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.
Binda
M M
MM
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Herestraat 49 Bus 611, B3000, Leuven, Belgium. MariaMercedes.Binda@uz.kuleuven.ac.be
Molinas
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CR
Bastidas
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A
Koninckx
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PR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002245:Carbon Dioxide; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D010535:Laparoscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011028:Pneumoperitoneum, Artificial; D017382:Reactive Oxygen Species / Q000627:therapeutic use*; D000267:Tissue Adhesions / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002245:Carbon Dioxide