Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD

Douma, Caroline E.; Waart, Dirk R. de; Zemel, Désirée; Struijk, Dirk G.; Krediet, Raymond T.

doi:10.1093/ndt/16.4.803

Cited by 19 publications

(15 citation statements)

References 23 publications

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“…16,17 Interestingly, whereas the inhibition of prostaglandin synthesis, by intraperitoneal administration of indomethacin, results in a decrease of hyperpermeability to macromolecules during peritonitis, it has no effect on permeability in clinically stable and uncomplicated PD patients. 20,21 These findings suggest that only the augmented prostaglandins, probably those produced by the inducible COX-2, are involved in peritoneal transport dysfunction.…”

Section: Discussionmentioning

confidence: 98%

Cyclooxygenase-2 Mediates Dialysate-Induced Alterations of the Peritoneal Membrane

Aroeira¹,

Lara‐Pezzi²,

Loureiro³

et al. 2009

Journal of the American Society of Nephrology

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During peritoneal dialysis (PD), exposure of the peritoneal membrane to nonphysiologic solutions causes inflammation, ultimately leading to altered structure and function. Myofibroblasts, one of the cell types that contribute to dysfunction of the peritoneal membrane, can originate from mesothelial cells (MCs) by epithelial-to-mesenchymal transition (EMT), a process that has been associated with an increased rate of peritoneal transport. Because cyclooxygenase-2 (COX-2) is induced by inflammation, we studied the role of COX-2 in the deterioration of the peritoneal membrane. We observed that nonepithelioid MCs found in peritoneal effluent expressed higher levels of COX-2 than epithelioid MCs. The mass transfer coefficient for creatinine correlated with MC phenotype and with COX-2 levels. Although COX-2 was upregulated during EMT of MCs in vitro, COX-2 inhibition did not prevent EMT. In a mouse model of PD, however, COX-2 inhibition with Celecoxib resulted in reduced fibrosis and in partial recovery of ultrafiltration, outcomes that were associated with a reduction of inflammatory cells. Furthermore, PD fluid with a low content of glucose degradation products did not induce EMT or COX-2; the peritoneal membranes of mice treated with this fluid showed less worsening than mice exposed to standard fluid. In conclusion, upregulation of COX-2 during EMT may mediate peritoneal inflammation, suggesting COX-2 inhibition as a potential strategy to ameliorate peritoneal deterioration in PD patients.

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Section: Discussionmentioning

confidence: 98%

Cyclooxygenase-2 Mediates Dialysate-Induced Alterations of the Peritoneal Membrane

Aroeira¹,

Lara‐Pezzi²,

Loureiro³

et al. 2009

Journal of the American Society of Nephrology

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“…Although limited studies performed to establish efficacy in humans have had mixed results (33)(34)(35), evidence generated from patients with peritoneal inflammation due to peritoneal dialysis, animal models of peritoneal inflammation, and in vitro studies, support the use of agents to suppress peritoneal eicosanoid production in the peritoneal cavity following infection or surgical trauma. Intraperitoneal (IP) administration of indomethacin in continuous ambulatory peritoneal dialysis patients during peritonitis has been reported to decrease the intrinsic permeability of the peritoneum to macromolecules without effectively altering other peritoneal functional parameters (36). In addition, IP administration of indomethacin following peritoneal bacterial challenge enhances leukocyte migration and peritoneal permeability to protein and dialysate concentrations of PGE2, PGF1α and IL-8.…”

Section: Inflammatory Mediators and Adhesion Formationmentioning

confidence: 99%

Peritoneal molecular environment, adhesion formation and clinical implication

Chegini¹

2002

Front Biosci

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Whether induced by infection, inflammation, ischemia, and/or surgical injury, peritoneal adhesions are the leading cause of pelvic pain, bowel obstruction and infertility. It is clear that while postsurgical peritoneal wounds heal without adhesions in some patients, others develop severe scarring from seemingly equal procedures; in addition, in the same patient, adhesions can develop at one surgical site and not in another. The mechanisms underlying the predisposition to form adhesions as well as their site specificity are completely unknown. However, a large number of intraperitoneal surgical procedures are performed each day in the USA, and thus many patients are at risk of developing postoperative adhesions. Therefore, understanding of adhesion formation at the molecular level is essential and in the absence of such information, attempts to prevent patients from developing adhesions will remain an empirical process. The unprecedented advancement in molecular biology during the past decade has led to the identification of many biologically active molecules with the potential of regulating inflammatory and immune responses, angiogenesis and tissue remodeling, events that are central to normal peritoneal wound healing and adhesion formation. Although, the insight into their importance in the development of tissue fibrosis has substantially increased, their major roles in peritoneal biological functions and adhesion formation remain at best speculative. This article reviews the clinical implications of adhesions and attempts to highlight some of the key molecules i.e. growth factors, cytokines, chemokines, proteases and extracellular matrix, that are recognized to regulate inflammation, fibrinolysis, angiogenesis, and tissue remodeling, events that are central to peritoneal wound repair and adhesion formation. Finally, the article discusses the potential application and site specific delivery of several active compounds that are developed to alter the local inflammatory and immune response i.e., cytokine/chemokine network, targeted gene delivery and development of a new generation of biomaterials to prevent adhesion formation. Such understanding of peritoneal biology not only assist us to better manage patients with adhesion, but also those with endometriosis and malignant diseases that affect the peritoneal cavity.

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“…Inhibition of prostanoid production by intraperitoneal administration of indomethacin resulted in lower concentrations of the vasodilating ones, both in animals [30] and humans [31,32], but the effect on peritoneal protein transport was equivocal. Indomethacin in non-peritonitis patients inhibited 6-keto-PGF 1· , but had no effect on peritoneal transport [33]. It follows from these findings that prostaglandins are mainly involved in large pore peritoneal transport during peritonitis only, and have no effect on the regulation of the vascular peritoneal surface area.…”

Section: Peritoneal Transport and Inflammatory Mediators During Peritmentioning

confidence: 78%

Peritoneal Membrane Failure in Peritoneal Dialysis Patients

et al. 2002

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A review is given of the conditions associated with peritoneal membrane failure, and the possible causes. Ultrafiltration failure is the most important manifestation. It is mostly associated with high transport rates of low molecular weight solutes suggesting the presence of a large vascular surface area. Enlargement of the peritoneal surface area can be functional (effective surface area: more perfused microvessels) or anatomic (more microvessels). The former is likely to be present in some patients in the beginning of peritoneal dialysis, and also during peritonitis. The latter can develop in long-term peritoneal dialysis.

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Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD

Cited by 19 publications

References 23 publications

Cyclooxygenase-2 Mediates Dialysate-Induced Alterations of the Peritoneal Membrane

Cyclooxygenase-2 Mediates Dialysate-Induced Alterations of the Peritoneal Membrane

Peritoneal molecular environment, adhesion formation and clinical implication

Peritoneal Membrane Failure in Peritoneal Dialysis Patients

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