affiliations

  1. 4th Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece

    I. Mantzoros M.D., Ph.D., I. Kanellos M.D., Ph.D., S. Angelopoulos M.D., Ph.D., G. Koliakos M.D., Ph.D., M. G. Pramateftakis M.D., D. Kanellos M.D., E. Zacharakis M.D., T. Zaraboukas M.D., Ph.D. & D. Betsis M.D., Ph.D.

  2. 4th Department of Surgery, Aristotle University of Thessaloniki, G. Papanikolaou General Hospital, Exohi, Thessaloniki, 57010, Greece

    I. Mantzoros M.D., Ph.D.

Authors
  1. I. Mantzoros M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Kanellos M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Angelopoulos M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Koliakos M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. G. Pramateftakis M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Kanellos M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. Zacharakis M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. Zaraboukas M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D. Betsis M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Mantzoros M.D., Ph.D..

About this article

Cite this article

Mantzoros, I., Kanellos, I., Angelopoulos, S. et al. The Effect of Insulin-Like Growth Factor I on Healing of Colonic Anastomoses in Cortisone-Treated Rats. Dis Colon Rectum 49, 1431–1438 (2006). https://doi.org/10.1007/s10350-006-0603-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10350-006-0603-5

Key words

Search

Navigation