Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction

Background. Unilateral ureteral obstruction (UUO) is a well-established exp erimental model of renal injury leading to interstitial fibrosis. The molec ular and cellular mechanism(s) of interstitial fibrosis in UUO kidney is be ginning to be elucidated. Oxidative stress has been implicated in the patho genesis of various forms of renal injury; however, little is known about it s 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 NE- carboxymethyl-lysine (CML) in the kidneys after ureteral obstruction. CML i s an integrative biomarker of the cumulative protein damage induced by glyc oxidation. Heme oxygenase-l (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 ob served in the periglomerular and peritubular interstitium two days after ur eteral obstruction. Conclusions. These results strongly suggested the presence of increased oxi dative stress in the interstitium of UUO kidneys. The oxidative stress and the formation of various kind of biological active oxidative products in th e interstitium are supposed to play significant roles in UUO kidney.