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

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 prot...

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Main Authors: Ahmed A. Elmarakby, Jessica Faulkner, Babak Baban, Jennifer C. Sullivan
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:International Journal of Hypertension
Online Access:http://dx.doi.org/10.1155/2012/957235
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author Ahmed A. Elmarakby
Jessica Faulkner
Babak Baban
Jennifer C. Sullivan
author_facet Ahmed A. Elmarakby
Jessica Faulkner
Babak Baban
Jennifer C. Sullivan
author_sort Ahmed A. Elmarakby
collection DOAJ
description 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-β 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.
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spelling doaj-art-8177b037449d4f5e8e865f6dff0b946a2025-08-20T03:35:07ZengWileyInternational Journal of Hypertension2090-03842090-03922012-01-01201210.1155/2012/957235957235Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive RatsAhmed A. Elmarakby0Jessica Faulkner1Babak Baban2Jennifer C. Sullivan3Department of Oral Biology, Georgia Health Sciences University, Augusta, GA 30912, USADepartment of Oral Biology, Georgia Health Sciences University, Augusta, GA 30912, USADepartment of Oral Biology, Georgia Health Sciences University, Augusta, GA 30912, USADepartment of Medicine, Georgia Health Sciences University, Augusta, GA 30912, USAThe 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-β 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.http://dx.doi.org/10.1155/2012/957235
spellingShingle Ahmed A. Elmarakby
Jessica Faulkner
Babak Baban
Jennifer C. Sullivan
Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
International Journal of Hypertension
title Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
title_full Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
title_fullStr Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
title_full_unstemmed Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
title_short Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
title_sort induction of hemeoxygenase 1 reduces renal oxidative stress and inflammation in diabetic spontaneously hypertensive rats
url http://dx.doi.org/10.1155/2012/957235
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