Effects of nuclear factor-κB inhibitors on colon anastomotic healing in rats.
BACKGROUND
Nuclear factor (NF)-κB plays an essential role in inflammation. We tested this role by administering NF-κB-inhibitors into rats undergoing a well-established model of colonic anastomotic healing.


METHODS
Wistar rats underwent laparotomy, descending colonic transection, and handsewn reanastomosis. The animals were randomized to receive either a selective NF-κB inhibitor (parthenolide 0.5 mg/kg or resveratrol 0.5 mg/kg) or an equal volume of water by gavages before operation and then daily after surgery. Animals were sacrificed either immediately after anastomotic construction (d 0) or at the third, fifth, or seventh postoperative day.


RESULTS
Both parthenolide and resveratrol treatment led to early significant increases in plasma levels of IL-6. On d 7, hydroxyproline levels were significantly higher in the parthenolide and resveratrol groups. A similar pattern was observed with the bursting pressure. In contrast, gelatinase activity (MMP-2 and MMP-9 expression) was significantly higher in the control group on postoperative d 3. On d 3, expression of NF-κB activity was up-regulated in the anastomotic area. Both parthenolide and resveratrol completely attenuated NF-κB activity. Study groups also developed more marked inflammatory cell infiltration and collagen deposition on histology analysis.


CONCLUSIONS
Parthenolide and resveratrol significantly improved healing and mechanical stability of colonic anastomoses in rats during the early postoperative period. Both agents may be acting to accelerate the host reparative process as well as to enhance protection of the anastomotic wound bed.
Bedirli
Abdulkadir
A
Department of General Surgery, Gazi University Medical School, Ankara, Turkey. bedirlia@gazi.edu.tr
Salman
Bulent
B
Pasaoglu
Hatice
H
Ofluoglu
Ebru
E
Sakrak
Omer
O
D000714:Anastomosis, Surgical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003106:Colon / Q000502:physiology* / Q000601:surgery*; D004751:Enteritis / Q000188:drug therapy / Q000276:immunology; D006909:Hydroxyproline / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007813:Laparotomy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D023421:Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012717:Sesquiterpenes / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D016328:NF-kappa B; D012717:Sesquiterpenes; D013267:Stilbenes; C002669:parthenolide; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol; D006909:Hydroxyproline