Postoperative Peritoneal Adhesion Formation Research Articles

A Graphene Composite Film Based Wearable Far-Infrared Therapy Apparatus (GRAFT) for Effective Prevention of Postoperative Peritoneal Adhesion.

Postoperative peritoneal adhesion (PPA) is the most frequent complication after abdominal surgery. Current anti-adhesion strategies largely rely on the use of physical separating barriers creating an interface blocking peritoneal adhesion, which cannot reduce inflammation and suffers from limited anti-adhesion efficacy with unwanted side effects. Here, by exploiting the alternative activated macrophages to alleviate inflammation in adhesion development, a flexible graphene-composite-film (F-GCF) generating far-infrared (FIR) irradiation that effectively modulates the macrophage phenotype toward the anti-inflammatory M2 type, resulting in reduced PPA formation, is designed. The anti-adhesion effect of the FIR generated by F-GCF is determined in the rat abdominal wall abrasion-cecum defect models, which exhibit reduced incidence and area of PPA by 67.0% and 92.1% after FIR treatment without skin damage, significantly superior to the clinically used chitosan hydrogel. Notably, within peritoneal macrophages, FIR reduces inflammation reaction and promotes tissue plasminogen activator (t-PA) level via the polarization of peritoneal macrophages through upregulating Nr4a2 expression. To facilitate clinical use, a wirelessly controlled, wearable, F-GCF-based FIR therapy apparatus (GRAFT) is further developed and its remarkable anti-adhesion ability in the porcine PPA model is revealed. Collectively, the physical, biochemical, and in vivo preclinical data provide compelling evidence demonstrating the clinical-translational value of FIR in PPA prevention.

What is the impact of intraperitoneal surfactant administration against postoperative intraabdominal adhesion formation? an experimental study.

Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it was aimed herein to investigate the effect of intraperitoneal surfactant application on preventing postoperative peritoneal adhesion formation in a uterine horn adhesion model. Twenty-one Wistar albino rats were randomly divided into 3 groups (G1-G3), as follows: G1 (n = 7): control group. The abdomen was opened and then closed; G2 (n = 7): adhesion group. The abdomen was opened. Then, a 2-cm linear incision was made over the right uterine horn, 2 mL of isotonic saline was administered intraperitoneally, and the abdomen was closed; and G3 (n = 7): treatment group. The abdomen was opened, a 2-cm linear incision was made over the right uterine horn, 2 mL (70 mg/kg) of surfactant was administered intraperitoneally, and the abdomen was closed. After 15 days, the rats were euthanized, the abdomens were reopened, and adhesion scoring was performed. After the right uterine horns were removed and fixed with 10% formalin, appropriate sections were taken from the traumatized tissue, stained with Masson's trichrome, and fibrosis and inflammation scoring were performed. The adhesion area and intensity were significantly higher in G2 than in G1 and G3 (p = 0.001) and were similar in G1 and G3 (p = 0.165). While fibrosis and inflammation were significantly higher in G2 than in G1 and G3 (p = 0.001), there was no difference between G1 and G3 (p = 0.5). Intraperitoneal surfactant administration at a dose of 70 mg/kg was found to be effective in preventing intraabdominal adhesion formation in a rat uterine horn model.

Quercetin inhibits mesothelial-mesenchymal transition and alleviates postoperative peritoneal adhesions by blocking the TGF-β1/PI3K/AKT pathway

Ethnopharmacological relevanceCarthami flos is a dried flower of the Asteraceae plant Carthamus tinctorius (L.). Danhong injection, composed of Carthami flos and Danshen can prevent the formation of postoperative peritoneal adhesions. Quercetin (QUE), an active compound of Carthami flos, has also been proved to prevent postoperative abdominal and uterine cavity adhesions. However, whether QUE is the key component in Carthami flos and the mechanism in preventing postoperative peritoneal adhesions has not been studied. Aim of the studyTo predict whether QUE is the key molecule in Carthami flos and explore the effect and mechanism of QUE in preventing postoperative peritoneal adhesions. Materials and methodsDrug composition and target analysis was used to predict the key component in Carthami flos. The method of cecum-sidewall abrasion was used to establish adhesion models, and the antiadhesion effect of QUE was evaluated with the adhesion scoring system. Network pharmacology was used to predict the targets and potential mechanism of QUE in preventing adhesion. The mechanism was further verified by immunofluorescence, Western blot, wound healing experiment, and molecular docking. ResultsQuercetin was predicted to be the key to preventing postoperative peritoneal adhesions in Carthami flos. Animal experiments revealed that QUE effectively ameliorated adhesions and reduced the expression of mesothelial-mesenchymal transition (MMT) related markers and TGF-β1. Moreover, the TGF-β1/PI3K/AKT pathway was predicted via protein-protein interaction and Kyoto encyclopedia of Genes and Genomes enrichment analysis to play a crucial part in preventing adhesion by QUE. Furthermore, in vitro experiments and molecular docking demonstrated that QUE could block the TGF-β1/PI3K/AKT pathway through forming a stable combination with TβR-II, thereby inhibiting MMT and ameliorating peritoneal adhesion. ConclusionsQUE can not only reduce postoperative TGF-β1 but also block the TGF-β1/PI3K/AKT pathway to inhibit MMT of mesothelial cells, and finally alleviate postoperative peritoneal adhesions. These findings may provide insights towards development of a safe and effective anti-adhesive drug for prevention of postoperative peritoneal adhesions.

Multifunctional Fluorinated Lubricant Infused Poly(4-hydroxybutyrate) (P4HB) Membranes for Full Thickness Abdominal Wall Defect Repair.

Abdominal wall defect caused by surgical trauma, congenital rupture, or tumor resection may result in hernia formation or even death. Tension-free abdominal wall defect repair by using patches is the gold standard to solve such problems. However, adhesions following patch implantation remain one of the most challenging issues in surgical practice. The development of new kinds of barriers is key to addressing peritoneal adhesions and repairing abdominal wall defects. It's already well recognized that ideal barrier materials need to have good resistance to nonspecific protein adsorption, cell adhesion, and bacterial colonization for preventing the initial development of adhesion. Herein, electrospun poly(4-hydroxybutyrate) (P4HB) membranes infused with perfluorocarbon oil were used as physical barriers. The oil-infused P4HB membranes can greatly prevent protein attachment and reduce blood cell adhesion in vitro. We further showed that the perfluorocarbon oil-infused P4HB membranes can reduce bacterial colonization. The in vivo study revealed that perfluoro-(decahydronaphthalene) infused P4HB membranes can significantly prevent peritoneal adhesions in the classic abdominal wall defects model and accelerate defect repair, as evidenced by gross examination and histological evaluation. This work provides a safe fluorinated lubricant-impregnated P4HB physical barrier to inhibit the formation of postoperative peritoneal adhesions and efficiently repair soft-tissue defects. This article is protected by copyright. All rights reserved.

Rosmarinic acid prevents post-operative abdominal adhesions in a rat model

This study aims to determine the effects of rosmarinic acid which involved the mechanisms to decrease the postoperative peritoneal adhesion formation in rats. Various incisions and removing a 1 × 1 cm piece of peritoneum was used to induce the peritoneal adhesions. Experimental groups were as follows: 1—Sham group. 2—Control group: Peritoneal adhesions were induced and no treatments were performed. 3—Treatment groups: Following inducing peritoneal adhesions, animals received rosmarinic acid with 50 and 70 mg/kg dosage, respectively. Macroscopic examination of adhesions indicated that adhesion bands were reduced in both treatment groups compared to the control group. Moreover, the adhesion score was decreased in both treatment groups on day 14. Inflammation and fibroblast proliferation were both reduced in the treatment groups on day 14. TGF-β1, TNF-α, and VEGF were all evaluated by western blot and immunohistochemistry on days 3 and 14. Treatment groups reduced inflammatory cytokines on days 3 and 14. The treatment group with a 70 mg/kg dosage decreased TGF-β1 and TNF-α levels more than the other treatment group. The administration of rosmarinic acid significantly reduced MDA and increased CAT levels. In conclusion, the rosmarinic acid was effective to reduce the adhesion bands, inflammatory cytokines, angiogenesis, and oxidative stress.

Elucidating the Novel Mechanism of Ligustrazine in Preventing Postoperative Peritoneal Adhesion Formation.

Postoperative peritoneal adhesion (PPA) is a major clinical complication after open surgery or laparoscopic procedure. Ligustrazine is the active ingredient extracted from the natural herb Ligusticum chuanxiong Hort, which has promising antiadhesion properties. This study is aimed at revealing the underlying mechanisms of ligustrazine in preventing PPA at molecular and cellular levels. Both rat primary peritoneal mesothelial cells (PMCs) and human PMCs were used for analysis in vitro. Several molecular biological techniques were applied to uncover the potential mechanisms of ligustrazine in preventing PPA. And molecular docking and site-directed mutagenesis assay were used to predict the binding sites of ligustrazine with PPARγ. The bioinformatics analysis was further applied to identify the key pathway in the pathogenesis of PPA. Besides, PPA rodent models were prepared and developed to evaluate the novel ligustrazine nanoparticles in vivo. Ligustrazine could significantly suppress hypoxia-induced PMC functions, such as restricting the production of profibrotic cytokines, inhibiting the expression of migration and adhesion-associated molecules, repressing the expression of cytoskeleton proteins, restricting hypoxia-induced PMCs to obtain myofibroblast-like phenotypes, and reversing ECM remodeling and EMT phenotype transitions by activating PPARγ. The antagonist GW9662 of PPARγ could restore the inhibitory effects of ligustrazine on hypoxia-induced PMC functions. The inhibitor KC7F2 of HIF-1α could repress hypoxia-induced PMC functions, and ligustrazine could downregulate the expression of HIF-1α, which could be reversed by GW9662. And the expression of HIF-1α inhibited by ligustrazine was dramatically reversed after transfection with si-SMRT. The results showed that the benefit of ligustrazine on PMC functions is contributed to the activation of PPARγ on the transrepression of HIF-1α in an SMRT-dependent manner. Molecular docking and site-directed mutagenesis tests uncovered that ligustrazine bound directly to PPARγ, and Val 339/Ile 341 residue was critical for the binding of PPARγ to ligustrazine. Besides, we discovered a novel nanoparticle agent with sustained release behavior, drug delivery efficiency, and good tissue penetration in PPA rodent models. Our study unravels a novel mechanism of ligustrazine in preventing PPA. The findings indicated that ligustrazine is a potential strategy for PPA formation and ligustrazine nanoparticles are promising agents for preclinical application.

The Inhibitory Effects of Naringin in a Rat Model of Postoperative Intraperitoneal Adhesion Formation.

Background Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification of effective preventative measures or treatments is of great importance. In this study, the substantial potential of naringin (NG) to reduce peritoneal adhesions was validated in a rat model. Materials and Methods A rat peritoneal adhesion model was established by abrasion of the cecum and its opposite intraperitoneal region under aseptic surgical conditions. After the operation, three groups of NG-treated rats were given 2 mL of NG by gavage at different concentrations (40, 60, or 80 mg/kg/d). The sham, control, and hyaluronan (HA) groups were given equal volumes of normal saline daily. On the 8th day, all rats were sacrificed 30 min after the administration of an activated carbon solution (10 mL/kg) by oral gavage. Intraperitoneal adhesion formation was adequately evaluated by necropsy, hematoxylin and eosin (HE) staining, Sirius red staining, immunofluorescence staining, enzyme-linked immunosorbent assays, and reactive oxygen species (ROS) probes. The gastrointestinal dynamics of the rats were assessed on the basis of a small intestinal charcoal powder propulsion test and the detection of motilin and gastrin levels in serum. Results Intraperitoneal adhesions were markedly reduced in the group of rats receiving high-dose NG. Compared with the control group, the high-dose NG group showed clear reductions in inflammatory reactions, oxidative stress, collagen deposition, and fibroblast formation in the adhesion tissue and enhanced gastrointestinal dynamics (P < 0.05). Conclusion NG alleviated the severity of intraperitoneal adhesions in a rat model by reducing inflammation, oxidative stress, collagen deposition, and fibroblast formation, highlighting the potential of NG as a drug candidate to prevent postoperative peritoneal adhesion formation.

Prevention of postoperative adhesions of the peritoneum

On the basis of experiments with rabbits, Lhnberg (Arch. F. Gynk., B. 115, H. 3, 1922) came to the conclusion that a harmless, easily tolerated animal substance that prevents the formation of postoperative peritoneal adhesions is liquid, ether-extracted human fat administered intraperitoneally to a rabbit in an amount of about 10 cubic meters.

Nintedanib, a multitarget tyrosine kinase inhibitor, suppresses postoperative peritoneal adhesion formation in a rat model

BackgroundNintedanib is an antifibrotic agent approved by the United States Food and Drug Administration for the treatment of lung fibrosis. This study aimed to evaluate the efficacy of nintedanib for the prevention of postoperative peritoneal adhesion formation in a rat model. MethodsEighteen female Sprague-Dawley rats underwent peritoneal ischemic button creation to induce peritoneal adhesion formation and were randomly allocated to receive 1 mL saline, 50 mg/kg nintedanib, or 100 mg/kg nintedanib by gavage once daily for 7 days. Peritoneal adhesion evaluation and histological and immunochemical examinations were performed on postoperative day 7. Twelve additional Sprague-Dawley rats underwent ileal resection and anastomosis and were randomized to receive saline or 100 mg/kg nintedanib by gavage once daily for 7 days. Anastomotic bursting pressure was assessed on postoperative day 7. ResultsAll rats survived until death 7 days after surgery without complications. Peritoneal adhesion incidence, quality, and tenacity were lower in both nintedanib groups than in the saline group (P < .01), but no differences were found between the 2 nintedanib groups (P > .05). Histological and immunochemical results demonstrated less inflammation, fibrosis, collagen, and cell proliferation and fewer myofibroblasts in the ischemic buttons treated with 50 mg/kg or 100 mg/kg nintedanib than in those treated with saline (P < .01), but no difference was found between the 2 nintedanib groups (P > .05). Anastomotic bursting pressures were not significantly different between the saline and nintedanib groups (P > .05). ConclusionNintedanib is effective for the prevention of postoperative peritoneal adhesion formation in a rat model.

Efficacy of Virgin Olive Oil in Preventing Postoperative Peritoneal Adhesions

Postoperative peritoneal adhesions (PPA) can be formed by any damage to mesothelial cells of peritoneum. Many methods were used to prevent the formation of PPA. Our purpose is to appraise the efficiency of virgin olive oil on PPA before and after formed traumatic peritoneal adhesions. A total of thirty-two rats were divided into four equal groups. Group1 (sham group): Virgin olive oil was applied intraperitoneally. Group2 (control group): Adhesion model was created. Group3: After the adhesion model was created, virgin olive oil was applied to the caecum. Group4: After applying caecum with virgin olive oil, the adhesion model was created. The experiment ended on day 10. Macroscopic and histopathological assessments were made. Compared with Group2 there was a statistically significant reduction in PPA in Group 3 and Group4 results (P &amp;lt; 0.001). Any statistically significant difference was found between Group 3 and Group4 (P &amp;gt; 0.05). Considering our results, we believe that virgin olive oil can reduce the formation of PPA when it has been applied before or after surgical trauma by its anti-inflammation and hydroflotation effects.

Deletion of Calponin 2 Reduces the Formation of Postoperative Peritoneal Adhesions

Aim of the study: Postoperative peritoneal adhesions are a common cause of morbidity after surgery, resulting in multiple complications. Macrophage-mediated inflammation and myofibroblast differentiation after tissue injury play central roles in the pathogenesis and progression of adhesion formation. Calponin 2 is an actin cytoskeleton regulatory protein in endothelial cells, macrophages and fibroblasts that are key players in the development of fibrosis. Deletion of calponin 2 has been shown to attenuate inflammatory arthritis, atherosclerosis and fibrocalcification of the aortic valves. The present study investigated the effect of calponin 2 deletion on attenuating the formation of peritoneal adhesions in a mouse model for potential use as a new therapeutic target. Materials and methods: Sterile surgical procedures under general anesthesia were used on paired wild type (WT) and calponin 2 knockout (KO) mice to generate mild injury on the cecal and abdominal wall peritonea. Three and seven days post-operation, the mice were compared postmortem for the formation of peritoneal adhesions. Tissues at the adhesion sites were examined with histology and immunofluorescent studies for macrophage and myofibroblast activations. Results: Quantitative scoring demonstrated that calponin 2 KO mice developed significantly less postoperative peritoneal adhesions than that in WT mice. Calponin 2 deletion resulted in less infiltration of F4/80+ macrophages at the adhesion sites with less myofibroblast differentiation and collagen deposition than WT controls. Conclusions: The data show that deletion of calponin 2 effectively reduces postoperative peritoneal adhesion, presenting a novel molecular target for clinical prevention.

The Effect of Extractum Cepae, Heparin Sodium, and Allantoin in Experimental Peritoneal Adhesion

The purpose of the study is to investigate the effects of extractum cepae (EC), heparin sodium (HS), and allantoin (AA) on postoperative peritoneal adhesion (PPA) prevention. Forty-eight rats were allocated into six groups (n = 8). PPA was performed by Harris method. In group 1, no additional procedure was done. Abdominal cavity was washed with normal saline in group 2, EC in group 3, HS in group 4, AA in group 5, and EC-HS-AA mixture (EHA-m) in group 6. On the 21st postoperative day, PPA was scored with Nair adhesion score and examined for fibrosis histopathologically and hydroxy-proline levels (OHP) biochemically. Macroscopically, PPA was decreased in groups 2, 4, and 6 compared to groups 1, 3, and 5 (p < 0.05) and decreased in group 2 compared to other groups (p < 0.05). Histopathologically, fibrosis was decreased in groups 2, 4, and 6 compared to other groups and decreased in group 2 compared to other groups (p < 0.05). Tissue OHP level was decreased in groups 2, 3, 4, and 5 compared to groups 1 and 6 (p < 0.05). Tissue OHP level was decreased in group 6 compared to group 1, but the difference was not statistically significant. PPA formation decreases with normal saline, HS and EHA-m, whereas increases with EC and AA both macroscopically and microscopically. Although HS and EHA-m seem to have adhesion prevention effect, washing the intestines with saline seems to be more effective.

Effects of Glycerol and Sodium Pentaborate Formulation on Prevention of Postoperative Peritoneal Adhesion Formation.

Background Postoperative peritoneal adhesions (PPA) are a serious problem for abdominal surgery. An effective remedy has not been found yet. New formulation of glycerol and sodium pentaborate may be able to solve the problem. Method Female Wistar albino rats were randomly assigned into four equal groups. The adhesion model was created on the caecum anterior wall and covered with 2 ml 0.9% NaCl, 3% glycerol, 3% sodium pentaborate, and 3% glycerol plus 3% sodium pentaborate solutions in the groups, respectively. Two weeks later, the rats were sacrificed. PPA were graded macroscopically and microscopically. Results Total adhesion scores of the 3% glycerol + 3% sodium pentaborate group were statistically different from the other groups for macroscopic and also microscopic evaluations (p < 0.001). Conclusion 3% glycerol plus 3% sodium pentaborate as a new formulation has preventive effects on PPA with a synergistic mechanism.

Sodium aescinate significantly suppress postoperative peritoneal adhesion by inhibiting the RhoA/ROCK signaling pathway

BackgroundAlthough mechanical barriers and modern surgical techniques have been developed to prevent postoperative adhesion formation, high incidence of adhesions still represents an important challenge in abdominal surgery. So far, there has been no available therapeutic drug in clinical practice. PurposeIn this study, we explored the efficacy of sodium aescinate (AESS) treatment against postoperative peritoneal adhesions, the potential molecular mechanism was also investigated. Study design and methodsSixty male Sprague-Dawley rats were randomly divided into 6 groups for the study: the blank, vehicle, positive control and three AESS administration groups (0.5, 1 and 2 mg/kg/d, intravenous administration for 7 days). Adhesions were induced by discretely ligating peritoneal sidewall. An IL-1β-induced HMrSV5 cell model was also performed to explore possible functional mechanism. ResultsThe results indicated that the incidence and severity of peritoneal adhesions were significantly lower in the AESS-treated groups than that in the vehicle and positive control group. AESS-treated groups showed that the secretion, activity, and expression of tPA in rat peritoneum were notably increased. The FIB levels in rat plasma were decreased. The immunohistochemical staining analysis demonstrated that collagen I and α-SMA deposition were significantly attenuated in AESS-treated peritoneal tissues. Besides, we found that AESS treatment reduced the protein levels of p-MYPT1. To further explore the mechanisms of AESS, both activator and inhibitors of RhoA/ROCK pathway were employed in this study. It was found that AESS-induced up-regulation of tPA was reversed by activator of ROCK, but the effects of ROCK inhibitors were consistent with AESS. ConclusionTaken together, the findings of in vivo and in vitro experiments proved that AESS could significantly suppress postoperative peritoneal adhesion formation through inhibiting the RhoA/ROCK signaling pathway. Our researches provide important pharmacological basis for AESS development as a potential therapeutic agent on peritoneal adhesions.

NPPB prevents postoperative peritoneal adhesion formation by blocking volume-activated Cl- current.

5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) is a non-specific chloride channel blocker. Peritoneal adhesion is an inevitable complication of abdominal surgery and remains an important clinical problem, leading to chronic pain, intestinal obstruction, and female infertility. The aim of this study is to observe the effects of NPPB on peritoneal adhesions and uncover the underlying mechanism. The formation of postoperative peritoneal adhesions was induced by mechanical injury to the peritoneum of rats. MTT assay and wound-healing assay were used to evaluate proliferation and migration of primary cultured adhesion fibroblasts (AFB) respectively. Whole-cell chloride currents were measured using a fully automated patch-clamp workstation. Cell volume changes were monitored by light microscopy and video imaging. Our results demonstrated that NPPB could significantly prevent the formation of peritoneal adhesion in rats and inhibit the proliferation of AFB in a concentration-dependent manner. NPPB also reduced the migration of AFB cells with an IC50 of 53.09 μM. A 47% hypotonic solution successfully activated the ICl,vol in AFB cells. The current could be blocked by extracellular treatment with NPPB. Moreover, 100 μM NPPB almost completely eliminated the capacity of regulatory volume decrease (RVD) in these cells. These data indicate that NPPB could prevent the formation of postoperative peritoneal adhesions. The possible mechanism may be through the inhibition of the proliferation and migration of AFB cells by modulating ICl,vol and cell volume. These results suggest a potential clinical use of NPPB for preventing the formation of peritoneal adhesions.

Current controversies in tubal disease, endometriosis, and pelvic adhesion

Reproductive surgery for proximal and distal tubal occlusion, as well as for reversal of tubal ligation, may be an alternative or an adjunct to IVF. Surgery for adenomyosis and endometriosis, including endometriomas, may be considered for the treatment of infertility and/or pelvic pain but carries the risks of surgical complications and diminished ovarian reserve. A greater understanding of the pathogenesis of postoperative peritoneal adhesion formation is needed to develop more effective preventive measures to optimize the clinical results of surgery.

Long-term outcomes of pure olive oil to prevent postoperative peritoneal adhesions in rats

Aim: Postoperative peritoneal adhesion (PPA) that occur after abdominopelvic surgery are the current problems of surgeons. The aim of this study was to investigate the effect of pure olive oil in preventing PPA.Methods: Thirty-two rats were randomly divided into four groups: (1) Sham group: 5 ml pure olive oil was injected percutaneously into the peritoneal cavity without laparotomy, (2) Adhesion group: A standard adhesion model was formed on jejunum, ileum and caecum. (3) Adhesion + olive oil: A standard adhesion model was formed on jejunum, ileum and caecum. Subsequently the area on jejunum, ileum and caecum was covered with 5 ml of pure olive oil. (4) Olive oil + adhesion: The area on jejunum, ileum and caecum was covered with 5 ml of pure olive oil. Subsequently the standard adhesion model was formed on this area. Four weeks later, abdominal cavities of rats were examined for PPA, using Evan’s adhesion classification and Zühlke’s histopathological grade scales.Results: PPA was not found in Group 1 in which olive oil was injected intraperitoneally. PPA was present in all rats in Group 2. Microscopic adhesion scores in Group 3 and 4 were significantly lower than Group 2. The collagen fiber fractions were significantly lower and there was a significant decrease in fibrosis. There was no statistically significant difference in microscopic adhesion scores in Group 3 compared to Group 4.Conclusion: We found that antiinflammation, tissue regeneration and hydroflotation effect of pure olive oil decreased PPA formation in rats by maintaining a long lasting effect on the wounded peritoneal surface. Thus olive oil, a cheap and easy to obtain product, can be used in cases of PPA in surgery clinics.

Developmental endothelial locus-1 prevents development of peritoneal adhesions in mice

Postoperative peritoneal adhesions, fibrous bands formed in the peritoneal cavity following surgery, represent a common, challenging and costly problem faced by surgeons and patients, for which effective therapeutic options are lacking. Since aberrant inflammation is one of the key mechanisms underlying peritoneal adhesion formation, here we set out to study the role of developmental endothelial locus-1 (Del-1), which has been recently identified as an endogenous inhibitor of inflammation, in the formation of postoperative peritoneal adhesions using a mouse model of peritoneal adhesions induced by ischemic buttons. Del-1-deficient mice had a higher incidence of adhesions, and their adhesions had higher quality and tenacity scores. Del-1 deficiency also led to enhanced inflammation mediators and collagen production. Finally, Del-1 supplementation decreased the incidence and severity of postoperative peritoneal adhesions. Taken together, these results indicate a protective role for Del-1 in postoperative peritoneal adhesion formation.

The role of oral fluvastatin on postoperative peritoneal adhesion formation in an experimental rat model

Background: Postoperative peritoneal adhesions are a momentousness complication after abdominal surgery. Although varied means have been used to prevent and treat adhesions, the effects have not been satisfactory. Fluvastatin, a HMG-CoA reductase inhibitors, exhibits a variety of pharmacological effects. Aim of this study was to evaluate the effect of fluvastatin on postoperative peritoneal adhesion formation.Methods: Seventy-five male Wistar rats weighting 220–250g were randomly assigned equally to three groups. Group A was given sham operation without treatment, Group B was the model group in which postoperative peritoneal adhesion model was created without medication, and Group C was given oral fluvastatin treatment after postoperative peritoneal adhesion model created. After laparotomy on day 7, macroscopic and pathological assessment were evaluated, IL-1β and t-PA in plasma were performed to measure, and tissue samples were taken to measure MMP-9 protein.Results: There were significant differences between the groups on adhesion grade (p < .05), IL-1β content of the plasma and t-PA activity of the adhesions (p < .05). The grading of adhesion demonstrated significant differences between all groups. The levels of the IL-1β content of plasma, t-PA activity and MMP-9 of adhesion showed pivotal changes in Group B compared with Group A and C, while the difference between Group A and C was not statistically significant.Conclusion: Oral fluvastatin application could reduce formation of intra-abdominal adhesion by promoting expression of MMP-9 level, lowering the levels of IL-1β and increasing the activity of t-PA after abdominal surgery.

Intraperitoneal administration of rosuvastatin prevents postoperative peritoneal adhesions by decreasing the release of tumor necrosis factor.

ObjectivesThe purpose of this experimental study was to demonstrate the reduction of peritoneal adhesions formation in rats after intraperitoneal administration of rosuvastatin, due to its anti-inflammatory effect.MethodPeritoneal adhesions were induced in 120 Wistar-Bratislava rats divided into 4 groups (n=30), using a parietal and visceral (cecal) abrasion model. Group I was designated as control group; in group II, a saline solution was administered intraperitoneally; in groups III and IV, a single dose of rosuvastatin solution, 10 mg/kg and 5 mg/kg respectively, was injected intraperitoneally. The serum values of tumor necrosis factor (TNF-α) and interleukin-1 (IL-1α) were determined on day 1 and day 7 postoperatively (ELISA). Macroscopic assessment of the peritoneal adhesions was conducted on day 14.ResultsRosuvastatin therapy induced a significant decrease of tumor necrosis factor serum levels in groups III and IV, on day 1 and day 7 (p<0.01). Intraperitoneal administration of rosuvastatin correlated with a decrease of mean interleukin-1α levels on postoperative day 1 in groups III (p=0.0013) and IV (p=0.00011), but not on day 7, where the differences were no longer statistically significant (p=0.8) The reduction of postoperative peritoneal adhesions in the experimental rat model is supported by the anti-inflammatory effect of rosuvastatin, mediated mainly by the tumor necrosis factor.ConclusionsRosuvastatin prevents the formation of postoperative peritoneal adhesions in rats. This effect may be linked to the inhibition of proinflammatory cytokines release in the early stages of adhesions formation. The present study suggests that rosuvastatin may be an efficient pharmacological agent in the prevention of postoperative peritoneal adhesions development, and requires further studies as it has a promising application value.