Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis.
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.
Kanai
Anthony J
AJ
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. ajk5@pitt.edu
Zeidel
Mark L
ML
Lavelle
John P
JP
Greenberger
Joel S
JS
Birder
Lori A
LA
de Groat
William C
WC
Apodaca
Gerard L
GL
Meyers
Susan A
SA
Ramage
Richard
R
Epperly
Michael W
MW
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
D008081:Liposomes; D011837:Radiation-Protective Agents; D013482:Superoxide Dismutase