Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction.
BACKGROUND
Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to interstitial fibrosis. The molecular and cellular mechanism(s) of interstitial fibrosis in UUO kidney is beginning to be elucidated. Oxidative stress has been implicated in the pathogenesis of various forms of renal injury; however, little is known about its involvement in the setting of ureteral obstruction.


METHODS
To investigate the possible involvement of oxidative stress in the obstructive nephropathy, we studied the occurrence and distribution of Nepsilon-carboxymethyl-lysine (CML) in the kidneys after ureteral obstruction. CML is an integrative biomarker of the cumulative protein damage induced by glycoxidation. Heme oxygenase-1 (HO-1) mRNA and protein expression, which is a sensitive and reliable indicator of oxidative stress, were also examined.


RESULTS
CML immunoreactivity was found in the interstitium of UUO kidneys 10 days after the onset ureteral obstruction. HO-1 mRNA was up-regulated as early as 12 hours after ureteral obstruction. HO-1 immunoreactivity was observed in the periglomerular and peritubular interstitium two days after ureteral obstruction.


CONCLUSIONS
These results strongly suggested the presence of increased oxidative stress in the interstitium of UUO kidneys. The oxidative stress and the formation of various kind of biological active oxidative products in the interstitium are supposed to play significant roles in UUO kidney.
Kawada
N
N
The First Department of Medicine, Osaka University of Medicine, School of Health and Sport Sciences, Osaka University, Japan.
Moriyama
T
T
Ando
A
A
Fukunaga
M
M
Miyata
T
T
Kurokawa
K
K
Imai
E
E
Hori
M
M
D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; D012333:RNA, Messenger; C048496:N(6)-carboxymethyllysine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D008239:Lysine