Peritoneal Adhesion Formation Research Articles

Comparison of the effect of Everolimus, Prednisolone, and a combination of both on experimentally induced peritoneal adhesions in rats

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

NETworking for Health and in Disease: Neutrophil Extracellular Traps in Pediatric Surgical Care.

This comprehensive review examines the role of Neutrophil Extracellular Traps (NETs) in pediatric surgery. Focusing on NET formation, functions, and implications, this study highlights their dual impact in infection control and contribution to tissue damage after surgery. It covers the role of NET formation in a range of pediatric conditions including immunothrombosis, formation of peritoneal adhesions, appendicitis, burns, gallstones, tumors, and necrotizing enterocolitis (NEC). The results underscore the significance of NETs in fighting infections and their association with complications like sepsis and delayed wound healing. The breakdown products of NETs as a diagnostic tool of the clinical course of acute appendicitis will also be discussed. Understanding NET formation in the pathophysiology can potentially help to find new therapeutic approaches such as the application of DNase and elastase inhibitors to change the clinical course of various diseases in pediatric surgery such as improvement of wound healing, adhesion formation, NEC, and many more.

D-limonene inhibits peritoneal adhesion formation in rats via anti-inflammatory, anti-angiogenic, and antioxidative effects.

The aim of this research was to investigate the effects of D-limonene on decreasing post-operative adhesion in rats and to understand the mechanisms involved. Peritoneal adhesions were induced by creating different incisions and excising a 1 × 1cm section of the peritoneum. The experimental groups included a sham group, a control group in which peritoneal adhesions were induced without any treatment, and two treatment groups in which animals received D-limonene with dosages of 25 and 50mg/kg after inducing peritoneal adhesions. Macroscopic examination of adhesions showed that both treatment groups had reduced adhesion bands in comparison to the control group. Immunohistochemical assessment of TGF-β1, TNF-α, and VEGF on day 14 revealed a significant increment in the level of immunopositive cells for the mentioned markers in the control group, whereas administration of limonene in both doses significantly reduced levels of TGF-β1, TNF-α, and VEGF (P < 0.05). Induction of peritoneal adhesions in the control group significantly increased TGF-β1, TNF-α, and VEGF on days 3 and 14 in western blot evaluation, while treatment with limonene significantly reduced TNF-α level on day 14 (P < 0.05). Moreover, VEGF levels in both treatment groups significantly reduced on days 3 and 14. In the control group, a significant increment in the levels of MDA and NO and a notable decline in the levels of GPX, CAT was observed (P < 0.05). Limonene 50 group significantly reduced MDA level and increased GPx and CAT levels on day 14 (P < 0.05). In summary, D-limonene reduced adhesion bands, inflammatory cytokines, angiogenesis, and oxidative stress.

A novel barrier membrane with long-term ROS scavenging function for complete prevention of postoperative adhesion

Local oxidative stress induced by surgical trauma has been recognized as one of pathogenesis for postsurgical adhesion tissue formation. Herein, tannic acid (TA) based metal-phenolic networks (MPNs) was assembled via chelating with Fe3+, and acted as a novel bio-filler for nanofibrous polycaprolactone (PCL) barrier membrane to endow it with reactive oxygen species (ROS) scavenging capacity. By chelating with Fe3+, the release of TA could last for more than 20 days, rendering the membrane with continuous ROS scavenging capacity. The modified membrane could effectively inhibit fibroblasts adhesion and proliferation, as well as immune cells recruitment, infiltration, and expression of pro-inflammatory cytokines. Consequently, a complete prevention of peritoneal adhesion formation was obtained in a rat model of sidewall defect-cecum abrasion, far better than commercial Poly lactic acid (PLA) membrane. Systematic biological mechanism investigations revealed that the enhanced anti-adhesion function was mainly ascribed to its robust ROS scavenging capacity, through which the PI3K-Akt signaling pathway was blocked, leading to repress of downstream NF-κB-TGFβ1-SMAD signaling pathway, finally inhibiting the bioactivity of fibroblasts and immune cells. This work provided a new strategy for the design of advanced barrier membrane, demonstrated its efficacy and mechanism on preventing postoperative adhesion, holding great promise for future clinical application.

Farnesol remodels the peritoneal cavity immune environment influencing Candida albicans pathogenesis during intra-abdominal infection

ABSTRACT Candida albi c ans is a lifelong member of the mycobiome causing mucosal candidiasis and life-threatening, systemic, and intra-abdominal disease in immunocompromised and transplant patients. Despite the clinical importance of intra-abdominal candidiasis with mortality rates between 40% and 70%, the contribution of fungal virulence factors and host immune responses to disease has not been extensively studied. Secretion of the quorum-sensing molecule, farnesol, acts as a virulence factor for C. albicans during systemic infection, while inducing local, protective innate immune responses in oral models of infection. Previously, we reported that farnesol recruits macrophages to the peritoneal cavity in mice, suggesting a role for farnesol in innate immune responses. Here, we expand on our initial findings, showing that farnesol profoundly alters the peritoneal cavity microenvironment promoting innate inflammation. Intra-peritoneal injection of farnesol stimulates rapid local death of resident peritoneal cells followed by recruitment of neutrophils and inflammatory macrophages into the peritoneal cavity and peritoneal mesothelium associated with an early increase in chemokines followed by proinflammatory cytokines. These rapid inflammatory responses to farnesol significantly increase morbidity and mortality of mice with intra-abdominal candidiasis associated with increased formation of peritoneal adhesions, despite similar rates of fungal clearance from the peritoneal cavity and retro-peritoneal organs. C. albicans ddp3Δ/ddp3Δ knockout and reconstituted strains recapitulate these findings. This indicates that farnesol may be detrimental to the host during intra-abdominal infections. Importantly, our results highlight a need to understand how C. albicans virulence factors modulate the host immune response within the peritoneum, an exceedingly common site of Candida infection.

Neutrophil extracellular traps and DNases orchestrate formation of peritoneal adhesions

Peritoneal adhesions are poorly understood but highly prevalent conditions that can cause intestinal obstruction and pelvic pain requiring surgery. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the molecular processes of their formation still remain elusive. We performed murine models and analyzed human samples to monitor the formation of adhesions and the treatment with DNases. Various molecular analyses were used to evaluate the adhesions. The experimental peritoneal adhesions of the murine models and biopsy material from humans are largely based on neutrophil extracellular traps (NETs). Treatment with DNASE1 (Dornase alfa) and the human DNASE1L3 analog (NTR-10), significantly reduced peritoneal adhesions in experimental models. We conclude that NETs serve as essential scaffold for the formation of adhesions; DNases interfere with this process. Herein, we show that therapeutic application of DNases can be employed to prevent the formation of murine peritoneal adhesions. If this can be translated into the human situation requires clinical studies.

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.

Smart hydrogels delivered by high pressure aerosolization can prevent peritoneal adhesions

Postoperative peritoneal adhesions occur in the majority of patients undergoing intra-abdominal surgery and are one of the leading causes of hospital re-admission. There is an unmet clinical need for effective anti-adhesive biomaterials, which can be applied evenly across the damaged tissues. We examined three different responsive hydrogel types, i.e. a thermosensitive PLGA-PEG-PLGA, a pH responsive UPy-PEG and a shear-thinning hexapeptide for this purpose. More specifically, their potential to be homogeneously distributed in the peritoneal cavity by high pressure nebulization and prevent peritoneal adhesions was evaluated.Solutions of each polymer type could be successfully nebulized while retaining their responsive gelation behavior in vitro and in vivo. Furthermore, none of the polymers caused in vitro toxicity on SKOV3-IP2 cells. Following intraperitoneal administration, both the PLGA-PEG-PLGA and the hexapeptide hydrogels resulted in local inflammation and fibrosis and failed in preventing peritoneal adhesions 7 days after adhesion induction. In contrast, the pH sensitive UPy-PEG formulation was well tolerated and could significantly reduce the formation of peritoneal adhesions, even outperforming the commercially available Hyalobarrier® as positive control. To conclude, local nebulization of the bioresponsive UPy-PEG hydrogel can be considered as a promising approach to prevent postsurgical peritoneal adhesions.

Carbon monoxide (CO) derived from the CO-releasing molecule CORM-2 reduces peritoneal adhesion formation in a rat model.

Although low-dose carbon monoxide (CO) administration has been shown to have an anti-fibrotic effect in various fibrotic diseases, its effects on peritoneal adhesion (PA), one of the postoperative complications, are not elucidated. In this study, the effect of CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2) administration on the formation of PA and the underlying factors of its potential effect were investigated. After the induction of PA, rats were divided into four groups with 8 rats in each group. The rats received either (i) dimethyl sulfoxide:saline solution (1:10) as a vehicle, (ii) 2.5mg/kg CORM-2, (iii) 5mg/kg CORM-2, or (iv) inactive (i) CORM (iCORM) intragastrically every day for a duration of 7days. PA was not induced in rats (n = 8) designated as sham controls. Gross, histological, immunohistochemical and quantitative real-time polymerase chain reaction analyses were performed to evaluate the effectiveness of CORM-2 administration. Gross analysis showed that CORM-2 administration reduced PA formation compared to rats treated with vehicle. Histological and immunohistochemical examinations showed that increased collagen deposition, myofibroblast accumulation, microvessel density, and M1 macrophage count in the peritoneal fibrosis area of vehicle-treated rats decreased following CORM-2 treatments. PCR analyses showed that CORM-2 treatments decreased hypoxia-induced Hif1a, profibrotic Tgfb1, ECM components Col1a1 and Col3a1, collagen degradation suppressor Timp1, fibrinolysis inhibitor Serpine1, and pro-inflammatory Tnf mRNA expressions, while increasing the M2 macrophage marker Arg1 mRNA expression. These results suggested that CORM-2 administration reduces PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis and fibrogenesis.

Practice of Peritoneal Adhesions in Osteopathic Medicine: Part 2.

Peritoneal adhesions are an unwanted and frequent event following abdominal surgery, with a response rate that can reach 100%. The adhesions can be symptomatic, becoming a source of pain and discomfort for the patient, or asymptomatic, with possible chronic or acute visceral dysfunction. The article reviews what the diagnostic strategies are and discusses what could be the causes that lead to chronic pain in the presence of adhesions. The text reports the knowledge of the literature on the manual treatment of adhesions and illustrates possible symptoms that are not easily recognized by the clinician. To conclude, the article proposes osteopathic manual approaches derived from clinical experience and from what has been explained about the formation of peritoneal adhesions. Research must make further efforts to identify not only the causes triggering the formation of peritoneal neogenesis but also seek the most appropriate non-invasive treatments to help the patient.

Can we predict peritoneal adhesions formation after cesarean delivery?

To examine demographic and obstetrical factors that are associated with adhesion formation following cesarean delivery. We conducted a population-based study that included all women over 18 years og age who underwent two cesarean deliveries between the years 1988 and 2016 in a large tertiary medical center. We excluded women with adhesions already diagnosed during the first cesarean delivery, history of other abdominal or pelvic surgery, history of pelvic infection or pelvic inflammatory disease, history of endometriosis and history of uterine Müllerian anomalies. In addition, women with a classical or T-shaped uterine incision, non-singleton pregnancies, and fetal chromosomal or structural abnormalities were excluded. During the study period, 32.6% (n = 2283) of women were diagnosed with peritoneal adhesions during the second cesarean delivery. Factors found to be significantly associated with peritoneal adhesions were maternal age 35 years or older at the first cesarean delivery, Bedouin Arab ethnicity, composite of intrapartum and postpartum infectious morbidity, and cesarean deliveries that were performed after the onset of labor. In contrast, having a previous vaginal birth was found to be protective. Our results suggest that a woman's characteristics at her first cesarean delivery and her obstetrical history may be predictive of the likelihood of adhesion formation.

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.

Different routes of administering EW-7197 versus EW-7197⋅HBr for preventing peritoneal adhesion in a rat model.

The relatively low aqueous solubility of EW-7197 that was administered orally may have affected the desired concentration in the systemic circulation for treating peritoneal adhesion. Thisexperimental study aimed to compare the efficacy of different routes of administering EW-7197 (2-fluoro-N-[(5-[6-methylpyridin-2-yl]-4-[(1,2,4)triazolo(1,5-a)pyridin-6-yl]-1H-imidazol-2-yl)methyl]aniline) and EW-7197·hydrobromide (HBr), with improved aqueous solubility, for inhibiting peritoneal adhesion in a rat model. After peritoneal adhesion induction, 30 male Sprague-Dawley rats were randomly divided into 5 groups with 6 rats in each: group A, sham control; group B, orally administered 25 mg/kg of EW-7197·HBr for 7 days; group C, locally administered 25 mg/kg of EW-7197·HBr; group D, orally administered 20 mg/kg of EW-7197 for 7 days; and group E, locally administered 20 mg/kg of EW-7197. Gross examination, histologic staining (hematoxylin and eosin and Masson's trichrome), and immunohistochemical analyses (Ki-67 and α-smooth muscle actin marker [α-SMA]) were performed to evaluate the efficacy of both drugs. All procedures were technically successful. All treatment groups, except for group C, showed significantly reduced incidence, quality, tenacity, fibrosis, and collagen deposition scores and lowered expressions of Ki-67- and α-SMA-positive cells compared with group A. When comparing between groups, all scores were significantly lower in group B than in group C (all P < .001), whereas no significant difference was noted in any of the scores between groups D and E and groups B and E (all P > .05). Orally administering EW-7197·HBr and both orally and locally administering EW-7197 significantly prevented peritoneal adhesion formation, and orally administering EW-7197·HBr was the most effective overall.

Peritoneal lavage with Glycyrrhiza glabra is effective in preventing peritoneal adhesion in a rat model.

Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities. Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model. Male Wistar rats weighing 200-250g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-ꞵ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines. We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-β(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001-0.05), fibrosis (P < 0.001-0.05), and oxidative (P < 0.001-0.05) factors, while propagating the anti-oxidant marker (P < 0.001-0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300µg/ml (P > 0.05). G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.

The preventive effect of omega-3 fish oil on the formation of peritoneal adhesions.

&lt;br&gt;&lt;b&gt;Introduction:&lt;/b&gt; Postoperative peritoneal adhesions that form after abdominal surgery still continue to exist as an unresolved health problem.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of the study is to examine whether omega-3 fish oil has a preventive effect on postoperative peritoneal adhesions.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; Twenty-one female Wistar albino rats were separated into 3 groups (sham, control and experimental), each consisting of 7 rats. In the sham group, only laparotomy was performed. In both the control and experimental group rats, the right parietal peritoneum and cecum were traumatised to form petechiae. Following this procedure, the abdomen was irrigated with omega-3 fish oil in the experimental group. The rats were re-explored on the 14&lt;sup&gt;th&lt;/sup&gt; postoperative day and any adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; None of the rats that were administered omega-3 fish oil developed macroscopic postoperative peritoneal adhesions (P = 0.005). The omega-3 fish oil formed an anti-adhesive lipid barrier on the injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in the control group rats, while foreign body reactions were common in the omega-3 rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in the omega-3 rats than in the control rats (P = 0.004).&lt;/br&gt; &lt;br&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.&lt;/br&gt.

HPLC/MS characterization of Syzygium aromaticum L. and evaluation of its effects on peritoneal adhesion: Investigating the role of inflammatory cytokines, oxidative factors, and fibrosis and angiogenesis biomarkers.

The dried flower bud of Syzygium aromaticum L. (S. aromaticum) (Myrtaceae), cloves, have been used for their analgesic and anti-inflammatory activities. Peritoneal adhesion (PA) is the most common complication of abdominal and pelvic surgeries, which causes significant adverse effects and severe economic burden. The present study aimed to evaluate the preventive effect of S. extract (SAE) on PA formation in a rat model. Male Wistar 8-week-old rats were randomly divided into sham, control (received vehicle), and treatment (0.25%, 0.5%, and 1% w/v of SAE) groups. The adhesion and related factors were examined using the Nair scoring system and immunological and biochemical kits for the levels of inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], growth factors [transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)], oxidative [nitric oxide (NO) and malondialdehyde (MDA)], and anti-oxidative [glutathione (GSH)] factors. Our results figured out that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly increased, but the GSH level was decreased in the control group compared to the sham group (p< 0.001-0.05). On the other hand, the 0.25% SAE group had a lower adhesion score, and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly decreased compared with the vehicle group, and the level of GSH was increased (p< 0.001-0.05). SAE could efficiently reduce adhesion score and regulate inflammatory cytokines, oxidative and anti-oxidative factors, and biomarkers of fibrosis and angiogenesis. Therefore, clove extract can be considered a potential candidate for PA management.

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.

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion.

A peritoneal adhesion (PA) is a fibrotic tissue connecting the abdominal or visceral organs to the peritoneum. The formation of PAs can induce a variety of clinical diseases. However, there is currently no effective strategy for the prevention and treatment of PAs. Damage to peritoneal mesothelial cells (PMCs) is believed to cause PAs by promoting inflammation, fibrin deposition, and fibrosis formation. In the early stages of PA formation, PMCs undergo mesothelial–mesenchymal transition and have the ability to produce an extracellular matrix. The PMCs may transdifferentiate into myofibroblasts and accelerate the formation of PAs. Therefore, the aim of this review was to understand the mechanism of action of PMCs in PAs, and to offer a theoretical foundation for the treatment and prevention of PAs.

Activating SIRT3 in peritoneal mesothelial cells alleviates postsurgical peritoneal adhesion formation by decreasing oxidative stress and inhibiting the NLRP3 inflammasome

Peritoneal adhesions (PAs) are a serious complication of abdominal surgery and negatively affect the quality of life of millions of people worldwide. However, a clear molecular mechanism and a standard therapeutic strategy for PAs have not been established. Here, we developed a standardized method to mimic the pathological changes in PAs and found that sirtuin 3 (SIRT3) expression was severely decreased in adhesion tissues, which was consistent with our bioinformatics analysis and patient adhesion tissue analysis. Thus, we hypothesized that activating SIRT3 could alleviate postsurgical PAs. Sirt3-deficient (Sirt3−/−) mice exhibited many more PAs after standardized abdominal surgery. Furthermore, compared with wild-type (Sirt3+/+) mice, Sirt3-deficient (Sirt3−/−) mice showed more prominent reactive oxygen species (ROS) accumulation, increased levels of inflammatory factors, and exacerbated mitochondrial damage and fragmentation. In addition, we observed NLRP3 inflammasome activation in the adhesion tissues of Sirt3−/− but, not Sirt3+/+ mice. Furthermore, mesothelial cells sorted from Sirt3−/− mice exhibited impaired mitochondrial bioenergetics and redox homeostasis. Honokiol (HKL), a natural compound found in several species of the genus Magnolia, could activate SIRT3 in vitro. Then, we demonstrated that treatment with HKL could reduce oxidative stress and the levels of inflammatory factors and suppress NLRP3 activation in vivo, reducing the occurrence of postsurgical PAs. In vitro treatment with HKL also restored mitochondrial bioenergetics and promoted mesothelial cell viability under oxidative stress conditions. Taken together, our findings show that the rescue of SIRT3 by HKL may be a new therapeutic strategy to alleviate and block postsurgical PA formation.

Comparison of Oral Sirolimus, Prednisolone, and Combination of Both in Experimentally Induced Peritoneal Adhesion.

Peritoneal adhesion formation is a challenging postoperative complication. We aim to evaluate the effect of orally administered sirolimus, prednisolone, and their combination to prevent this entity. Eighty female albino underwent intraperitoneal injection of 3mL of 10% sterile talc solution to induce peritoneal adhesion, and were subsequently and randomly divided into four groups (each n=20); including a control group; 1mg/kg oral prednisolone daily in the morning; 0.1mg/kg oral sirolimus daily; and a combination group which received both drugs, with the same dosage. On the 29th day, abdominal cavities were explored, and classification was done based on Nair classification. All rats were healthy on the 29th day, in which exploration was performed. The rats in the control group had extensive intra-abdominal adhesions, while 17 (85%) rats in the control group had substantial adhesion; however, the prednisolone, sirolimus, and combination group had lesser adhesion formation. Also, 14 (70%) rats of prednisolone group, 13 (65%) of sirolimus group, and 16 (80%) of combination group had insubstantial adhesion. The decrease in the grade of peritoneal adhesion bands was highly significant in the combination group (P>0.001). The combination of sirolimus and prednisolone was effective for preventing peritoneal adhesions in rats.