Changes in end products of nitric oxide in urine and induction of nitric oxide synthase expression in urinary bladder during intravesical instillations of IFN-alpha2b.
Interferon-alpha2b (IFN-alpha2b) is being used intravesically for preventing recurrence and progression of superficial transitional cell carcinoma of the bladder. However, its mechanism of action when instilled intravesically is not yet elucidated. We monitored end products of nitric oxide (NO) in urine in 12 bladder cancer patients undergoing intravesical instillations of IFN-alpha2b. Urine end products of NO levels rose gradually after each instillation, reaching a peak value after the third instillation. Although the patients continued their treatment for 5 more weeks, no further alteration was observed. Inducible nitric oxide synthase (iNOS) expression was immunohistochemically evaluated in urinary bladder biopsy specimens before and after IFN-alpha2b instillations. It was shown that IFN-alpha2b induced urothelial iNOS expression, with subsequent oxidative stress. The peroxynitrite (ONOO-) formed from the combination of NO with superoxide (O2-) provides important clues in the role of ONOO- as a causative factor in the antineoplastic action of IFN-alpha2b.
Mitropoulos
Dionisios
D
1st Department of Urology, Athens Medical School, Athens, Greece. dmp@otenet.gr
Deliconstantinos
George
G
Adamakis
Ioannis
I
Zervas
Anastasios
A
Karakaidos
Panagiotis
P
Gorgoulis
Vassilis G
VG
D000283:Administration, Intravesical; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000652:urine*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000652:urine; D011994:Recombinant Proteins; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II