Document Detail


Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis.
MedLine Citation:
PMID:  12426235     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Urinary bladder cystitis occurs in patients receiving radiation therapy for pelvic tumors. Radiation-induced formation of superoxide radicals is believed to damage the urothelium, exposing the underlying bladder smooth muscle to urine, culminating in nerve irritation and muscle dysfunction. We tested whether overexpression of MnSOD could decrease superoxide levels and protect the bladder from radiation damage. Pelvic irradiation led to sloughing of urothelial umbrella cells, with decreased transepithelial resistance, increased water and urea permeabilities, and increased expression of inducible nitric oxide synthase. Six months after irradiation, cystometrograms showed elevated intravesical pressures and prolonged voiding patterns. However, urothelia transfected with the MnSOD transgene recovered from radiation injury more rapidly, and detrusor function was much closer to that of control bladders than irradiated bladders without the transgene. We conclude that MnSOD gene therapy is protective, which could lead to its use in mitigating radiation cystitis and preventing dysfunction of the urinary bladder.
Authors:
Anthony J Kanai; Mark L Zeidel; John P Lavelle; Joel S Greenberger; Lori A Birder; William C de Groat; Gerard L Apodaca; Susan A Meyers; Richard Ramage; Michael W Epperly
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  283     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-11     Completed Date:  2002-12-17     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1304-12     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. ajk5@pitt.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cystitis / etiology*,  prevention & control*
Female
Gene Therapy*
Liposomes
Pelvis / radiation effects
Plasmids
Radiation Injuries / complications*
Radiation-Protective Agents*
Rats
Rats, Sprague-Dawley
Superoxide Dismutase / genetics*
Urinary Bladder / pathology,  radiation effects
Grant Support
ID/Acronym/Agency:
DK-43955/DK/NIDDK NIH HHS; DK-48217/DK/NIDDK NIH HHS; HL-57985/HL/NHLBI NIH HHS; HL-60132/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 0/Radiation-Protective Agents; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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