Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats

被引：22

作者：

Elmarakby, Ahmed A. ^{[1
]}

Faulkner, Jessica ^{[1
]}

Baban, Babak ^{[1
]}

Sullivan, Jennifer C. ^{[2
]}

机构：

[1] Georgia Hlth Sci Univ, Dept Oral Biol, Augusta, GA 30912 USA

[2] Georgia Hlth Sci Univ, Dept Med, Augusta, GA 30912 USA

来源：

INTERNATIONAL JOURNAL OF HYPERTENSION | 2012年 / 2012卷

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1155/2012/957235

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The renoprotective mechanisms of hemeoxygenase-1 (HO-1) in diabetic nephropathy remain to be investigated. We hypothesize that HO-1 protects the kidney from diabetic insult via lowering renal oxidative stress and inflammation. We used control and diabetic SHR with or without HO-1 inducer cobalt protoporphyrin (CoPP) treatment for 6 weeks. Urinary albumin excretion levels were significantly elevated in diabetic SHR compared to control and CoPP significantly attenuated albumin excretion. Immuno-histochemical analysis revealed an elevation in TGF-beta staining together with increased urinary collagen excretion in diabetic versus control SHR, both of which were reduced with CoPP treatment. Renal oxidative stress markers were greater in diabetic SHR and reduced with CoPP treatment. The increase in renal oxidative stress was associated with an elevation in renal inflammation in diabetic SHR. CoPP treatment also significantly attenuated the markers of renal inflammation in diabetic SHR. In vitro inhibition of HO with stannous mesoporphyrin (SnMP) increased glomerular NADPH oxidase activity and inflammation and blocked the anti-oxidant and anti-inflammatory effects of CoPP. These data suggest that the reduction of renal injury in diabetic SHR upon induction of HO-1 are associated with decreased renal oxidative stress and inflammation, implicating the role of HO-1 induction as a future treatment of diabetic nephropathy.

引用

页数：11

共 52 条

[1] Heme oxygenase: the key to renal function regulation [J].

Abraham, Nader G. ;

Cao, Jian ;

Sacerdoti, David ;

Li, Xiaoying ;

Drummond, George .

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2009, 297 (05) :F1137-F1152

[2] Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats - Possible role in renoprotection [J].

Aizawa, T ;

Ishizaka, N ;

Taguchi, J ;

Nagai, R ;

Mori, I ;

Tang, SS ;

Ingelfinger, JR ;

Ohno, M .

HYPERTENSION, 2000, 35 (03) :800-806

[3] NAD(P)H OXIDASES IN CORONARY ARTERY DISEASE [J].

Arora, Sarika ;

Vaishya, Richa ;

Dabla, P. K. ;

Singh, Bhawna .

ADVANCES IN CLINICAL CHEMISTRY, VOL 50, 2010, 50 :65-86

[4] Prevention of loss of renal function over time in patients with diabetic nephropathy [J].

Barnett, A .

AMERICAN JOURNAL OF MEDICINE, 2006, 119 (05) :40S-47S

[5] Adipocyte Heme Oxygenase-1 Induction Attenuates Metabolic Syndrome in Both Male and Female Obese Mice [J].

Burgess, Angela ;

Li, Ming ;

Vanella, Luca ;

Kim, Dong Hyun ;

Rezzani, Rita ;

Rodella, Luigi ;

Sodhi, Komal ;

Canestraro, Martina ;

Martasek, Pavel ;

Peterson, Stephen J. ;

Kappas, Attallah ;

Abraham, Nader G. .

HYPERTENSION, 2010, 56 (06) :1124-U246

[6] Upregulation of Heme Oxygenase-1 Combined with Increased Adiponectin Lowers Blood Pressure in Diabetic Spontaneously Hypertensive Rats through a Reduction in Endothelial Cell Dysfunction, Apoptosis and Oxidative Stress [J].

Cao, Jian ;

Drummond, George ;

Inoue, Kazuyoshi ;

Sodhi, Komal ;

Li, Xiao Ying ;

Omura, Shinji .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2008, 9 (12) :2388-2406

[7] Reversibility of established diabetic glomerulopathy by anti-TGF-β antibodies in dbldb mice [J].

Chen, S ;

Igleasias-de la Cruz, MC ;

Jim, B ;

Hong, SW ;

Isono, M ;

Ziyadeh, FN .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 300 (01) :16-22

[8] Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice [J].

Chow, F. Y. ;

Nikolic-Paterson, D. J. ;

Ma, F. Y. ;

Ozols, E. ;

Rollins, B. J. ;

Tesch, G. H. .

DIABETOLOGIA, 2007, 50 (02) :471-480

[9] Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice [J].

Chow, FY ;

Nikolic-Paterson, DJ ;

Ozols, E ;

Atkins, RC ;

Rollin, BJ ;

Tesch, GH .

KIDNEY INTERNATIONAL, 2006, 69 (01) :73-80

[10] Intercellular adhesion molecule-1 deficiency is protective against nephropathy in type 2 diabetic db/db mice [J].

Chow, FY ;

Nikolic-Paterson, DJ ;

Ozols, E ;

Atkins, RC ;

Tesch, GH .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (06) :1711-1722

← 1 2 3 4 5 6 →