Cellular stress-response modulators in the acute rat model of peritoneal dialysis.
Cytotoxicity of peritoneal dialysis fluids (PDF) not only results in cellular injury, but also induces heat-shock proteins (HSP), the main effectors of the cellular stress response. This study investigated effects of modulation of mesothelial HSP expression on peritoneal membrane integrity during acute PDF exposure. In the acute in vivo rat model of peritoneal dialysis (PD), either the HSP coinducer indomethacin or the HSP suppressor quercetin was added to standard PDF (CAPD 3, Fresenius, Germany). HSP-72 expression, number of detached mesothelial cells, and peritoneal protein loss were evaluated at the end of a 4-h dwell time. Compared with pure PDF exposure, addition of indomethacin resulted in increased expression of mesothelial HSP-72, reduced mesothelial cell exfoliation, and reduced peritoneal protein loss. Addition of quercetin resulted in decreased expression of HSP-72, increased mesothelial cell exfoliation, and higher peritoneal protein loss. Differences were statistically significant between indomethacin-treated and quercetin-treated rats. Mesothelial HSP expression was related to markers of peritoneal membrane integrity upon in vivo PDF exposure, consistent with HSP-mediated cytoprotection. These data clearly demonstrate the potential for clinically feasible pharmacologic interventions with the cellular stress response as a novel therapeutic approach to improve PD outcome.
Boehm
Michael
M
Department of Pediatric and Adolescent Medicine, Medical University of Vienna, AKH Wien, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Bergmeister
Helga
H
Kratochwill
Klaus
K
Vargha
Regina
R
Lederhuber
Hans
H
Aufricht
Christoph
C
D000818:Animals; D015314:Dialysis Solutions / Q000737:chemistry / Q000633:toxicity; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D010530:Peritoneal Dialysis; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism
D015314:Dialysis Solutions; D050884:HSP72 Heat-Shock Proteins; D014404:Tubulin; D011794:Quercetin; D007213:Indomethacin
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