Effect of reactive oxygen species scavengers,antiinflammatory drugs,and calcium-channel blockers on carbon dioxide pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model

Background Postoperative adhesions are a clinical problem. They can cause female infertility, intestinal obstruction, chronic pelvic pain, and difficulties at the time of reoperation. A variety of approaches described to prevent adhesions have shown variable and inconsistent results. Therefore, this study aimed to evaluate most known substances in a laparoscopic mouse model to obtain quantitative and comprehensive information on adhesion prevention. Specifically, this first study aimed to investigate the effects of reactive oxygen species (ROS) scavengers, antiinflammatory agents, and a calcium-channel blocker on pneumoperitoneum-enhanced adhesions. Methods Adhesions were induced during laparoscopy in BALB/c female mice by creation of a bipolar lesion. Carbon dioxide (CO₂) pneumoperitoneum was maintained for 60 min using humidified CO₂. Six experiments were conducted to evaluate the effects of ROS scavengers (superoxide dismutase [SOD], catalase, melatonin, and ascorbic acid), antiinflammatory agents (dexamethasone, tenoxicam, ibuprofen, parecoxib, nimesulide, anti–tumor necrosis factor [TNF]-alpha), and a calcium-channel blocker (diltiazem). Adhesions were scored after 7 days during laparotomy. Results Adhesions were reduced by SOD (p < 0.01, proc general linear methods (GLM) of experiments 1 and 2), diltiazem (p = 0.05, Wilcoxon), and dexamethasone (p < 0.03), but not by nonsteroidal antiinflammatory drugs (NSAIDs) nor by anti–TNF-alpha. When all the experiments were grouped for analysis, adhesions also decreased with one and three doses of SOD (p < 0.01 and p < 0.01, respectively) and with one and three doses of ascorbic acid (p < 0.02 and p = 0.05, respectively). Conclusions These experiments confirm that SOD, diltiazem, and dexamethasone can decrease adhesion formation. The absence of effect from the other antiinflammatory drugs and anti-TNF-alpha is surprising. Presented at the XV Annual Congress of the International Society for Gynecological Endoscopy (ISGE), 29 March to 1 April, 2006, Buenos Aires, Argentina