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

Hdl Handle:
http://hdl.handle.net/10675.2/785
Title:
Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats
Authors:
Elmarakby, Ahmed A.; Faulkner, Jessica; Baban, Babak; Sullivan, Jennifer C.
Abstract:
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-b 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.
Citation:
Int J Hypertens. 2012 Feb 26; 2012:957235
Issue Date:
26-Feb-2012
URI:
http://hdl.handle.net/10675.2/785
DOI:
10.1155/2012/957235
PubMed ID:
22518298
PubMed Central ID:
PMC3299363
Type:
Article
ISSN:
2090-0392
Appears in Collections:
Department of Oral Biology: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorElmarakby, Ahmed A.en_US
dc.contributor.authorFaulkner, Jessicaen_US
dc.contributor.authorBaban, Babaken_US
dc.contributor.authorSullivan, Jennifer C.en_US
dc.date.accessioned2012-10-26T20:30:44Z-
dc.date.available2012-10-26T20:30:44Z-
dc.date.issued2012-02-26en_US
dc.identifier.citationInt J Hypertens. 2012 Feb 26; 2012:957235en_US
dc.identifier.issn2090-0392en_US
dc.identifier.pmid22518298en_US
dc.identifier.doi10.1155/2012/957235en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/785-
dc.description.abstractThe 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-b 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.en_US
dc.rightsCopyright © 2012 Ahmed A. Elmarakby et al.en_US
dc.subjectResearch Articleen_US
dc.titleInduction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Ratsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3299363en_US
dc.contributor.corporatenameDepartment of Oral Biology-
dc.contributor.corporatenameDepartment of Medicine-

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