Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-kappaB.
OBJECTIVE
Diabetic nephropathy is a debilitating disease that leads to end-stage renal failure in the Western world. Hyperglycemia is the initiating factor in several chronic diabetic complications which mediates increased oxidative stress and eventually the increased production of vasoactive factors and extracellular matrix proteins. We hypothesized that curcumin, a potent antioxidant, might be beneficial in preventing the development of diabetic nephropathy because this compound has been shown to inhibit p300, a histone acetyltransferase that plays a role in regulating gene expression through its interaction with the transcription factor nuclear factor-kappaB.


METHODS
To test this hypothesis, male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. These animals were subsequently treated with curcumin for a period of 1 mo.


RESULTS
Real-time reverse transcriptase polymerase chain reaction analyses showed that diabetes-induced upregulation of vasoactive factors (endothelial nitric oxide synthase and endothelin-1), transforming growth factor-beta1 and extracellular matrix proteins (fibronectin and extradomain-B-containing fibronectin) in the kidneys. These changes were associated with increased oxidative stress, mesangial expansion, and p300 and nuclear factor-kappaB activity that were prevented with curcumin treatment.


CONCLUSIONS
These beneficial effects of curcumin were mediated through the inhibition of p300 and nuclear factor-kappaB.
Chiu
Jane
J
Department of Pathology, University of Western Ontario, London, Ontario, Canada.
Khan
Zia A
ZA
Farhangkhoee
Hana
H
Chakrabarti
Subrata
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D030024:Curcuma; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors*; D019332:Endothelin-1 / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000975:Antioxidants; D019332:Endothelin-1; D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D016212:Transforming Growth Factor beta; D019001:Nitric Oxide Synthase; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D003474:Curcumin