Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis

• Published in: American journal of physiology. Renal physiology Vol. 283; no. 6; pp. F1304 - F1312
• Main Authors: Kanai, Anthony J, Zeidel, Mark L, Lavelle, John P, Greenberger, Joel S, Birder, Lori A, de Groat, William C, Apodaca, Gerard L, Meyers, Susan A, Ramage, Richard, Epperly, Michael W
• Format: Journal Article
• Language: English
• Published: United States 01.12.2002
• Subjects: Animals; Cystitis - etiology; Cystitis - prevention & control; Female; Genetic Therapy; Liposomes; Pelvis - radiation effects; Plasmids; Radiation Injuries - complications; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; Superoxide Dismutase - genetics; Urinary Bladder - pathology; Urinary Bladder - radiation effects
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00228.2002

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.