title: Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis.
abstract: 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.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. ajk5@pitt.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kanai
authors.forename: Mark L
authors.initials: ML
authors.lastname: Zeidel
authors.forename: John P
authors.initials: JP
authors.lastname: Lavelle
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: Lori A
authors.initials: LA
authors.lastname: Birder
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Gerard L
authors.initials: GL
authors.lastname: Apodaca
authors.forename: Susan A
authors.initials: SA
authors.lastname: Meyers
authors.forename: Richard
authors.initials: R
authors.lastname: Ramage
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
mesh_terms: D000818:Animals; D003556:Cystitis / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D015316:Genetic Therapy; D008081:Liposomes; D010388:Pelvis / Q000528:radiation effects; D010957:Plasmids; D011832:Radiation Injuries / Q000150:complications*; D011837:Radiation-Protective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics*; D001743:Urinary Bladder / Q000473:pathology / Q000528:radiation effects
chemical_list: D008081:Liposomes; D011837:Radiation-Protective Agents; D013482:Superoxide Dismutase