Effects of celastron, a novel NF-?B inhibitor, on anastomotic wound healing in previously irradiated colon radiation bursting pressure, hydroxiproline levels

Surgical resection is the gold standart procedure in colorectal cancer. After surgical resection, local recurrence rate is mainly declared as about %30 (28). Nowadays preoperative radiotheraphy is becoming commonly accepted in rectum cancer treatment protocols. In lots of study it is shown that preoperative RT can perform rectum cancer to resectable form and can decrease the rate of metastases of lenf nods and local recurrence (1, 6, 8, 72). On the other hand this method have some side affects. Due to these side affects, wound healing can be delayed and an increase in anastomotic leakage rate is noted (82). Anastomotic leakage rates emerges between %0 and % 35.In this study we used 64 wister albino male rat (main weight 250-300 gr). Colon resection and re-anastomose is performed in Group I, the control group. By using a lineer accelerator that produces 6MV ray in pre-anastomose radiotherapy, for five days, 5 Gy per day, totally 25 Gy, in standart fractions, is given in Group II, RT group. For 5 days 1/10 dimethyl formamide (DMF), that dissolved in the PBS (pH: 7,2) solution , 1mg/ml is applied to rats in Group III, celastrol group. It is given to rats, 3mg/kg/days by the introperitoneal way during preoperative radiotheraphy process, for five days. Preoperative radiotheraphy and celastrol is given for 5 days in Group 4, RT+ celastrol group. In each group, on 3rd and 7th days postoperative bursting pressures are measured and samples are taken from anastomose and rats are sacrificed. The ones sacrificed on day 3 are named as `a?, and the others sacrificed on day 7 are named as `b?.The rate of morbidity and mortality in rats are calculated. Anastomose bursting pressures and the hydroxiproline levels and histopathologic evaluations are measured. The histopathologic analyse of wound healing in anastomosic tissue is made, and the activity of NF-?B by ELISA is measured.For statistical evaluation the method of ANOVA is used and P < 0.05 is taken as significant.When we compared the group 1 with group 2 on the 3th and 7th days, bursting pressures are statistically significant, group 1 levels are higher than group 2 (P < 0.05 and P < 0.01). On the other hand, when we compared the group 1 with the group 3 and 4, there are no statistically significant difference (P > 0.05).When we compared the group 1 with group 2 on the 3th and 7th days, hydroxyproline levels are statistically significant, group 1 levels are higher than group 2 (on the 3rd day, to 0.323 µg /mg, 0.255 µg /mg; P < 0.05 and on the 7th day, to 0.352 µg /mg, 0.271 µg /mg; P < 0.01) . On the other hand, when we compared the group 1 with the group 3 and 4, there are no statistically significant difference (P > 0.05 ).When we compared the group 1 with group 2 on the 3th and 7th days, NF-kB levels are statistically significant, group 2 levels are higher than group 1 (P < 0.05). On the other hand, when we compared the group 1 with the group 3 and 4, there are no statistically significant difference (P > 0.05).As a result, in our study, it is obtained that celastrol can be supportive especially in colorectal surgery, in anastomose healing after peroperative or postoperative radiotheraphy.