Effects of soluble fiber on matrix metalloproteinase-2 activity and healing of colon anastomosis in rats given radiotherapy.
ABSTRACT Soluble fiber is fermented by colonic microflora yielding short-chain fatty acids (SCFAs) in the colon. We aimed to investigate the effect of oral administration of soluble fiber on healing of anastomosis and matrix metalloproteinase-2 activity in radiotherapy received colonic anastomosis.
Eighty-four Wistar rats were divided into six groups. All rats were performed a left colonic resection with end-to-end anastomosis. Group I received rat cow. Group II received soluble fiber orally for five consecutive days preoperatively as well as 3rd and 6th days postoperatively. Group III received SCFAs via rectum for five consecutive days preoperatively. Group IV received irradiation to the pelvis at a total dose of 24 Gy on the 10th and 5th days before the operation. Group V was exposed to irradiation like the rats in Group IV and oral treatment like the rats in Group II. Group VI received irradiation like the rats in Group IV and transrectal treatment like the rats in Group III. On the 3rd and 7th postoperative days, all the rats were anesthetized to evaluate the anastomosis healing clinically, histologically and biochemically.
Third and 7th day bursting pressures of the rats that were fed with a normal diet and exposed to radiotherapy were significantly decreased (P<0.001). Bursting pressures of Groups V and VI on the 7th day were significantly higher than the control group's bursting pressures (P<0.05). Hydroxyproline levels of Group IV were significantly decreased (P<0.001). Following oral soluble fiber and transrectal administration of SCFAs, these low levels reached to the levels of control radiotherapy group. Matrix metalloproteinase-2 activity of all the rats that were exposed to radiotherapy was higher than the control group (P<0.001). Matrix metalloproteinase-2 enzyme levels in the Groups V and VI were lower than the ones in the Group IV (P<0.001). The histologic parameters of anastomotic healing such as epithelial regeneration, exudate, necrosis, and fibroblast levels were significantly improved by the use of oral soluble fiber and transrectal SCFAs treatment.
Undesirable effects of preoperative radiotherapy on mechanical, histological and biochemical parameters can be overcome by oral soluble fiber. Oral soluble fiber administration has similar positive effects like the transrectal administration of the SCFA's.
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ABSTRACT: 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. 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. 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. 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.Journal of Surgical Research 11/2011; 171(1):355-60. · 2.02 Impact Factor
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ABSTRACT: Abstract Background: Neoadjuvant radiotherapy in rectal cancer could interfere with anastomotic healing. We investigated the effects of preoperative oral administration of Benefiber on the healing irradiated colonic anastomosis. Methods: Forty male Wistar rats were divided into four groups. Group I (control group), Group II (Benefiber® pretreatment group), Group III (preoperative radiotherapy group) and Group IV (preoperative radiotherapy and Benefiber® pretreatment group). All animals underwent 1 cm left colon resection and primary anastomosis. On the 3rd and 7th postoperative days, all the rats were anesthetized to assess the anastomotic healing clinically, mechanically, histologically and biochemically. Results: The mean bursting pressure was significantly lower in-group III and significantly higher in-group II on day 7. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative Benefiber® on day 7. The amount of acid-soluble collagen concentrations significantly increased in-group IV compared to group III on day 3. The amount of salt-soluble collagen concentrations significantly increased in group II compared to group III on day 3. Conclusions: Colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but orogastric feeding with Benefiber may improve the healing process.Journal of Drug Targeting 12/2013; · 2.77 Impact Factor
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ABSTRACT: Anastomotic dehiscence is one of the most severe complications of colorectal surgery. Gaining insight into the molecular mechanisms responsible for the development of anastomotic dehiscence following colorectal surgery is important for the reduction of postoperative complications. Based on the close relationship between surgical stress and oxidative stress, the present study aimed to determine whether a correlation exists between increased levels of reactive oxygen species and colorectal anastomotic dehiscence. Patients who underwent surgical resection for colorectal cancer were divided into three groups: patients with anastomotic dehiscence (group 1); patients without dehiscence who underwent neoadjuvant radiochemotherapy (group 2); and patients without anastomotic dehiscence who did not undergo neoadjuvant radiochemotherapy (group 3). Quantitative polymerase chain reaction and real-time polymerase chain reaction assays were performed to measure nuclear DNA and mitochondrial DNA (mtDNA) content, and possible oxidative damage to nonmalignant colon and rectal tissues adjacent to the anastomoses. mtDNA content was reduced in the colon tissue of patients in groups 1 and 2. Rectal mtDNA was found to be more damaged than colonic mtDNAs in all groups. The 4977 bp common deletion was observed in the mtDNA of tissues from both the colon and rectum of all patients. Patients in groups 1 and 2 were more similar to one another than to group 3, probably due to higher levels of reactive oxygen species in the mitochondria; the greater damage found in the rectum suggests that dehiscence originates primarily from the rectal area. The present study of mtDNA analyses of normal human colon and rectal tissues from patients with colorectal cancer is among the first of its kind.Canadian journal of gastroenterology = Journal canadien de gastroenterologie 08/2011; 25(8):433-9. · 1.53 Impact Factor