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

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Abstract

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.

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Acknowledgments

We thank R. Pijnenborg, PhD, Ms. R. Van Bree, J. Verguts, MD, L. Ret, MD, C. De Cicco, MD, and L. Vercruysse, MSc (Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg) for their help. This study was supported by Onderzoeks Toelagen Katholieke Universiteit Leuven (Leuven, Belgium grant TBA/00/27) and in part by Karl Storz Endoscopy (Tuttlingen, Germany).

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  1. Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Herestraat 49 Bus 611, B3000, Leuven, Belgium

    M. M. Binda, A. Bastidas & P. R. Koninckx

  2. Centre for Gynaecological Endoscopy (Cendogyn), Centro Médico La Costa, Asunción, Paraguay

    C. R. Molinas

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  1. M. M. Binda
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Correspondence to M. M. Binda.

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Binda, M.M., Molinas, C.R., Bastidas, A. et al. Effect of reactive oxygen species scavengers, antiinflammatory drugs, and calcium-channel blockers on carbon dioxide pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model. Surg Endosc 21, 1826–1834 (2007). https://doi.org/10.1007/s00464-007-9296-7

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