Urinary oxidative stress markers closely reflect the efficacy of candesartan treatment for diabetic nephropathy.
OBJECTIVE
It has been reported that urinary oxidative stress markers are higher in diabetic patients with proteinuria. We performed the present study to elucidate the relationship between urinary excretion of oxidative stress markers, albumin excretion, and histological changes, and to confirm the potential utility of oxidative stress markers for clinical treatment.


METHODS
Diabetic db/db mice or nondiabetic db/m mice were administered candesartan (10 mg/kg/day) or hydralazine (50 mg/kg/day) for 18 weeks.


RESULTS
Thirty-week-old male db/db mice treated with control vehicle revealed elevated urinary excretion and immunohistological levels of 8-hydroxydeoxyguanosine in glomeruli when compared to db/m mice. Treatment with candesartan, but not hydralazine, reduced these values to levels in db/m mice. Increased mesangial expansion, urinary excretion of albumin and 8-isoprostane, and glomerular immunohistological levels of nitrotyrosine in db/db mice were also decreased markedly by candesartan but not hydralazine. Interestingly, correlations between levels of albumin and oxidative stress markers in urine were very high, even when groups undergoing long-term (44 weeks) treatment were included (correlation coefficient 0.767 with respect to 8-hydroxydeoxyguanosine, 0.888 with respect to 8-isoprostane).


CONCLUSIONS
It is anticipated that urinary concentrations of oxidative stress markers will be direct barometers of glomerulus-derived oxidative stress and glomerular injury in diabetic nephropathy.
Yoshida
Shin-ichiro
S
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine and School of Medicine, Yokohama, Japan.
Hashimoto
Tatsuo
T
Kihara
Minoru
M
Imai
Nozomi
N
Yasuzaki
Hiroaki
H
Nomura
Kouichirou
K
Kiuchi
Yoshihiro
Y
Tamura
Kouichi
K
Ishigami
Tomoaki
T
Hirawa
Nobuhito
N
Toya
Yoshiyuki
Y
Kitamura
Hitoshi
H
Umemura
Satoshi
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000419:Albuminuria / Q000652:urine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D001713:Biphenyl Compounds; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D003920:Diabetes Mellitus / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004195:Disease Models, Animal; D006830:Hydralazine / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000652:urine
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006830:Hydralazine; C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine; C081643:candesartan