Role of the antiangiogenetic drug paclitaxel on healing of intestinal anastomosis: an experimental study.

BACKGROUND: The aim of intraperitoneal administration of antineoplastic agents is the prevention of the implantation of tumoral cells after surgical intervention or the treatment of peritoneal carcinomatosis. The efficiency of intraperitoneal administration of paclitaxel, which is also an antiangiogenetic agent, has been investigated recently. The aim of this experimental study was to evaluate, taking into consideration its antiangiogenetic properties, the effects of intraperitoneal paclitaxel on healing of end to end colonic anastomosis. METHODS: 42 rats were allocated to 2 main groups (n = 21 for each group) to be evaluated on postperative day 3 (group A) and postoperative day 7 (group B). Each of the two main groups was divided into 3 subgroups (7 rats each). These subgroups were determined as control and two treatment groups administered paclitaxel in a dose of 2.5 mg/kg and 3.5 mg/kg intraperitoneally. Anastomosed segments of colon were harvested on postoperative day 3 or 7 and evaluated to determine bursting pressure of anastomoses, hydroxyproline levels and neovascularization with CD-31. RESULTS: In both groups, there were no significant differences between control and paclitaxel-treated groups with respect to bursting pressure. The level of hydroxyproline showed a significant decrease in all paclitaxel-treated groups compared with control groups (p = 0.001). Neovascularization was found to be decreased significantly on day 3 in the doses of paclitaxel 2.5 mg/kg (6.4 +/- 1.63) and 3.5 mg/kg (5.89 +/- 1.01) compared with control (8.02 +/- 0.88) (p = 0.029 and p = 0.005, respectively). There were no significant differences in neovascularization in either groups on postoperative day 7. CONCLUSION: We suggest that intraperitoneal administration of paclitaxel during surgical procedure decreases the hydroxyproline content and neovessel formation that are necessary for healing of intestinal anastomosis.

The role of oxygen free radicals in acute renal failure complicating obstructive jaundice: an experimental study.

Oxidant injury is considered to be an important mechanism in the pathophysiology of acute renal failure. It has been thought that decrease in extracellular and intracellular fluid and endotoxemia seen in obstructive jaundice may cause an increase in production of oxygen free radicals and impairment in antioxidant defense mechanism. This study is designed to investigate the possible role of oxidant injury in renal failure seen in jaundiced patients. In this study, 28 rats were divided into four groups: Control (C)(N = 7); Renal ischemia (RI)(N = 7); Obstructive jaundice+renal ischemia (OJ+RI)(N = 7); Obstructive jaundice (OJ)(N = 7). All groups were compared with each other according to renal failure findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px), in blood at 3rd day after ischemia and reperfusion. Renal failure findings monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than RI group (p < 0.05). When compared with RI, in OJ+RI group, increase in XOD activity at 3rd day was statistically significant [0.259 +/- 0.01 U/g (tissue) and 0.362 +/- 0.03 U/g (tissue) respectively] (p < 0.05). SOD and GSH-Px activities of each ischemic group at 3rd day were decreased compared to non-ischemic groups. This fall was significant (p < 0.05). But there was no statistical difference between jaundiced and non-jaundiced groups. Alterations in catalase activities also had no statistical significance. These findings may suggest that the injury induced by oxygen free radicals at re-oxygenation of tissue after ischemia may also play a role in the pathogenesis of acute renal failure developed in obstructive jaundice.