Free radical damage as a biomarker of bladder dysfunction after partial outlet obstruction and reversal.
OBJECTIVE
To investigate the use of free-radical generation as a result of protein carbonylation and nitrotyrosination to characterize the level of bladder dysfunction after partial bladder outlet obstruction (PBOO) and reversal.


METHODS
We surgically created PBOO in male New Zealand White rabbits; after 4 weeks of PBOO, one group of six rabbits was assessed, while the PBOO was relieved in two additional groups of six rabbits each that were assessed at 4 and 8 weeks after relieving the PBOO. Six sham-operated rabbits served as controls. Sedated rabbits were assessed by cystometry and the bladders were then removed for contractile, histological and molecular studies. Western blotting was used to determine the level of carbonylation and nitrotyrosination at the protein level.


RESULTS
The PBOO group had significant decreases in the contractile responses to field stimulation, ATP, carbachol and KCl. The responses to all forms of stimulation increased significantly at 4 weeks after reversal, and further increased to near normal levels by 8 weeks. Similarly, compliance and cystometric values also returned to near normal values after reversal. The hypertrophied smooth muscle of the obstructed bladders regressed to near-normal size. There was a significant increase in the level of carbonylation and nitrotyrosination after PBOO, and a progressive decrease in the 4-week reversal groups, nearing control values by 8 weeks.


CONCLUSIONS
Significantly increased carbonylation and nitrotyrosination levels after PBOO correlated with the severe dysfunction in the obstructed rabbits. Similarly, decreased levels of oxidation and nitration correlated with the functional recovery after reversal.
Lin
Wei-Yu
WY
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
Guven
Ahmet
A
Juan
Yung-Shun
YS
Neuman
Paul
P
Whitbeck
Catherine
C
Chichester
Paul
P
Kogan
Barry
B
Levin
Robert M
RM
Mannikarottu
Anita
A
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D050050:Protein Carbonylation / Q000502:physiology; D011817:Rabbits; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D001743:Urinary Bladder / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*
D015415:Biomarkers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species