title: Oxidative Stress and Nuclear Factor κB (NF-κB) Increase Peritoneal Filtration and Contribute to Ascites Formation in Nephrotic Syndrome.
abstract: Water accumulation in the interstitium (edema) and the peritoneum (ascites) of nephrotic patients is classically thought to stem from the prevailing low plasma albumin concentration and the decreased transcapillary oncotic pressure gradient. However, several clinical and experimental observations suggest that it might also stem from changes in capillary permeability. We addressed this hypothesis by studying the peritoneum permeability of rats with puromycin aminonucleoside-induced nephrotic syndrome. The peritoneum of puromycin aminonucleoside rats displayed an increase in the water filtration coefficient of paracellular and transcellular pathways, and a decrease in the reflection coefficient to proteins. It also displayed oxidative stress and subsequent activation of NF-κB. Scavenging of reactive oxygen species and inhibition of NF-κB prevented the changes in the water permeability and reflection coefficient to proteins and reduced the volume of ascites by over 50%. Changes in water permeability were associated with the overexpression of the water channel aquaporin 1, which was prevented by reactive oxygen species scavenging and inhibition of NF-κB. In conclusion, nephrotic syndrome is associated with an increased filtration coefficient of the peritoneum and a decreased reflection coefficient to proteins. These changes, which account for over half of ascite volume, are triggered by oxidative stress and subsequent activation of NF-κB.
authors.affiliation: From the Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL8228, Centre de Recherche des Cordeliers, F-75006, Paris, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: Udwan
authors.affiliation: From the Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL8228, Centre de Recherche des Cordeliers, F-75006, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Brideau
authors.affiliation: From the Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL8228, Centre de Recherche des Cordeliers, F-75006, Paris, France, the Department of Pediatric Nephrology, Centre hospitalier Universitaire (CHU) Robert Debré Assistance Publique-Hôpitaux de Paris (APHP), Université Paris 7 Denis Diderot, F-75020 Paris, France, and.
authors.forename: Marc
authors.initials: M
authors.lastname: Fila
authors.affiliation: From the Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL8228, Centre de Recherche des Cordeliers, F-75006, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Edwards
authors.affiliation: the Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, CH-3010 Bern, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vogt
authors.affiliation: From the Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL8228, Centre de Recherche des Cordeliers, F-75006, Paris, France, alain.doucet@crc.jussieu.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D001201:Ascites / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D011692:Puromycin Aminonucleoside / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496022:Aqp1 protein, rat; D016328:NF-kappa B; D051398:Aquaporin 1; D011692:Puromycin Aminonucleoside
keywords: NF-kappa B (NF-KB); albumin; oxidative stress; permeability; water channel